SKIN The Journal of Cutaneous Medicine

Real-world safety of spesolimab in generalized pustular psoriasis: Evidence from an expanded access program in Argentina

2024-11-08T14:49:17+00:00

Introduction: Generalized pustular psoriasis (GPP) is a heterogeneous, systemic, neutrophilic, inflammatory disease associated with chronic symptoms and periods of flaring. Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved for the treatment of flares in adult patients with GPP in Argentina (17 Aug 2023).¹ Here, we present safety data from a real-world expanded access program (EAP: 22 Feb 2023–10 Jan 2024) in Argentina which provided early access to spesolimab intravenous (IV) for GPP patients presenting with a flare with no other treatment options.
Methods: Patients (18–75 years old) diagnosed with GPP received a 900mg dose of spesolimab IV for flare treatment, with an optional second dose after 1 week for persistent flare symptoms. Adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were recorded for up to 16 weeks after the last spesolimab infusion.
Results: Six female patients were treated with spesolimab IV (1 dose, n=2; 2 doses, n=4).Mean (standard deviation [SD]) age: 49.3 (11.5) years (range: 30–60 years), mean (SD) body mass index: 28.1 (5.8) kg/m², and mean (SD) follow-up: 3.85 (0.11) months. At baseline, GPP had been diagnosed within ≤1 year (n=2), >1–≤5 years (n=1), and >10 years (n=3). Reported flare triggers were stress (n=2), treatment withdrawal (n=1), heat (n=1), lack of current treatment efficacy (n=1), and unknown (n=1). At baseline, 4 patients had ≥1 comorbidity, including hypertension (n=2), tachycardia, hypothyroidism, chronic gastritis, arthritis, and epilepsy (each n=1). Five patients reported use of ≥1 concomitant medication (including immunosuppressants and corticosteroids) during the EAP; 1 patient had discontinued ustekinumab (biologic). Three patients had signs of plaque psoriasis within the past year and had received treatment for plaque psoriasis; 1 patient had ongoing plaque psoriasis. In total, 4 patients had any AEs (all 4 patients had mild AEs [influenza, catarrh, pruritis, rash, pain] and 1 of these patients also had a moderate AE [headache]). Two drug-related AEs (pruritus and rash) were reported in 1 patient. The hypersensitivity event (rash) was non-serious. There were no reports of SAEs, AESIs, or AEs that led to discontinuation/death.

Conclusion: Spesolimab showed a favorable safety profile in patients with GPP, including patients with comorbidities and those taking concomitant medication. Findings were comparable with a Phase 2a randomized controlled trial in patients with GPP flares (EFFISAYIL 1).

Spesolimab decreases generalized pustular psoriasis (GPP) body surface area (BSA) over time in patients switching from conventional systemic treatments: Results from the EFFISAYIL® 2 trial

2024-11-13T18:50:19+00:00

Generalized pustular psoriasis (GPP) is a chronic inflammatory, potentially life-threatening skin disease. Most patients experience chronic skin symptoms between flares which can lead to significant patient burden. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved in the United States to treat GPP in adults and pediatric patients 12 years of age and older and weighing at least 40 kg. EFFISAYIL^® 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous (SC) spesolimab in GPP. Here, we report the effects on GPP body surface area (BSA) over time in patients switched from a small-molecule systemic therapy at randomization when treated with the FDA approved spesolimab dosing regimen (600 mg loading dose, then 300 mg maintenance dose every 4 weeks) in EFFISAYIL^® 2. Total BSA was determined based on a weighted average of the extent of involvement over 4 main body regions, with head = 10%, upper extremities = 20%, trunk = 30%, and lower extremities = 40%. Total BSA involvement was calculated for each subject at 4 timepoints (baseline, Week 4, Week 16, and Week 48). Data collected closest to the given time points were used by including the effect of potential intravenous spesolimab treatment and subsequent open-label SC spesolimab treatment in patients who experienced a flare. The data were analyzed as observed. Within the FDA approved spesolimab regimen group, the average BSA for patients who stopped a systemic medication for GPP (Total N=22; acitretin = 13, cyclosporine = 7, methotrexate = 1, acitretin/methotrexate = 1) was 11.1 at baseline, decreasing to 8.2 at Week 4, 6.4 at Week 16, and then ending at 3.6 at Week 48. Total BSA involvement decreased over the 48 weeks of the trial in spesolimab-treated patients who stopped an off-label systemic medication for GPP at randomization.

Spesolimab decreases generalized pustular psoriasis (GPP) body surface area (BSA) over time in patients with various lengths of disease history: Results from the EFFISAYIL® 2 trial

2024-11-13T20:41:39+00:00

Generalized pustular psoriasis (GPP) is a chronic inflammatory, potentially life-threatening skin disease. Most patients experience chronic skin symptoms between flares which can lead to significant patient burden. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved in the United States to treat GPP in adults and pediatric patients 12 years of age and older and weighing at least 40 kg. EFFISAYIL^® 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous (SC) spesolimab in GPP. Here, we report the effects on GPP body surface area (BSA) over time in patients diagnosed <5 vs ≥5 years prior to enrollment when treated with the FDA approved spesolimab dosing regimen (600 mg loading dose, then 300 mg maintenance dose every 4 weeks) in EFFISAYIL^® 2. Total BSA was determined based on a weighted average of the extent of involvement over 4 main body regions, with head = 10%, upper extremities = 20%, trunk = 30%, and lower extremities = 40%. Total BSA involvement was calculated for each subject at 4 timepoints (baseline, Week 4, Week 16, and Week 48). Data collected closest to the given time points were used by including the effect of potential intravenous spesolimab treatment and subsequent open-label SC spesolimab treatment in patients who experienced a flare. The data were analyzed as observed. Within the FDA approved regimen spesolimab group, average BSA for patients diagnosed with GPP for <5 years (N=13) was 14.7 at baseline, 15.0 at Week 4, then decreasing to 11.7 at Week 16, and then to 5.0 at Week 48. For patients diagnosed with GPP for ≥ 5 years (N=17) the values were 12.3 at baseline, decreasing to 7.0 at Week 4, increasing slightly to 7.6 at Week 16, and decreasing to 4.1 at Week 48. Total BSA involvement decreased over the 48 weeks of the trial in spesolimab-treated patients regardless of whether they were early (< 5 years) or late (≥ 5 years) in their disease course. This finding demonstrates the efficacy of spesolimab in controlling GPP consistently for patients with various lengths of disease history.

Spesolimab increases the percentage of generalized pustular psoriasis (GPP) patients with clear skin over time as measured by the Physician’s Global Assessment for GPP (GPPGA): Results from the EFFISAYIL® 2 trial

2024-11-13T21:11:08+00:00

Spesolimab decreases generalized pustular psoriasis (GPP) body surface area (BSA) over time: Results from the EFFISAYIL® 2 trial

2024-11-13T21:40:18+00:00

Generalized pustular psoriasis (GPP) is a chronic inflammatory, potentially life-threatening skin disease. Most patients experience chronic skin symptoms between flares which can lead to significant patient burden. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved in the United States to treat GPP in adults and pediatric patients 12 years of age and older and weighing at least 40 kg. EFFISAYIL^® 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous (SC) spesolimab in GPP. Here, we report the effects on GPP body surface area (BSA) over time in patients treated with the FDA approved spesolimab dosing regimen (600 mg loading dose, then 300 mg maintenance dose every 4 weeks) in EFFISAYIL^® 2. Total BSA was determined based on a weighted average of the extent of involvement over 4 main body regions, with head = 10%, upper extremities = 20%, trunk = 30%, and lower extremities = 40%. Total BSA involvement was calculated for each subject at 4 timepoints (baseline, Week 4, Week 16, and Week 48). Data collected closest to the given time points were used by including the effect of potential intravenous spesolimab treatment and subsequent open-label SC spesolimab treatment in patients who experienced a flare. The data were analyzed as observed. Total BSA improved continuously under spesolimab treatment (13.3% at baseline, 10.6% at Week 4, 9.4% at Week 16, ending at 4.5% at Week 48). Continuous treatment with spesolimab SC improved BSA from 13% to 5% at the end of the trial. These findings suggest a role of spesolimab in improving area of involvement as measured by BSA.

Four-weekly dosing intervals with subcutaneous spesolimab appear to be required for optimal prevention of generalized pustular psoriasis flares: Data from the EFFISAYIL® 2 and EFFISAYIL® ON trials

2024-11-13T22:12:31+00:00

Generalized pustular psoriasis (GPP) is a rare chronic skin disease characterized by recurrent, acute, and often life-threatening flares of widespread neutrophilic sterile pustules and systemic inflammation. Spesolimab, an anti-interleukin-36 receptor antibody, is approved in adults and adults and pediatric patients 12 years of age and older and weighing at least 40 kg, as a subcutaneous dosage for treatment of GPP when not experiencing a flare, and as an intravenous dosage for GPP flare treatment. In Effisayil 2, a randomized, placebo-controlled trial (NCT04399837), subcutaneous spesolimab was superior to placebo and well tolerated for flare prevention when administered as a 600-mg subcutaneous loading dose followed by 300 mg every 4 weeks (q4w) over 48 weeks. In Effisayil 2, 3/30 (10.0%) patients receiving subcutaneous spesolimab 300 mg q4w had flares, and there were no flares after Week 4 until the end of the study. We assessed the effect on flare recurrence of a longer (q12w) interval between subcutaneous spesolimab doses in Effisayil 2 and Effisayil ON (NCT03886246), an ongoing open-label extension trial. Flares were defined as a ≥2-point increase in GPP Physician Global Assessment total score with pustulation subscore of ≥2, or intravenous spesolimab or standard of care treatment due to GPP worsening.

In Effisayil 2, 9/31 (29.0%) patients who received subcutaneous spesolimab 300 mg q12w had a flare; of those, 7/9 (77.8%) experienced a flare before their second subcutaneous dose (Week 12), and 5/7 (71.4%) flares occurred during Weeks 4–12, indicating the need for q4w dosing. In Effisayil ON, 36/108 (33.3%) patients who started q12w dosing were either escalated to a q4w regimen (n=24) or experienced a flare (n=12).

These observations suggest that subcutaneous spesolimab 300 mg q4w is the optimal dosing regimen for prevention of GPP flares.

Utilization and Duration of Systemic Corticosteroid Exposure in Atopic Dermatitis Patients After the Introduction of Advanced Therapies: A Population-Based Study From the United States

2024-11-04T16:05:11+00:00

Introduction: Clinical guidelines discourage routine use of systemic corticosteroids (SCS) for the management of atopic dermatitis (AD). However, adherence to these guidelines remain unclear. This is particularly relevant given the availability of advanced systemic treatments, including biologics and JAK inhibitors, for AD. We investigated the utilization and duration of SCS exposure among AD patients after the introduction of advanced therapies.

Methods: Using the U.S. Optum CDM database from 03/2017 to 03/2024, we defined a cohort of AD patients ≥ 12 years old who initiated oral or intramuscular SCS. To increase the likelihood that the SCS treatment was related to AD, we limited the cohort to recently diagnosed AD patients (within the preceding 6 months) without recent diagnoses of immuno-mediated diseases, asthma, osteoarthritis, dorsalgia, gout, bursitis, tendonitis, carpal tunnel, or a history of malignancies, organ transplant or HIV/AIDS. Continuous health insurance enrollment was required for at least 1 year before and after initiating SCS. We followed patients until the end of available data, health insurance discontinuation, or death to determine exposure duration. Exposure time was categorized as short-term (<30 days), medium-term (30-90 days), or long-term (>90 days) based on data observation and clinical experience. Categorical and continuous variables were presented as numbers and percentages or mean and standard deviation values, respectively.

Results: During the study period, 29,994 patients aged 12 years or older with a recent AD diagnosis initiated SCS treatment, representing 20% of eligible AD patients. Most SCS initiators were prescribed oral SCS (80%). Of all users, 67.7% (20,293) received SCS for a short-term period, while 8.5% (2,535) for a medium-term duration, and 23.9% (7,166) for a long-term period. Overall, the average age was 50 (±22) years old. Short-term SCS users had a higher percentage of patients under 30 years old (27%) compared to medium-term (19.7%) and long-term users (16.1%). Patients in all three groups were mostly female (58-60%). At baseline, long-term users received slightly higher prescriptions of biologics (3.3% vs 3.1% and 2.5%) and immunosuppressants (2.6% vs 1.9% and 1.2%) compared to medium-term and short-term users and had higher usage of non-steroidal anti-inflammatory drugs (19.2% vs 15.2% and 13.5%). Dermatologist visits were similar among the three groups, with medium-term users having the highest proportion of encounters (33.9%).

Conclusion: Despite clinical guidelines advising against the use of SCS for AD, they remain widely prescribed, and a relevant proportion of patients are exposed to SCS for extended durations (over 90 days).

Long-Term Maintenance of Optimal Treatment Targets for Skin and Itch Outcomes With Upadacitinib in Moderate-to-Severe Atopic Dermatitis: 140-Week Results From the Phase 3 Measure Up 1 and 2 Studies

2024-11-04T15:52:07+00:00

Introduction: Despite undergoing prolonged systemic therapy, many patients with moderate-to-severe atopic dermatitis (AD) do not achieve optimal targets for skin and itch outcomes as defined by Aiming High in Eczema/AD (AHEAD) recommendations (eg, ≥90% improvement from baseline in Eczema Area and Severity Index [EASI 90] and Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1 [no/minimal itch]). We evaluated long-term maintenance of optimal treatment targets with upadacitinib, an oral selective JAK inhibitor approved for moderate-to-severe AD in adolescents and adults.

Methods: This 140-week interim analysis included adolescents and adults with moderate-to-severe AD who were randomized at baseline to upadacitinib 15 mg (UPA15) or 30 mg (UPA30) in the ongoing, phase 3, double-blind Measure Up 1 and 2 studies. Assessments included the proportion of patients (at the population level) who maintained EASI 90, WP-NRS 0/1, or simultaneous achievement of EASI 90 + WP-NRS 0/1 responses from week 16 (end of the placebo-controlled period) onwards. Data are reported as observed cases with no imputation for missing data.

Results: Among patients who achieved EASI 90 at week 16 (UPA15, n=298; UPA30, n=384), EASI 90 was maintained by 79.8% (UPA15) and 83.7% (UPA30) at week 52, 76.7% (UPA15) and 83.0% (UPA30) at week 100, and 74.0% (UPA15) and 84.2% (UPA30) at week 140. Of patients achieving WP-NRS 0/1 at week 16 (UPA15, n=193; UPA30, n=281), WP-NRS 0/1 was maintained by 69.4% (UPA15) and 72.0% (UPA30) at week 52, 65.6% (UPA15) and 68.4% (UPA30) at week 100, and 62.3% (UPA15) and 66.0% (UPA30) at week 140. Of patients simultaneously achieving EASI 90 + WP-NRS 0/1 at week 16 (UPA15, n=156; UPA30, n=243), maintenance was achieved by 68.1% (UPA15) and 70.8% (UPA30) at week 52, 62.7% (UPA15) and 66.5% (UPA30) at week 100, and 58.7% (UPA15) and 64.4% (UPA30) at week 140. Among patients who did not maintain optimal outcomes, most still achieved clinically meaningful responses.

Conclusion: Most patients maintained optimal skin and itch outcomes through 140 weeks of upadacitinib treatment, demonstrating its potential to provide sustained long-term disease control in atopic dermatitis.

Real-World Effectiveness of Upadacitinib in Moderate‑to‑Severe Atopic Dermatitis (AD): Results From Longitudinal Analyses of the CorEvitas AD Registry

2024-11-04T15:29:25+00:00

Introduction: Clinical trials demonstrated that upadacitinib is efficacious in treating atopic dermatitis (AD). Its real-world effectiveness is less understood. In this study, we investigated the longitudinal real-world outcomes of upadacitinib-treated adults in the CorEvitas AD Registry.

Methods: The CorEvitas AD Registry is a prospective, non-interventional registry of adults diagnosed with AD in the United States and Canada. We evaluated participants enrolled through April 30, 2024 with data available prior to upadacitinib exposure (baseline) and at the six-month follow-up visit, and were receiving upadacitinib at the follow-up visit. Outcomes evaluated include the achievement of: Validated Investigators Global Assessment Scale for Atopic Dermatitis (vIGA-AD^TM) of “clear” or “almost clear” among participants rated “mild” or worse at baseline (vIGA-AD 0/1); Eczema Area and Severity Index improvement of ≥75%/≥90%/100% from baseline (EASI 75/90/100); Peak Pruritus Numeric Rating Scale (PP-NRS) improvement ≥4 among participants with a score ≥4 at baseline (∆PP-NRS≥4); PP-NRS score of 0 or 1 among participants with a score >1 at baseline (PP-NRS 0/1); Dermatology Life Quality Index (DLQI) score improvement ≥4 among participants with a score ≥4 at baseline (∆DLQI≥4); and DLQI score of 0 or 1 among participants with a score >1 at baseline (DLQI 0/1). Simultaneous achievement of both EASI 90 & PP-NRS 0/1 was also assessed. Data were analyzed as observed with no imputation. Safety events were not assessed in this analysis.

Results: The longitudinal analysis included 192 participants (mean age 46.2 years; 57.8% female; 69.8% White; 43.8% prior exposure to dupilumab or tralokinumab; 64.4% receiving 15 mg dose at follow-up visit; mean upadacitinib treatment duration of 6.0 months). More than half achieved clear/almost clear skin (66.1% vIGA-AD 0/1), EASI 75 (69.3%), and EASI 90 (59.2%); 45.3% achieved complete skin clearance (EASI 100). More than 40% reported little-to-no itch (44.4% PP-NRS 0/1) and no impact of AD on quality of life (43.3% DLQI 0/1), and more than half reported meaningful improvements in itch (58.6% ∆PP-NRS≥4) and quality of life (76.0% ∆DLQI≥4). Simultaneous attainment of both EASI 90 & PP-NRS 0/1 was achieved in 46.6% of participants at 6 months.

Conclusions: In the real-world setting, the majority of adults treated and remained on upadacitinib achieved clinically meaningful outcomes in skin lesions, itch, and quality of life, with many achieving complete skin clearance, little-to-no itch, and experiencing no impact of AD on their quality of life. These findings underscore upadacitinib's potential to offer multidimensional relief to patients with AD in everyday clinical practice.

Switching from Dupilumab to Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis and Inadequate Response to Dupilumab: Efficacy and Safety Results from the Phase 3b/4 LEVEL UP Study

2024-10-31T20:23:41+00:00

Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Upadacitinib (UPA), a selective oral Janus kinase (JAK) inhibitor, and dupilumab (DUPI), a monoclonal antibody targeting interleukin-4 and interleukin-13 signaling, are both approved treatments for moderate-to-severe AD. LEVEL UP is a phase 3b/4 efficacy assessor blinded monotherapy study comparing UPA to DUPI for treatment of moderate-to-severe AD in adults and adolescents over a 16-week period (Period 1). Patients not achieving ≥75% improvement in the Eczema Area and Severity Index (EASI 75) from baseline at Week 16 entered an additional 16-week extension phase (Period 2). In Period 2, patients either continued/escalated to UPA 30 mg (UPA/UPA 30) or switched from DUPI to UPA 15 mg (DUPI/UPA), with the potential to escalate to 30 mg based on clinical response. Efficacy for skin and itch outcomes in Period 2 were assessed using observed case analysis while on treatment, without statistical comparisons. Here we report efficacy and safety results for the DUPI/UPA switch group.

A total of 355 patients who did not achieve EASI 75 at Week 16 entered Period 2 of the study (DUPI/UPA, N=208). At Week 32, response rates in the DUPI/UPA group were: 79.6%, 58.7%, and 19.9% achieving EASI 75, EASI 90, and EASI 100, respectively; 60.2% achieving WP-NRS improvement ≥4 among those with baseline WP-NRS ≥4; 37.0% achieving WP-NRS 0/1 among those with baseline WP-NRS >1; and 26.8% simultaneously achieving EASI 90 and WP-NRS 0/1 by Week 32. Clinically meaningful outcomes were also observed at an earlier visit (Week 20). No new safety signals through Week 32 were identified compared to the established safety profile of UPA.

Most patients with an inadequate response to DUPI at Week 16 experienced clinically meaningful improvements in skin clearance and itch at 4 weeks post-switch to UPA, with additional patients achieving these outcomes by 16 weeks post-switch. These findings suggest that switching from DUPI to UPA is an effective treatment strategy for patients who do not meet moderate or optimal treatment targets with DUPI.

Optimized Second-Generation IL-4Rα Inhibition: Structural and Molecular Dynamics Properties of Rademikibart Fab-IL-4Rα Complex

2024-10-31T18:20:02+00:00

Introduction: Global Burden of Disease studies showed atopic dermatitis (AD) and asthma are the top two immune-mediated inflammatory diseases at younger age [1]. Dupilumab was the initial first-generation interleukin-4 receptor alpha (IL-4Rα) inhibitor for treating both type I and type II IL-4Rα-dependent inflammatory disorders. Following recent clinical trials, rademikibart (previously, CBP-201) emerges as an optimized next-generation human monoclonal antibody with higher binding affinity to IL-4Rα compared to dupilumab [2]. It demonstrated better effect in inhibiting STAT6 intracellular signaling in vitro and provided similar potency inhibiting both IL-4 induced TARC release and IL-4 induced B cell activation [2].

Materials & Methods: X-ray crystallography was used to determine the atomic resolution 3D structure of rademikibart fragment antigen binding (Fab) bound to IL-4Rα. This structure was analyzed and compared computationally with the 2.82 Å resolution crystal structure of dupilumab Fab bound to IL-4Rα (Protein Data Bank Code 6WGL). Molecular dynamics studies on rademikibart and dupilumab bound to IL-4Rα examined the stability of the complexes and effects of amino acid mutations on complex formation.

Results: The x-ray crystal structure of rademikibart Fab bound to IL-4Rα was determined at 2.71Å and compared to the complex of dupilumab Fab and IL-4Rα. The rotation angle between dupilumab and rademikibart bound to IL- 4Rα is 59.17°. This rotation enables the epitope of rademikibart, but not dupilumab, on IL-4Rα to overlap more closely with the conserved binding interface utilized by IL-4 and IL-13 cytokines. Molecular dynamics simulations of rademikibart Fab and dupilumab Fab complexed with IL-4Rα showed the third interface loop (residues 148 to 152 in domain 2) of IL-4Rα interacts directly with rademikibart, which is absent in dupilumab/IL- 4Rα complex. This finding is confirmed by analysis of the hydrogen bond interactions at the interface between the antibodies and IL-4Rα, demonstrating superior binding energy for rademikibart. Through single amino acid mutation analysis on rademikibart, we identified residue Y50 on rademikibart as the key residue interacting with IL- 4Rα’s third interface loop.

Conclusion: Our data provide a molecular and structural rationale for the enhanced IL-4Rα inhibition by rademikibart over dupilumab, confirming rademikibart as an optimized second-generation IL-4Rα inhibitor.

Efficacy and Safety of Ruxolitinib Cream by Anatomic Region in Children Aged 2 to 11 Years With Atopic Dermatitis: Results From TRuE-AD3

2024-11-06T21:01:13+00:00

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease. Ruxolitinib (Janus kinase [JAK]1/JAK2 inhibitor) cream has demonstrated efficacy and safety in patients aged ≥2 years with AD. In adolescents (aged ≥12 y) and adults with AD, application of ruxolitinib cream resulted in significant improvements across all anatomic regions vs vehicle. The objective of this analysis was to evaluate the efficacy and safety of ruxolitinib cream by anatomic region in the randomized, double-blind, phase 3 TRuE-AD3 study (NCT04921969). Children aged 2–11 years with AD for ≥3 months and an Investigator’s Global Assessment score of 2/3 were randomized 2:2:1 to apply 0.75% or 1.5% ruxolitinib cream twice daily (BID) or vehicle BID for 8 weeks. Efficacy was evaluated using the Eczema Area and Severity Index (EASI) subscores for head/neck, trunk, upper limbs, and lower limbs. Of 330 patients in TRuE-AD3, the mean (SD) age was 6.5 (2.9) years, and 179 patients (54.2%) were female; the mean (SD) EASI score was 8.6 (5.4). Improvements in EASI score were demonstrated with 0.75% and 1.5% ruxolitinib cream vs vehicle at first observation (Week 2), with statistically significant differences (at 0.05 alpha level and all P values below are nominal) at Week 8 in the head and neck (−0.63 [P=0.0108] and −0.70 [P=0.0011] vs −0.41), trunk (−0.98 [P=0.0310] and −1.18 [P=0.0003] vs −0.70), upper limbs (−1.81 [P<0.0001] and −2.06 [P<0.0001] vs −1.18), and lower limbs (−2.91 [P<0.0001] and −3.23 [P<0.0001] vs −1.43). Improvements in induration/papulation/edema, erythema, excoriation, and lichenification were observed for both strengths of ruxolitinib cream vs vehicle in all regions at Week 2, with statistical significance (at 0.05 alpha level) in nearly all AD signs and regions at Week 8. Ruxolitinib cream was well tolerated in both treatment groups (n=264), with 4.5% of patients experiencing application site reactions, which was similar to the frequency of application site reactions (4.3%) among patients with head/neck involvement (n=161) . In conclusion, ruxolitinib cream demonstrated significant improvements in AD vs vehicle in children with AD across anatomic regions, including on the head/neck, and was well tolerated. (Funding, Incyte Corporation)

Drying of Opzelura® (Ruxolitinib) Cream 1.5%: Implications for Clinical and Real-World Use

2024-11-06T21:38:52+00:00

Association of Ruxolitinib Cream Initiation With Continued Reduction in Use of Other Topical Treatments, Oral Corticosteroids, and Biologics for Atopic Dermatitis

2024-11-07T00:41:49+00:00

The objective of this analysis was to examine the impact of ruxolitinib cream on the use of other treatments for atopic dermatitis (AD). This study used claims data from the Healthcare Integrated Research Database (HIRD^®) to identify new users of ruxolitinib cream from October 1, 2021, to March 31, 2022. The index date was the date of the first claim for ruxolitinib cream. The baseline period was the 6-month period before the index date, and the follow-up period was 12 months after the index date, which was divided into months 1–6 and months 7–12. Use of other topical and systemic therapies for AD were descriptively analyzed. Among 556 ruxolitinib cream users with follow-up data, the mean number of ruxolitinib cream fills in the overall 12-month follow-up period was 2.1 (SD, 1.77; range, 1–12). The mean (SD) patient age was 40.3 (17.32) years. In months 1–6 and 7–12, 39.9% and 37.4% of patients were treated with ruxolitinib cream monotherapy, respectively; 72.5% and 73.9% of patients did not receive a new class of AD treatment during the respective follow-up periods. Topical corticosteroid use in patients was reduced from 53.4% at baseline to 31.3% in months 1–6 and 26.6% in months 7–12. Topical calcineurin inhibitor use decreased from 14.9% at baseline to 5.2% in months 1–6 and 5.0% in months 7–12. Similarly, topical phosphodiesterase 4 inhibitor use decreased from 6.7% at baseline to 3.4% in months 1–6 and 1.6% in months 7–12. The mean cumulative prednisone-equivalent dose was also reduced from 83.9 mg during the baseline period to 58.0 mg for months 1–6 and 47.3 mg for months 7–12. For patients who did not receive AD biologic therapy during the baseline period (n=431), 92.3% in months 1–6 and 91.4% in months 7–12 continued to remain off AD biologic therapy. Among patients who received AD biologics at baseline (n=125), 16.0% did not receive them in months 1–6 and 26.4% did not receive them in months 7–12. In conclusion, following initiation of ruxolitinib cream, there was a continued reduction in use of other topical therapies and oral corticosteroids for AD. Most biologic-naive patients (>90%) avoided biologics in the 12 months following ruxolitinib cream initiation. Approximately 1 in 4 patients who had biologic treatment during baseline did not continue biologic use in months 7–12. This 12-month analysis confirms earlier 6-month findings that indicated treatment with ruxolitinib cream may reduce the use of other topical therapies, oral corticosteroids, and biologics in patients with AD. (Funding, Incyte Corporation)

Half-life-extended Monoclonal Antibody APG777 for Atopic Dermatitis: Design of the Phase 2 APEX Study

2024-11-07T12:39:27+00:00

Introduction: Current treatments for moderate-to-severe atopic dermatitis (AD) include topical and systemic therapies. The latter includes monoclonal antibodies (mAbs) targeting the IL-13 pathway, which is implicated in AD pathophysiology. While currently available mAbs directed against the IL-13 pathway have demonstrated efficacy for AD, they require ongoing injections every 2 or 4 weeks. APG777 is a humanized, anti-IL-13 mAb that binds IL-13 and blocks downstream signaling mediated by the IL-13Rα1/IL-4Rα complex. APG777 contains amino acid modifications designed to extend plasma half-life through increased FcRn-mediated antibody recycling. Interim results from an ongoing phase 1 study in healthy participants suggest a favorable safety and PK/PD profile for APG777, and a half-life of approximately 75 days.

Methods: APEX (NCT06395948) is a 2-part, multicenter, phase 2, randomized, double-blinded, placebo-controlled clinical trial evaluating the efficacy and safety of APG777 in adults with moderate-to-severe AD. Adults (≥18 years of age) are eligible to participate if they have a diagnosis of AD for ≥1 year prior to screening and exhibit moderate-to-severe AD (EASI ≥16, IGA ≥3, BSA ≥10%) at both screening and baseline visits. Part A of the study (proof-of-concept) is evaluating the efficacy and safety of one induction dose regimen of APG777 compared with placebo over 16 weeks; this is followed by a 36-week maintenance period. Part B (dose-regimen finding) will evaluate different dose regimens of APG777 compared with placebo over 16 weeks followed by a 36-week maintenance period. Participants completing the maintenance period of Part A or B of the study will be eligible to enroll in a separate long-term extension study or enter the post-treatment follow-up period (up to 52 weeks). The primary outcome measure for the study is the percentage change from baseline to week 16 in the Eczema Area and Severity Index (EASI). The APEX study is currently enrolling.

Dupilumab Demonstrates a Higher Likelihood of Achieving Improvements in Signs, Symptoms, and Quality of Life vs. Tralokinumab at Week 16: Results from a Bucher Indirect Treatment Comparison

2024-11-08T06:19:18+00:00

Background: Dupilumab and tralokinumab are biologics approved by the US Food and Drug Administration (FDA) for the treatment of patients with moderate-to-severe atopic dermatitis (AD), aged ≥6 months and ≥12 years, respectively. Dupilumab and tralokinumab have demonstrated efficacy and safety in clinical trials. However, no direct head-to-head trials have been performed to compare the efficacy of dupilumab vs tralokinumab. The Bucher indirect treatment comparison (ITC) is a robust, placebo-adjusted, and accepted method to evaluate the relative efficacy of drugs in the absence of direct comparisons. The objective of this analysis was to report results from a Bucher ITC comparing the efficacy of dupilumab+topical corticosteroid (TCS) vs tralokinumab+TCS at Week 16.

Methods: The placebo-adjusted Bucher ITC included published data from the two similarly designed phase 3 trials, LIBERTY AD CHRONOS (NCT02260986) and ECZTRA 3 (NCT03363854). For both studies, data from the 16-week period were used, employing non-responder imputation, with the following doses: 300mg dupilumab every 2 weeks (q2w)+TCS or placebo+TCS, and 300mg tralokinumab q2w+TCS or placebo+TCS. The evaluated endpoints included the proportions of patients achieving an Investigator’s Global Assessment score 0/1 (IGA 0/1; clear/almost clear), 75% and 90% improvements from baseline in Eczema Area and Severity Index (EASI-75 and EASI-90), ≥4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale score (PP-NRS >4), and ≥4-point improvement from baseline in the Dermatology Life Quality Index (DLQI >4). The Bucher ITC with the frequentist approach was performed using R software (v 4.20; netmeta package) with a fixed-effect model. Results were reported as odds ratio (OR) with 95% confidence interval (CI).

Results: A total of 801 patients (LIBERTY AD CHRONOS: placebo+TCS: 315; dupilumab+TCS: 106; ECZTRA 3: placebo+TCS: 127; tralokinumab+TCS: 253) were included in the Bucher ITC. Baseline disease characteristics indicated comparable severity between the two trial populations based on IGA and PP-NRS. However, CHRONOS showed slightly higher baseline EASI scores (median [Q1, Q3] score 30.9 [22.3, 41.6] vs. ECZTRA 3: 24.7 [18.4, 35.9]), while ECZTRA 3 showed slightly higher DLQI scores (median [Q1, Q3] score 18.0 [12.0, 23.0] vs. CHRONOS: 13.5 [8.0, 20.0]). Patients treated with dupilumab+TCS had a significantly higher likelihood of achieving IGA 0/1 (OR=2.49, 95%CI 1.24–5.00), EASI-75 (OR=3.21, 95%CI 1.66–6.19), EASI-90 (OR=2.92, 95%CI 1.41–6.02), PP-NRS ≥4 (OR=3.62, 95%CI 1.87–7.00), and DLQI ≥4 (OR=2.16, 95%CI 1.03–4.54) at Week 16 vs those treated with tralokinumab+TCS.

Conclusions: A placebo-adjusted Bucher ITC showed that the likelihood of achieving improvements in signs, symptom, and quality of life is significantly higher for patients treated with dupilumab+TCS vs tralokinumab+TCS at Week 16.

Patient and Parent/Caregiver Satisfaction with Efficacy and Cosmetic Elegance of Tapinarof Cream 1% Once Daily in a Long-term Extension Trial in Adults and Children Down to Age 2 Years with Atopic Dermatitis

2024-11-08T18:04:07+00:00

Introduction: Patients with atopic dermatitis (AD) report low satisfaction with currently available topical therapies. Satisfaction and patient preference are closely linked to treatment adherence, and understanding preferences may contribute to improving the quality of AD care and adherence. In the pivotal 8-week, phase 3 ADORING 1 and 2 trials, tapinarof cream 1% (VTAMA^®, Dermavant Sciences, Inc.) once daily (QD) demonstrated superior efficacy versus vehicle and was well tolerated in adults and children down to age 2 years with AD. We report Patient Satisfaction Questionnaire^©(PSQ) results from ADORING 3, a 48-week, open-label extension trial.

Methods: In ADORING 3, eligible patients from ADORING 1 and 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild AD, or moderate or severe AD, that did not meet inclusion criteria for ADORING 1 or 2, were followed for up to 48 weeks. The PSQ was completed at Week 48 or at early termination visit and assessed patient or parent/caregiver satisfaction with tapinarof efficacy, cosmetic elegance (look and feel of tapinarof cream), application ease, impact on daily life, and preference for tapinarof versus prior AD therapies. Patients aged ≥16 years self-completed the PSQ; parents/caregivers completed for children aged 2 to 15 years.

Results: 505 patients or parents/caregivers completed the questionnaire. Respondents consistently reported high rates of satisfaction across all parameters. Most patients or parents/caregivers strongly agreed or agreed with PSQ questions assessing satisfaction with cosmetic elegance (91.5%), quick absorption (89.5%), application ease (97.6%), impact on daily life (94.3%), efficacy (92.3%), and confidence in tapinarof (92.7%). For patients or parents/caregivers who reported prior use of other topical therapies to treat AD, most strongly agreed or agreed that tapinarof was more effective (86.3%), easier to use (68.6%), and that they preferred tapinarof to prior topicals (88.0%). Compared with systemic drugs used previously for AD, most strongly agreed or agreed that tapinarof was more effective (84.6%), easier to use (77.6%), and that they preferred tapinarof to prior systemic drugs (85.9%).

Conclusion: Patient or parent/caregiver satisfaction data from ADORING 3 showed a consistent and highly positive perception of long-term use of tapinarof cream across all parameters, including satisfaction with tapinarof efficacy, cosmetic elegance, application ease, impact on daily life, and preference for tapinarof compared with prior AD therapies. Satisfaction with tapinarof is likely to contribute to long-term adherence and improved outcomes for patients with AD.

Achievement of No-to-minimal Itch and Sleep Improvement with Tapinarof Cream 1% Once Daily in Two Pivotal Phase 3 Trials in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

2024-11-08T18:17:17+00:00

Introduction: Itch frequently causes sleep disturbance in patients with atopic dermatitis (AD). The gold-standard Peak Pruritus Numerical Rating Scale (PP-NRS) improvement from baseline is 4 points; however, more stringent outcomes include achieving no-to-minimal itch (PP-NRS ≤1). Tapinarof cream 1% once daily (QD) demonstrated superior efficacy, including itch reduction, versus vehicle and was well tolerated in adults and children down to 2 years of age with AD in the ADORING 1 and 2 pivotal phase 3 trials. Here we present highly stringent itch outcomes and sleep improvement with tapinarof from these trials.

Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic Dermatitis™ score ≥3 (moderate or severe), Eczema Area and Severity Index score ≥6, and body surface area involvement of 5–35% were randomized to tapinarof cream or vehicle QD for 8 weeks. Stringent
PP-NRS assessments were analyzed post hoc and included achieving no‑to‑minimal itch (PP-NRS ≤1) or PP-NRS score <2. Mean weekly PP-NRS scores were assessed on an 11-point scale (0 indicates “no itch” and 10 is “worst imaginable itch”). The Patient Oriented Eczema Measure (POEM) question 2 evaluated sleep disturbance on a 5-point scale (0 indicates “no days” and 4 is “every day”); outcomes were pooled and stratified by age.

Results: 407 and 406 patients were randomized in ADORING 1 and 2. Mean baseline scores were similar across ADORING 1 and 2 treatment groups: PP-NRS, 6.7 and 6.8; pooled POEM sleep disturbance scores, 2.0 (aged ≥12 years) and 2.4 (<12 years), respectively. Statistically significant achievement of no-to-minimal itch (PP-NRS ≤1), PP-NRS <2, and improvement in sleep were achieved with tapinarof versus vehicle as early as Week 1, the first assessment, and continued through Week 8. Stringent itch outcomes were achieved with tapinarof versus vehicle at Week 8: no-to-minimal itch, 31.4% versus 17.4% (P=0.0072) and 33.0% versus 14.0% (P=0.0003); and PP-NRS <2, 48.1% versus 28.4% (P=0.0006) and 46.8% versus 19.6% (P<0.0001) in ADORING 1 and 2, respectively. Sleep scores improved with tapinarof versus vehicle at Week 8: –1.4 versus –0.8 (≥12 years); –1.7 versus –1.0 (<12 years; both P<0.0001).

Conclusion: Tapinarof cream 1% QD demonstrated early, significant, and meaningful achievement of no-to-minimal itch and improvement of sleep in adults and children down to 2 years of age with AD.

Skin Clearance, Treatment Response Off-therapy, and Safety of Tapinarof Cream 1% Once Daily: Results from ADORING 3, a 48-week Phase 3 Trial in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

2024-11-08T18:29:52+00:00

Introduction: In the ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA^®, Dermavant Sciences, Inc.) once daily (QD) demonstrated significant efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability outcomes from ADORING 3.

Methods: Eligible patients from ADORING 1, ADORING 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild, or moderate or severe AD, that did not meet eligibility criteria for ADORING 1 or 2, received tapinarof cream 1% QD for up to 48 weeks. Efficacy endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™] score=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Safety and tolerability were assessed. Patients entering with vIGA-AD™≥1 were treated with tapinarof until complete clearance (vIGA-AD™=0 [clear]). Those entering with or achieving complete clearance discontinued tapinarof and were assessed for maintenance of clear or almost clear skin off-treatment (duration of treatment-free interval). Patients whose AD returned to mild (vIGA-AD™≥2) were re-treated until complete clearance was achieved.

Results: 728 patients enrolled; 83.0% were pediatric (2–17 years). Overall, 51.9% (378/728) achieved complete disease clearance, and 81.6% achieved clear or almost clear skin at least once in the trial. Mean duration of first treatment-free interval was 79.8 consecutive days (standard deviation: 81.4 days). No tachyphylaxis on either continuous or intermittent therapy was observed for up to 48 weeks. Most frequent adverse events were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Follicular events and contact dermatitis were mostly mild or moderate and associated with low discontinuations (1.0% and 0.4%, respectively). Tapinarof was well tolerated locally, even when applied on sensitive skin.

Conclusions: Tapinarof cream monotherapy demonstrated a high rate of complete disease clearance in patients down to age 2 years with AD. After discontinuing tapinarof, patients maintained clear or almost clear skin for 79.8 consecutive days. Tapinarof was well tolerated over 48 weeks.

Why Do Optimal Targets for Itch and Skin Clearance Matter in Atopic Dermatitis Treatment? Insights from TARGET-DERM AD Registry

2024-11-13T18:47:30+00:00

Introduction/Background: Atopic dermatitis (AD) patients undergoing treatment may only experience partial improvement in itch and skin lesions, often leading to suboptimal outcomes. The Aiming High in Eczema/Atopic Dermatitis (AHEAD) treat-to-target recommendations emphasize the importance of achieving optimal treatment targets, such as complete or near-complete itch relief and skin clearance. However, there is limited evidence on the impact of achieving these higher efficacy targets on patient-reported outcomes and quality of life in AD.

Objectives: To evaluate the independent and combined effects of achieving optimal treatment targets for itch and skin clearance on patient-reported outcomes (PROs) in AD, based on the AHEAD treat-to-target recommendations.

Method: A cross-sectional analysis was conducted on adult participants in TARGET-DERM AD, a longitudinal study with over 4,000 participants across 52 U.S. and Canadian clinical-practice sites (2019-2024). Itch severity was measured using the PROMIS Itch-Severity question (NRS-Itch, 0–10 scale), with scores of 0/1 indicating no or minimal itch. Skin severity was assessed using the validated Investigator Global Assessment (vIGA-AD), where 0/1 represents clear or almost clear skin. Associations between itch and skin severity with optimal patient outcomes including POEM 0–2 (clear/almost-clear disease), DLQI 0/1 (minimal/no impact on quality of life), NRS-Sleep 0/1, and NRS-Pain 0/1 were evaluated. Logistic regression models examined the main and interaction effects of itch and skin severity.

Results: Among 1,920 patients (58.6% female; 54.5% Non-Hispanic White; 93.8% US; mean age 45 years), optimal DLQI, POEM, NRS-Sleep, and NRS-Pain occurred most frequently among those achieving the optimal treatment targets for itch (WI-NRS 0/1; 52.1%, 53.7%, 57.3%, and 83.1%, respectively) and skin clearance (vIGA-AD 0/1; 44.7%, 44.3%, 44.7%, and 74.3%, respectively). Compared to partial improvement, the adjusted odds ratios (aOR) of optimal PROs were greatest for participants with complete or near-complete resolution of both itch and skin lesions (DLQI 0/1: 20.0; POEM 0-2: 41.7; Sleep-NRS: 16.1; Pain-NRS: 6.0).

Conclusions: Achieving optimal treatment targets for both itch and skin lesions markedly enhances patient-reported outcomes in AD. The results of this real-world study support treat-to-optimal targets to assess therapeutic effectiveness and optimize patient outcomes.

Persistent Inadequate Disease Control and Therapeutic Inertia in Moderate-to-Severe Atopic Dermatitis: A 12-month Longitudinal Analysis of Real-world Outcomes from the TARGET-DERM AD registry

2024-11-13T20:30:23+00:00

Background: Therapeutic inertia refers to the delay or failure in treatment escalation in patients not achieving adequate disease control; it is a challenge in the management of moderate-to-severe atopic dermatitis (AD). Despite the availability of conventional (CST) and advanced systemic therapies (AST) utilized for the treatment of moderate to severe AD, many patients do not achieve treatment success. However, the extent of this inadequacy in real-world clinical practice remains underexplored.

Objectives: This study evaluates the occurrence of therapeutic inertia and the proportion of patients with moderate-to-severe AD who continue to show inadequate response after receiving systemic therapies for a duration from 3 to 12 months

Methods: We conducted a longitudinal analysis of patients with moderate-to-severe AD (vIGA-AD≥3) from the TARGET-DERM AD registry, including 3,457 participants from 39 centers in the U.S. and Canada. Eligible patients had documented outcomes at the initiation of systemic therapy and after 3 months up to 12 months of follow up. We assessed clinician- and patient-reported outcomes to identify the proportion of patients not meeting treatment targets based on expert consensus. An inadequate response was defined as not achieving a validated Investigator Global Assessment (vIGA-AD) score ≤2, a 50% improvement in Body Surface Area (BSA), and a ≥4-point reduction in the Worst Pruritus Numeric Rating Scale (WP-NRS). An optimal response was defined as a vIGA-AD score ≤1 (clear or almost clear skin), BSA ≤2%, and WP-NRS itch score of 0/1 (complete or almost complete skin resolution).

Results: Out of 2,107 patients with moderate-to-severe AD, 445 met the inclusion criteria. The majority were adults (63.8%), female (62.0%), and Non-Hispanic White (45.4%), with an average age of 31 years. Most patients (88.8%) initiated treatment with AST, with dupilumab being the most common (86.5%). The mean vIGA-AD was 3.3 for AST and 3.6 for CST at initiation (P<0.01). At 6 months, 37% and 67% of AST-treated patients had inadequate responses in terms of skin clearance and itch outcomes, respectively, while 82% and 79% did not achieve optimal responses. At 12 months, these figures were approximately 30% and 66% for inadequate responses and 85% and 88% for not achieving optimal responses, respectively. CST-treated patients showed a similar trend.

Conclusions: The study reveals that a significant portion of moderate-to-severe AD patients fail to achieve adequate disease control with systemic therapies over 12 months, indicating substantial presence of therapeutic inertia. These findings suggest a need for more proactive management strategies in AD treatment.

Impact of Therapeutic Inertia on Patient-Reported Outcomes in Moderate-to-Severe Atopic Dermatitis: A 12-Month Longitudinal Study from the TARGET-DERM AD Registry

2024-11-13T20:45:10+00:00

Background: Therapeutic inertia, the delay or reluctance to modify treatment when goals are unmet, is a significant challenge in managing chronic diseases, including atopic dermatitis (AD). This inertia can lead to suboptimal disease control and affect patient outcomes.

Objectives: This study evaluates the effect of therapeutic inertia on patient-reported outcomes (PROs) in moderate-to-severe AD patients undergoing systemic treatment over 3 to 12 months.

Methods: We analyzed longitudinal data from the TARGET-DERM AD registry, which includes 3,457 patients with moderate-to-severe AD from 39 centers across the U.S. and Canada. Eligible patients had documented patient-reported outcomes (PROs) at the initiation of systemic therapy and at subsequent 3-month intervals up to 12 months of follow-up. We assessed the proportion of patients not meeting treatment targets based on expert consensus. Patients had a validated Investigator Global Assessment (vIGA-AD) score of 3 or more at initiation of either an advanced systemic therapy (AST) such as biologics or JAK inhibitors or a conventional systemic therapy (CST) such as cyclosporine, methotrexate, or prednisone. PROs were evaluated at 3-month intervals up to 12 months, assessing achievement against the predefined treatment targets. PRO measures included Worst-Itch (PROMIS Itch-Severity), POEM, PO-SCORAD, NRS-sleep, and NRS-pain with specific moderate and optimal target levels established for each. Itch-Severity (range: 0–10; moderate target: ≥4-point reduction, optimal target: score ≤1), POEM (range: 0-28; moderate target: ≥4-point reduction, optimal target: score ≤2), PO-SCORAD (range: 0-103; moderate target: score ≤24; optimal target: score ≤10), NRS-sleep and NRS-pain (range: 0-10; moderate target: reduction ≥3-points; optimal target: score ≤1).

Results: Out of 2107 patients with moderate-to-severe AD, 445 qualifying participants were included (63.8% adult, 62.0% female, 45.4% Non-Hispanic White, mean age of 31 years). Most patients (88.8%) initiated AST, with dupilumab being the most common (86.5%). At 6 months, significant proportions of AST-treated patients failed to reach moderate and optimal targets for itch (67% and 79%, respectively), POEM (46% and 69%), and NRS-sleep (59% and 47%). By 12 months, these figures were similar, with 66% and 88% failing to meet itch targets, 53% and 73% failing to meet POEM targets, and 62% and 45% failing to meet NRS-sleep targets, respectively. A similar pattern was observed for other PROs. CST-treated patients exhibited similar trends.

Conclusions: The study highlights the profound impact of therapeutic inertia on the quality of life of patients with moderate-to-severe AD. Despite systemic therapy, a considerable proportion failed to meet treatment targets over a 12-month period, underscoring the need for more proactive and responsive treatment strategies in AD management.

Maintenance of Response to Risankizumab in Patients With Psoriatic Arthritis: A 4-Year Analysis of the KEEPsAKE 1 and 2 Trials

2024-11-01T18:14:06+00:00

Introduction: Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, specifically inhibits the p19 subunit of human interleukin 23 and is approved for treatment of active psoriatic arthritis (PsA) in adults. This post hoc analysis evaluated the long-term maintenance of clinical response through ~4 years of risankizumab treatment using data from 2 ongoing phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2.

Methods: Eligible patients had active PsA with inadequate response or intolerance to ≥1 conventional synthetic disease modifying antirheumatic drugs (KEEPsAKE 1 [NCT03675308]; KEEPsAKE 2 [NCT03671148]) and/or inadequate response or intolerance to 1–2 biologic therapies (KEEPsAKE 2 only). Patients received double-blinded risankizumab 150 mg or placebo for 24 weeks and open-label risankizumab 150 mg thereafter. This analysis includes patients who received continuous risankizumab through both treatment periods. Assessments included improvement of ≥20%/50%/70% in PsA symptoms using American College of Rheumatology criteria (ACR20/50/70), achievement of minimal disease activity (MDA), reduction of ≥90% in Psoriasis Area and Severity Index (PASI 90; in patients with ≥3% body surface area affected by psoriasis at baseline), and clinically meaningful reduction in pain (≥10 mm on a visual analog scale [VAS]). All data were reported as observed.

Results: Among patients who achieved ACR20 at week 24 in KEEPsAKE 1 or KEEPsAKE 2, 70.7% and 86.4% maintained ACR20 responses at week 196. Similarly, ACR20 response was maintained to week 196 by 85.7% and 83.3% of week 52 responders in KEEPsAKE 1 and 2, respectively. Similar patterns of maintenance of response were observed for ACR50 and ACR70. Most patients also maintained MDA at week 196 from weeks 24 and 52 (Week 24: KEEPsAKE 1, 86.0%; KEEPsAKE 2, 81.3%; Week 52: KEEPsAKE 1, 81.2%; KEEPsAKE 2, 85.5%). The PASI 90 response was maintained at week 196 from weeks 24 and 52 (Week 24: KEEPsAKE 1, 88.2%; KEEPsAKE 2, 94.9%; Week 52: KEEPsAKE 1, 92.6%; KEEPsAKE 2, 97.1%). Weeks 24 and 52 responders maintained clinically meaningful reductions in pain VAS at week 196 (Week 24: KEEPsAKE 1, 90.2%; KEEPsAKE 2, 88.9%; Week 52: KEEPsAKE 1, 88.3%; KEEPsAKE 2, 90.1%), respectively.

Conclusion: Risankizumab demonstrated durable long-term efficacy in patients with active PsA. A high proportion of patients receiving continuous risankizumab treatment in KEEPsAKE 1 and KEEPsAKE 2 maintained ACR20/50/70, MDA, or PASI90 responses and meaningful pain reduction through week 196.

Long-Term Efficacy and Safety of Risankizumab for csDMARD-IR Patients With Active Psoriatic Arthritis: 196-Week Results From the KEEPsAKE 1 Trial

2024-11-07T16:51:21+00:00

Introduction & Objectives: Here, we report the long-term efficacy and safety of risankizumab (RZB) in patients with active psoriatic arthritis (PsA) through week 196 from the KEEPsAKE 1 trial.

Materials & Methods: The ongoing KEEPsAKE 1 clinical trial is a global, phase 3, multicenter study to evaluate the efficacy and safety of RZB versus placebo (PBO) in patients with active PsA. Patients are at least 18 years old and demonstrated an inadequate response, intolerance or contraindication to ≥1 conventional synthetic disease modifying antirheumatic drug (csDMARD-IR). Following a 24-week double-blind, PBO-controlled, parallel-group treatment period (period 1), all patients received open-label RZB every 12 weeks thereafter (period 2). Safety assessments were based on monitoring of treatment-emergent adverse events (TEAEs) reported as events per 100 patient-years (PY). Efficacy and safety analyses were conducted in all randomized patients who received ≥1 dose of the study drug.

Results: Overall efficacy results were maintained at week 196 of the KEEPsAKE 1 trial, as compared to previously reported timepoints. At week 196, 39.4% of patients receiving continuous RZB and 38.1% of PBO/RZB patients achieved ACR50; 39.6% of RZB and 35.2% of PBO/RZB patients achieved MDA. In patients with psoriasis severity of ≥ 3% of body surface area (BSA) at baseline, 65.2% on RZB and 62.9% on PBO/RZB achieved PASI90 at week 196. mNAPSI and PGA-F scores improved from baseline by 14.99 and 1.5 points, respectively, for RZB, and by 14.73 and 1.5 points for PBO/RZB patients. In patients with enthesitis at baseline, 60.1% on RZB and 63.4% on PBO/RZB achieved resolution. For patients with dactylitis at baseline, 72.3% on RZB and 77.6% on PBO/RZB achieved resolution. HAQ-DI (RZB -0.40, PBO/RZB -0.33), SF-36 PCS (RZB 8.98, PBO/RZB 7.21) and FACIT-Fatigue (RZB 7.7, PBO/RZB 5.6) scores maintained improvement from baseline to week 196. The overall rates of TEAEs (121.4 E/100PY), serious TEAEs (7.7 E/100PY) and AEs leading to discontinuation of study drug (1.8 E/100PY) have remained stable and comparable to those reported in period 1.

Conclusion: The 196-week results of the ongoing KEEPsAKE 1 trial demonstrate the durable efficacy of RZB 150 mg in treating the different clinical manifestations and improving health-related quality of life in csDMARD-IR patients with PsA. RZB continued to be well-tolerated, with no new safety signals.

Long-Term Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 196-Week Results From the KEEPsAKE 2 Trial

2024-11-07T17:19:02+00:00

Introduction & Objectives: Here, we report the long-term efficacy and safety of risankizumab (RZB) in patients with active psoriatic arthritis (PsA) through week 196 of the KEEPsAKE 2 trial.

Materials & Methods: Adult patients with previous inadequate response or intolerance to 1 or 2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) were randomized in a 1:1 ratio to subcutaneous RZB 150mg or matched placebo for a 24-week double-blind placebo controlled period. Starting at week 28, patients received open-label RZB every 12 weeks thereafter. Efficacy and safety analyses were conducted in all randomized patients who received ≥1 dose of the study drug. Statistical approaches included non-responder imputation incorporating multiple imputation (NRI-MI) for binary endpoints, and mixed-effect model for repeated measures (MMRM) for categorical endpoints at week 196. Safety assessments based on treatment emergent adverse events (TEAEs) are summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [E/100PYs]).

Results: 51.3% of patients on RZB 150mg (N=224) achieved the primary endpoint of ACR20 at week 24 compared to 26.5% on placebo (N=219). Patients on open-label RZB maintained similar efficacy results at week 196 as those reported previously at weeks 24, 52, 100, and 148. At week 196, 54.5% patients receiving continuous RZB and 50.2% patients on PBO/RZB achieved ACR20; 35.3% on RZB and 37.0% on PBO/RZB achieved ACR50; 35.3% on RZB and 37.4% on PBO/RZB achieved minimal disease activity (MDA). In patients with psoriasis severity of ≥ 3% of body surface area (BSA) at baseline, 66.7% on RZB and 56.3% on PBO/RZB achieved PASI90 at week 196. In patients with enthesitis at baseline, 49.0% on RZB and 50.0% on PBO/RZB achieved resolution. In patients with dactylitis at baseline, 75.0% on RZB and 59.6% on PBO/RZB achieved resolution. Among patients with HAQ-DI scores of at least 0.35 at baseline, 36.7% on RZB and 40.6% on PBO/RZB achieved improvements of at least 0.35 at week 196. The overall rates of TEAEs (170.7 E/100PYs), serious TEAEs (9.8 E/100PYs) and AEs leading to discontinuation of study drug (1.4 E/100PYs) remained stable and consistent with rates reported previously at week 24 for the placebo-controlled period, and weeks 52, 100, and 148.

Conclusion: The 196-week results from KEEPsAKE 2 demonstrate that long-term treatment with RZB shows durable efficacy in Bio-IR and/or csDMARD-IR patients with PsA, with no new safety findings.

Retrospective Analysis of the Impact of Screening for Psoriatic Arthritis (PsA) with the Psoriasis Epidemiology Screening Tool (PEST) in Clinical Dermatology Practice

2024-11-08T19:26:44+00:00

Introduction: Patients with plaque psoriasis (PSO) have an increased risk of developing PsA as the disease severity progresses. While it is estimated that 30% of patients with PSO have PsA, nearly 16% of patients with PSO may have undiagnosed PsA.^1,2Implementing the PEST questionnaire for PsA screening in dermatologic practice may increase early intervention by improving rates of timely diagnosis.³ This observational study aimed to assess the proportion of patients with PSO and no previous PsA diagnosis who screened positive on the PEST and were then diagnosed with PsA by a healthcare provider in the PEST deployment period within the Advanced Dermatology and Cosmetic Surgery (ADCS) specialty dermatology network.

Procedure/Study: De-identified, real-world patient data [2018–2019 and 2021–2022] were sourced from electronic health records within the ADCS network of outpatient facilities across 14 states in the United States. Patients were included in the analysis if they received care at an ADCS facility where the PEST was deployed, had ≥1 encounter with a diagnosis code for PSO, and never had a diagnosis code for PsA before their first diagnosis code for PSO. For outcomes directly related to PEST evaluations, data from 1/1/2021–12/31/2022 (PEST deployment period) were used. For outcomes not directly related to PEST results, data from 1/1/2018–12/31/2019 (period before PEST deployment) were evaluated. Descriptive statistics, including frequencies, percentages, and 95% confidence intervals (CIs) for categorical variables, were used to characterize the patient cohorts by study period.

Results: Among ADCS facilities using the PEST during the deployment period (44% of practices in the network), the final study population included 14,308 and 21,142 patients with PSO in the period before PEST deployment and during the PEST deployment period, respectively. In the PEST deployment cohort, 1,100 (5.2%; 95% CI: 4.9–5.5) patients were screened using the PEST. In the period before PEST deployment, 327 (2.3%; 95% CI: 2.0–2.5) patients with PSO and no previous PsA diagnosis were subsequently diagnosed with PsA. During the PEST deployment period, 449 (2.1%; 95% CI: 1.9–2.3) patients with PSO and no previous PsA diagnosis received a subsequent PsA diagnosis without PEST screening. Of all patients with PSO who screened positive for PsA on the PEST (score ≥3; n=296), 10.8% (n=32; 95% CI: 7.6–15.1) subsequently received a formal PsA diagnosis during the PEST deployment period.

Conclusion: These results suggest that a meaningful proportion of patients with PsA may be underdiagnosed in the dermatology setting. Deployment of the PEST in the clinical dermatologic workflow may provide an opportunity to diagnose PsA earlier and improve patient outcomes.

Bimekizumab Efficacy and Safety Through 2 years in Patients with Hidradenitis Suppurativa: Results from the Phase 3 BE HEARD I&II trials and Open-Label Extension BE HEARD EXT

2024-11-07T15:32:44+00:00

Introduction: Interleukin (IL)-17F and IL-17A play a role in the immunopathogenesis of hidradenitis suppurativa (HS).^1–3 Bimekizumab (BKZ) is a humanized IgG1 monoclonal antibody that selectively inhibits IL-17F in addition to IL-17A leading to clinically meaningful improvements in patients (pts) with HS.^4,5 Here, BKZ efficacy and safety data (OC) are presented over 2 years (96 weeks [wks]) for the pooled BE HEARD I&II (BHI&II) trials and BE HEARD EXT (BHEXT).^5,6

Procedure/Study: In BHI&II, pts with moderate to severe HS were randomized 2:2:2:1 (16wk-initial/32wk-maintenance) to BKZ 320mg every 2 wks (Q2W)/Q2W, BKZQ2W/Q4W, BKZQ4W/Q4W or placebo/BKZQ2W.⁵ Wk48 completers could enroll in BHEXT and receive open-label BKZQ2W or BKZQ4W based on ≥90% HS Clinical Response (HiSCR90; averaged from Wks36/40/44). We report HiSCR50/75/90/100 rates, percentage change from baseline (%CfB, mean±SD) in International HS Severity Score System (IHS4) and draining tunnel (DT) count, and Dermatology Life Quality Index (DLQI) 0/1 achievement at Wks48/96 for patients randomized to BKZ in BHI&II and entered BHEXT (BKZ Total, observed case). Safety outcomes reported for pts who received ≥1 BKZ dose across BHI&II/BHEXT.

Results: 556 pts randomized at baseline to BKZ in BHI&II completed Wk48 and entered BHEXT; 446 pts completed Wk96. At Wk48, HiSCR50/75/90/100 was achieved by 79.9/64.0/42.3/30.2% of pts; responses improved to Wk96: 85.4/77.1/57.6/44.2%. Baseline IHS4 was 35.6±31.5; %CfB at Wk48/96 was
–70.3±39.6/−79.8±28.1%. Baseline DTs were 3.8±4.3; the %CfB at Wk48/96 was −57.5±72.9%/−73.7±45.7%. Baseline DLQI was 11.0±6.8; 27.4% (151/551) of pts achieved DLQI 0/1 at Wk48 and 33.9% (149/439) at Wk96. Over 2 years, 917/995 (248.9/100 pt years [PY]) pts experienced a treatment-emergent adverse event (TEAE). Serious TEAEs were reported in 122 (7.2/100 PY) pts; 109 (6.3/100 PY) pts discontinued due to a TEAE. Serious infections occurred in 33 (1.9/100 PY) pts. Safety data were comparable with BHI&II.⁵

Conclusion: In pts treated with BKZ, clinically meaningful improvements in efficacy outcomes observed at 1 year, including the HiSCR 75/90/100, IHS4, and DT count endpoints, were maintained to 2 years; improvements in quality of life were maintained. No new safety signals were observed; the safety profile over 2 years was consistent with BHI&II and BKZ studies in other indications.^5,7–9

Bimekizumab Effect on the Need for Concomitant Rescue Interventions by HiSCR Response Level in Patients with Moderate to Severe Hidradenitis Suppurativa from BE HEARD I&II

2024-11-07T15:33:31+00:00

Introduction: Hidradenitis suppurativa (HS) is a chronic, systemic, inflammatory skin disease characterized by deep, painful lesions that negatively impact patients’ (pts’) quality of life.¹ These lesions are difficult to treat and require multifaceted treatment, including the need for rescue interventions alongside conventional therapy.¹ Bimekizumab (BKZ) is a monoclonal IgG1 antibody that inhibits interleukin (IL)-17F in addition to IL-17A.² Here, the relationship between increasingly stringent HS Clinical Response (HiSCR) levels achieved with BKZ and the proportion of pts not requiring rescue concomitant interventions is investigated.
Procedure/Study: Pooled data are presented from the phase 3 BE HEARD I&II trials maintenance treatment period (Weeks [Wks]16–48).³ Pts were randomized 2:2:2:1 (initial/maintenance treatment period) to BKZ 320 mg every 2 wks (Q2W)/Q2W, BKZ Q2W/Q4W, BKZ Q4W/Q4W, or placebo (PBO)/BKZ Q2W. Data for the individual BKZ randomization arms and pooled across these arms (BKZ Total) are reported. BKZ-randomized pts were grouped by achievement of mutually exclusive HiSCR levels (<50% improvement from baseline [<HiSCR50]; HiSCR50–<75; HiSCR75–100) at Wk16. The incidence of pts not requiring any concomitant rescue interventions during the maintenance treatment period, including medical (antibiotics, analgesics) and procedural (incision/drainage, intralesional triamcinolone injection) interventions, are reported. Data reported as observed case.

Results: Overall, 868 pts were randomized to BKZ Q2W/Q2W (N=288), BKZ Q2W/Q4W (N=292), or BKZ Q4W/Q4W (N=288). In BKZ Total, 76.0%/83.2%/89.1% of pts in the HiSCR<50/50–<75/75–100 bands did not receive rescue intervention through Wks16–48, demonstrating a numerical increase with increasing HiSCR bands. Comparable trends across HiSCR<50/50–<75/75–100 bands were observed in pts receiving BKZ Q2W/Q2W (79.8%/90.0%/90.9%), BKZ Q2W/Q4W (75.0%/78.3%/89.0%) or BKZ Q4W/Q4W (73.3%/81.4%/87.1%). Similar trends were observed from the lowest to highest HiSCR bands when separating into any medical or procedural interventions.

Conclusion: Overall, the majority of BKZ-randomized pts did not require any concomitant rescue medical or procedural interventions through Wks16–48 and the proportions of these pts increased with increasingly stringent HiSCR bands. These data highlight the additional value to pts of a decreased need for concomitant rescue interventions when they achieve higher HiSCR response levels.

References: 1. Zouboulis CC. J Eur Acad Dermatol Venereol 2015;29:619–44; 2. Adams R. Front Immunol 2020;11:1894; 3. Kimball AB. Lancet 2024;403:2504–19.

Bimekizumab impact on draining tunnels: A dynamic assessment in patients with moderate to severe HS using pooled Week 48 results from BE HEARD I&II

2024-11-07T15:34:20+00:00

Introduction: Hidradenitis suppurativa (HS) is a recurrent, inflammatory skin disease characterized by painful skin lesions in the folds of the skin and deep, dermal abscesses that join to form chronically draining tunnels (DTs).^1,2 Bimekizumab (BKZ) is a humanized IgG1 monoclonal antibody that selectively inhibits IL-17F in addition to IL-17A, both abundant in lesional skin.^3,4 Here, we assess the effect of BKZ on DT outcomes over 48 weeks (wks) in BE HEARD I&II.⁵
Procedure/Study: Pooled data included an initial (Wks0–16) and maintenance (Wks16–48) treatment period. Randomization: 2:2:2:1 (initial/maintenance) to BKZ 320mg every 2 wks (Q2W)/Q2W, BKZ Q2W/Q4W, BKZ Q4W/Q4W or placebo (PBO)/BKZ Q2W. Proportions of patients with ≥1/≥3 DTs at baseline achieving 0, 1–2, 3–5 or >5 DTs were analyzed to Wk48 (observed case).
Results: Overall, 1,014 patients were randomized to BKZ Q2W/Q2W (N=288), BKZ Q2W/Q4W (N=292), BKZ Q4W/Q4W (N=288) or PBO/BKZ Q2W (N=146). At baseline, in patients with ≥1 DT, proportions with 1–2 DTs ranged from 34.2–37.4%; 3–5 DTs: 27.0–36.9%; >5 DTs: 28.8–35.5%. In patients with ≥3 DTs, proportions with 3–5 DTs ranged from 43.2–56.1%; >5 DTs: 43.9–56.8%.
At Wk16, higher proportions of BKZ-treated patients with ≥1 DT at baseline achieved 0 DTs vs PBO: BKZ Q2W/Q2W, 35.4%; BKZ Q2W/Q4W, 35.4%; BKZ Q4W/Q4W, 33.1% vs PBO, 24.7%. At Wk48, the proportions of patients receiving continuous BKZ that achieved 0 DTs increased to: 45.5%, 48.8%, and 46.8% respectively; PBO/BKZ Q2W switchers showed similar trends (46.3%). For patients with ≥3 DTs at baseline, at Wk16 a higher proportion receiving BKZ achieved 0 DTs vs PBO: BKZ Q2W/Q2W, 24.6%; BKZ Q2W/Q4W, 26.8%; BKZ Q4W/Q4W, 21.7%; vs PBO, 11.5%. At Wk48, the proportions receiving continuous BKZ that achieved 0 DTs increased to 35.0%, 42.2%, and 36.0%, respectively. PBO/BKZ Q2W switchers achieved similar levels (38.0%), with a more favorable increase from Wk16 to Wk48 than PBO/BKZ Q2W switchers with ≥1 DT at baseline.
Conclusion: At Wk16, a higher proportion of BKZ-treated vs PBO patients with ≥1/≥3 DTs at baseline achieved 0 or 1–2 DTs; proportions increased to Wk48 regardless of treatment arm.

Bimekizumab impact on patient-reported outcomes in patients with moderate to severe hidradenitis suppurativa: Pooled Week 48 results from BE HEARD I&II

2024-11-07T15:34:32+00:00

Introduction: Hidradenitis suppurativa (HS) has substantial negative effects on patients’ lives,¹ with debilitating symptoms, such as intense pain/fatigue/draining and odor, which lead to overall low quality of life (QoL).^1,2 Bimekizumab (BKZ) is a humanized IgG1 monoclonal antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A; clinical efficacy was previously shown in the phase 3 BE HEARD I&II trials.³ Here, the impact of BKZ on patient-reported outcomes (PROs) in patients with moderate to severe HS in BE HEARD I&II is reported.

Procedure/Study: Pooled data included an initial (Weeks [Wks]0–16) and maintenance (Wks16–48) treatment period. Patients were randomized 2:2:2:1 (initial/maintenance) to BKZ 320 mg every 2 wks (Q2W)/Q2W, BKZ Q2W/ Q4W, BKZ Q4W/Q4W or placebo (PBO)/BKZ Q2W. HS Symptom Questionnaire (HSSQ; each symptom item scored 0–10) mean values are reported to Wk48 for skin pain, itch, smell/odor, and drainage/oozing. Proportions of patients achieving minimal clinically important difference (MCID) for Dermatology Life Quality Index (DLQI; scored 0–30; improvement from baseline score ≥4) were reported at Wk16 and Wk48. Data are reported as observed case.

Results: Overall, 1,014 patients were randomized to BKZ Q2W/Q2W (N=288), BKZ Q2W/Q4W (N=292), BKZ Q4W/Q4W (N=288), PBO/BKZ Q2W (N=146). Within each HSSQ item, similar baseline scores were observed across treatment groups. At Wk16, for skin pain, itch, smell/odor and draining/oozing, greater improvements (i.e. score reduction) from baseline were seen in BKZ- vs PBO-treated patients. HSSQ item scores were substantially reduced from Wk16 to Wk48 in Wk16 PBO/BKZ switchers, further decreases were observed in those continually treated with BKZ. At Wk16, a greater proportion of BKZ- vs PBO-treated patients achieved MCID in DLQI: BKZ Q2W/Q2W, 64.6%; BKZ Q2W/Q4W, 54.9%; BKZ Q4W/Q4W, 63.5% vs PBO, 49.1%. At Wk48, a greater proportion of patients continually treated with BKZ achieved MCID in DLQI vs at Wk16; Wk16 PBO/BKZ switchers attained similar proportions (BKZ Q2W/Q2W: 73.4%; BKZ Q2W/Q4W: 63.5%; BKZ Q4W/Q4W: 74.5%; PBO/BKZ Q2W: 76.5%).

Conclusion: At Wk16, BKZ-treated patients achieved a reduction from baseline of HS symptoms: skin pain, itch, smell/odor, and drainage/oozing. Clinically meaningful health-related QoL improvements from baseline were observed and maintained/slightly improved through Wk48. PBO/BKZ switchers experienced improvements in PRO responses from Wk16 to Wk48 and achieved comparable outcomes at Wk48 to patients continually treated with BKZ.

Bimekizumab cumulative clinical benefit in patients with moderate to severe hidradenitis suppurativa through 1 year of the BE HEARD I&II phase 3 trials

2024-11-07T15:35:43+00:00

Introduction: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease which significantly impacts health-related quality of life.¹ Bimekizumab (BKZ) is a humanized IgG1 monoclonal antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A.²ere, the cumulative benefit of BKZ treatment on HS clinical response (HiSCR) through 16 and 48 weeks (wks) is reported using area under the curve (AUC) analyses.
Procedure/study: Pooled data from BE HEARD I&II included an initial (Wks0–16) and maintenance treatment period (Wks16–48).³ Randomization: 2:2:2:1 (initial/maintenance) BKZ 320mg every 2 wks (Q2W)/Q2W, BKZ Q2W/Q4W, BKZ Q4W/Q4W, or placebo (PBO)/BKZ Q2W. HiSCR50/75/90 response was achieved at a given visit if there was ≥50/75/90% reduction in the total abscess/inflammatory nodule count with no increase from baseline in abscess or draining tunnel count. Cumulative clinical benefit estimation: total AUC through Wk48 for HiSCR50/75/90 achievers. Calculation of estimated number of days patients achieved each response: proportion of total possible AUC for each outcome multiplied by total number of days in the period (Wks0–16: 112 days, Wks0–48: 336). Data are reported as observed case, where N represents number of patients with a non-missing lesion count assessment in the given week, and percentages are calculated accordingly (i.e. where data recorded after an intercurrent event are included).
Results: Overall, 1,014 patients were randomized to BKZ Q2W/Q2W (N=288), BKZ Q2W/Q4W (N=292), BKZ Q4W/Q4W (N=288) and PBO/BKZ Q2W (N=146). Through 16wks, the total number of days patients achieved HiSCR50 was almost double in BKZ Q2W/Q2W (47 days), BKZ Q2W/Q4W (49), and BKZ Q4W/Q4W (47) groups vs PBO (27). To Wk16, the total number of days patients achieved HiSCR75/90 was at least double in the BKZ groups vs PBO. To Wk48, total number of days with HiSCR50 achievement: BKZ Q2W/Q2W, 211; BKZ Q2W/Q4W, 212; BKZ Q4W/Q4W, 206 vs PBO/BKZ Q2W, 178. Comparable results were observed for HiSCR75/90 at Wk48, with BKZ groups maintaining higher responses vs PBO.
Conclusion: High levels of cumulative clinical benefit were observed for patients on BKZ through Wk16; benefits increased substantially through Wk48. The cumulative benefit of BKZ through 48wks was evident for patients receiving continuous BKZ and PBO switchers. The total number of days of clinical outcome achievement remained higher in those on continuous BKZ vs PBO switchers. These results demonstrate the rapid, high-level and durable responses that can be obtained with BKZ.

Barriers and facilitators to quality HS biologic care and outcomes for the Medicaid population across US states

2024-11-07T15:36:01+00:00

Introduction: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by painful skin lesions and dermal abscesses.¹ US-based patients with HS are often covered by Medicaid (21.6–31.0%)^2–5with substantial state-by-state variations in coverage. Barriers to accessing biologics for HS may delay treatment and worsen patient outcomes. Here, we report differences in Medicaid criteria to access biologic care for HS across all 50 US states.

Procedure/study: A qualitative review of the Medicaid Utilization Management (UM) policies for biologic use in HS was conducted. Data were collected from the Medicaid UM policies, Medicaid websites, and Managed Medicaid UM policies of each state in February 2024. All 50 states were analyzed; barriers to access and discrepancies across state Medicaid UM policies were identified, and opportunities to address these discrepancies in the form of an HS coalition were recognized. The analysis stratified the Medicaid UM criteria for each state for treatment with a biologic (adalimumab/secukinumab) into no or low, medium, and high barrier levels. For high barrier level states, comparison with UM criteria for psoriasis was made.

Results: Overall, the UM policies varied widely, and burdensome barriers to biologic care were identified in some states. In total, 40 states had no or low barrier criteria; states with low barrier criteria required an HS diagnosis and a prescription, or inadequate responses to ≥1 therapy (steroids/antibiotics). Alabama, Kentucky, Minnesota, Missouri, Ohio, Oregon, Pennsylvania, and Washington had medium barrier criteria and generally required an HS diagnosis and failure with ≥2 therapies. Here, criteria may be reduced to align with low barrier states. Iowa and Oklahoma had high barrier criteria. Both required ≥3 abscesses or inflammatory nodules, an HS diagnosis with Hurley Stage II/III, and failure with ≥2 therapies. In Iowa, eligible requests received three months treatment, with additional authorizations conditional upon ≥50% reduction in abscess and nodule count. The approval criteria of biologics for psoriasis were less stringent than HS in Iowa and Oklahoma, including fewer criteria items and therapy failures: Iowa ≥2 vs ≥3; Oklahoma ≥1 vs ≥2.

Conclusion: Substantial state-by-state variations in Medicaid criteria were observed, with ten out of 50 states having medium to high barriers to accessing biologics. Large disparities in criteria for access to biologic care between psoriasis and HS were observed in two states. These barriers and discrepancies represent opportunities for an HS coalition at the state level, to improve access to care and patient outcomes.⁶

Microwave Energy for Managing Hidradenitis Suppurativa

2024-11-10T21:31:41+00:00

Title: Microwave energy for managing Hidradenitis Suppurativa

Nicole Bielecki PA-C and Aaron Hoover MD

Front Range Dermatology, Greeley, CO 80634

Introduction:

Treating hidradenitis suppurativa (HS) is challenging due to its chronic, recurring nature and resistance to conventional therapies like antibiotics, anti-inflammatories, and surgery. Even with new biological treatments, there are challenges with injection site reactions. The associated pain, drainage, malodor, and scarring also significantly impact patients' mental well-being, underscoring the need for novel treatments. Four cases presented here suggest that microwave energy (ME) therapy can reduce pain, erythema and inflammation in HS lesions and even assist to resolve moderate and smaller lesions. Precise and brief surface-based applications of microwave energy to HS lesions from an FDA-cleared microwave device intended for the coagulation of soft tissue were used to generate localized hyperthermic conditions in HS and pre-HS lesions. The rapid heating of the tissues led to subsequent clearance of moderate and small HS lesions. This was accompanied with a reduction in inflammation, draining and pain associated with these HS cases. While the outcomes are promising, the exact mechanism of action needs further investigation. These cases strongly support further research and demonstrate that ME holds promise as a novel, non-invasive treatment modality for the management of HS.

Procedure:

A total of 25 HS lesions from five patients were treated with ME energy. Five repetitive 2-second pulses of 3 to 4W of ME operating at 8GHz were applied to the full area of these lesions. Three to four treatment sessions were given ranging from 7 to 14 days apart. Two patients received ME as a monotherapy, whereas the others began regimens of isotretinoin, adalimumab, or secukinumab at the same time as the first ME treatment.

Results:

These five patient cases demonstrate how ME treatments can lead to a rapid reduction in reported pain and erythema as well as clinical-assessed clearance of several early and moderate state HS lesions. Two of these patients only received ME as a monotherapy. However, based on clinical experience, even patients typically on medications will not typically show improvements within 7-14 days, suggesting that ME was having a rapid impact to manage pain and inflammation associated with HS lesions and in some cases assisting to resolve these lesions entirely.

Conclusions:

These cases report the first step in clinical feasibility and safety of microwave energy and shows promise as a novel modality for the management of HS. Although still in the early days of feasibility work, this non-invasive, fast, well-tolerated and simple treatment of microwave energy shows promise as a novel modality for the management of HS.

Financial support: This work was supported by Emblation Ltd.

Novel Approach to Fat Reduction: A Phase I Study Evaluating Safety and Tolerability of STP705 in Abdominoplasty

2024-10-31T17:19:34+00:00

Background: RNAi therapeutics are a rapidly developing technology with broad medical applications predicated on reducing the expression of genes with key links to disease pathogenesis. The TGF-β1/Smad3 and COX-2 signaling pathways are strongly implicated in obesity and type 2 diabetes. Reducing the expression of TGF-β1 and COX-2 may have benefits in fat reduction procedures. The aim of this study was to assess the safety and tolerability of STP705 (a TGF-β1/COX-2 siRNA complex in a polypeptide nanoparticle vehicle) injections in persons undergoing abdominoplasty. A secondary aim was to make initial histologic observations on the efficacy of STP705 injections in inducing adipocyte apoptosis for the purpose of focal fat reduction.

Methods: The study treatment consisted of 3 rounds of treatment with 7 subcutaneous abdominal injections of STP705 or placebo. Eight female subjects aged 18-65 years received 120 μg, 240 μg, or 360 μg STP705 in 0.5 or 1.0 ml doses (per injection) or an equivalent amount of placebo injected randomly across seven 1 cm² areas. Treatments were administered 28 days apart with follow-ups occurring at 2 and 7 days’ post-procedure. Tissue samples from each of the 7 injection sites were harvested from total abdominoplasty excisional specimens obtained 28 days after the final injection. Safety assessments were conducted, including physical examination, clinical laboratory tests, electrocardiograms, evaluation of local skin reactions (LSRs), and collection of adverse events (AEs). Lipolytic and inflammatory effects of STP705 were assessed by blinded histologic analysis of harvested tissue samples.

Results: There were no clinically significant changes in clinical labs, vital signs, or ECGs. The incidence of LSRs was low throughout the study. There were 3 moderate AEs deemed likely to be related to STP705 injection; none required intervention, and all resolved without dose modification. Histology revealed marginally dose-dependent tissue response with adipocyte destruction and fat remodeling.

Conclusion: In general, STP705 was well tolerated at all concentrations and volumes studied. STP705 demonstrated excellent safety, and initial histologic analysis is suggestive of its efficacy in adipocyte destruction. The lack of cutaneous side effects with STP705 injection is an advantage over current treatments for similar indications.

In a prospective, multicenter study, the 31-GEP identified patients at increased risk of tumor recurrence and added significant prognostic value to AJCC staging

2024-11-06T15:30:17+00:00

Cutaneous melanoma (CM) guidelines base management decisions on a patient’s American Joint Committee on Cancer (AJCC) tumor stage. However, limitations in staging accuracy suggest additional tools could improve risk-aligned patient management decisions. The 31-gene expression profile (GEP) test identifies patients with CM with low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk for sentinel lymph node (SLN) positivity, recurrence, metastasis, and death. In this multicenter, prospective study, we validated the 31-GEP for risk of recurrence and demonstrated the added value of 31-GEP to AJCC staging.

Patients were included in the prospective CONNECTION study if they were tested with the 31-GEP from 2018 to the present (n=876). Survival was estimated using Kaplan-Meier analysis and 31-GEP stratification tested with the log-rank test. Cox regression was performed to identify predictors of recurrence. ANOVA was used to compare Cox models for the most accurate recurrence prediction.

Patients with a Class 1A result had significantly higher 3-year recurrence-free survival than those with a Class 1B/2A or Class 2B result (98.5% vs. 80.8% vs. 63.0%, p<0.001). The 31-GEP had higher sensitivity (75.0% vs. 37.5%) and negative predictive value (98.6% vs. 96.9%) than AJCC staging. Multivariable analysis demonstrated that Class 1B/2A (hazard ratio, HR=3.12, p=0.037) and Class 2B (HR=5.91, p=0.002) were significant predictors of recurrence in addition to stage IB (HR=4.02, p=0.02), IIA (HR=6.06, p=0.006), IIC (HR=17.14, p<0.001), and III (HR=8.84, p<0.001). Stage IIB (HR=4.63, p=0.057) was not significant. Comparing a staging-only model to a 31-GEP+staging model showed that adding 31-GEP to staging significantly improved prediction accuracy over staging alone (ANOVA: c2=10.58, p=0.005).

In this prospective study, the 31-GEP stratified risk of recurrence, was a significant predictor of recurrence, and added significant predictive value to AJCC staging. The 31-GEP identifies patients at high risk of recurrence who should be managed more intensely, and adding 31-GEP to staging allows better risk-aligned care decisions, which can lead to improved patient outcomes.

A Non-Prescription Nitric Oxide Releasing Gel Demonstrates In Vitro Anti-fungal Activity and Supports Nail Clearance in Patients with Onychomycosis

2024-11-08T23:54:24+00:00

Background: Onychomycosis is a common fungal nail infection. Nitric oxide has broad-spectrum antifungal activity; NO releasing formulations are in development to support nail wellness.

Objective: to examine antifungal properties of NO releasing formulations liquid (NORS) and gel (NORS-gel) to support nail clearance in onychomycosis.

Methods:

NORS In Vitro antifungal testing: Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were used to compare NORS with efinaconazole. Trichophyton tonsurans, Trichophyton mentagrophytes, and Epidermophyton floccosum were selected and MFC was performed. Cidal activity: ≥ 99.9% reduction in CFUs/mL from baseline; Static activity: <99.9% reduction from baseline CFU/mL. (CFU: colony forming units).

NORS keratin binding: Six tubes were prepared with 1 mL + 10⁷conidia/mL of T. mentagrophytes strain (37035) + sterilized cadaver nail; six treatment tubes included: NORS, NORS+Keratin (50mg/mL), Terbinafine (0.002 µg/mL)+keratin (50 mg/mL), Terbinafine (0.002 µg/mL), Growth control (T. mentagrophytes+saline). After 15-min, tubes were centrifuged, supernatant decanted, and pellets resuspended in sterile saline; 10-fold serial dilutions were plated (triplicate).

Ex-Vivo in Onychomycosis: Toenail samples from patients with suspected onychomycosis were shredded and either placed onto agar plates incubated at 30°C for 1-month, or, treated with 1.5mL NORS-gel to 50mL tube, placing the clippings onto the gel and then overlaying another 1.5mL NORS-gel, samples were stored in the dark at room temperature for 8-hours, washed, dried, plated and incubated at 25°Cx7days

Nail penetration: Underside of cadaver toenails were inoculated with T. mentagrophytes 10⁷conidia/mL and placed on inert gel agar. A bead of NORS-gel (approx. 0.125mL), control gel and Terbinafine 0.002 µg/mL were spread to cover the topside of the nail. Covered petri dishes were placed for 15-minutes and 8-hours; the nail was removed, washed 3x in sterile saline, and pulverized; serial dilutions with plated samples incubated at 25°Cx7days. Statistics: Log CFU ± standard deviation, analyzed by t-test, p ≤ 0.05.

Human Volunteers: Three individuals with confirmed onychomycosis applied daily NORS-gel to infected nails (covered overnight), for one month. Photographs were taken at baseline, day 1 after application, and 4-5 months post-application. Volunteers self-reported nail appearance.

Results:

NORS In Vitro antifungal testing: NORS showed potent antifungal activity against dermatophytes, including those less susceptible to efinaconazole.

NORS keratin binding: NORS with and without keratin demonstrated the lowest fungal burdens with average log CFUs/mL ± SD of 0 ± 0, and 2.45 ± 0.5, respectively, demonstrating significant activity vs control, and terbinafine (P-values < 0.0001).

Ex Vivo: NORS-gel demonstrated significant fungicidal activity as indicated by the absence of fungal growth on petri dishes.

Nail penetration: NORS-gel treated nail showed no fungal growth (average log CFUs/g ± SD of 0 ± 0) vs. terbinafine–burden of 3.58 ± 0.2 average log CFU/g, at 8 hrs. NORS-gel significantly reduced fungal burden vs. terbinafine and control (P-value < 0.05). (preliminary results; methodology undergoing refinement.)

Human Volunteers: Daily application of NORS-gel for one-month improved nail clarity in volunteers with confirmed onychomycosis. Temporary discoloration was observed during treatment.

Conclusions: NORS and NORS-gel demonstrated antifungal activity; NORS-gel supported nail clearance and was well tolerated in individuals with onychomycosis.

Dupilumab Improves Patient-Reported Outcomes as Early as 1 Month among Adults with Prurigo Nodularis in Clinical Practice: Initial Results from the RELIEVE-PN Study

2024-11-08T06:21:44+00:00

Introduction: Dupilumab is a monoclonal antibody approved in the United States (US) for patients aged ≥18 years with prurigo nodularis (PN). This analysis evaluated the real-world initial impact of dupilumab therapy on symptoms and treatment satisfaction among US adults with PN. Methods: RELIEVE-PN is an ongoing longitudinal prospective patient survey study assessing the real-world effectiveness of dupilumab in the treatment of adult patients with PN. Adults with PN were recruited through the US dupilumab patient support program and surveyed before (baseline) and 1 month after dupilumab initiation. PN symptoms over the last 7 days were assessed using the worst-itch numeric rating scale (WI-NRS), average-itch NRS, skin pain NRS, and skin burning or stinging/tingling NRS (range 0 [no symptom] to 10 [most severe symptom] for all). Treatment satisfaction with current therapy was evaluated using a 7-point Likert scale from “extremely satisfied” to “extremely dissatisfied”. Results: Of 84 patients (mean age, 57.5 years; 79.8% female; 83.3% White) completing the baseline survey and initiating dupilumab, 62 (mean age, 56.4 years; 77.4% female; 83.9% White) completed the Month 1 survey. At baseline, mean (SD) WI-NRS, average itch NRS, skin pain NRS, and skin burning/tingling NRS were 7.70 (2.24), 6.45 (2.25), 5.06 (2.87), and 5.51 (3.02), respectively. By month 1, mean (SD) WI-NRS, average itch NRS, skin pain NRS, and skin burning or stinging/tingling NRS improved to 5.56 (2.89), 4.35 (2.23), 3.40 (2.46), and 3.76 (2.60), respectively (p<0.001 for all). Additionally, significantly more patients reported they were satisfied with current PN treatment(s) at 1 month after dupilumab treatment initiation vs prior to starting dupilumab (77.4% vs 13.1%; p<0.001). Conclusion: Early results from the RELIEVE-PN study demonstrate improvement in symptoms and patient satisfaction with therapy as early as 1-month from treatment initiation of dupilumab. Further comparative research is needed to confirm these findings.

Acknowledgment: Research was funded by Sanofi and Regeneron Pharmaceuticals Inc.

TONE: A Large, Prospective Post-Approval Study Investigating the Repigmentation of Stable Vitiligo Lesions Using a Point-of-Care Autologous Cell Harvesting Device

2024-10-31T16:27:27+00:00

Introduction: Vitiligo is a depigmenting autoimmune skin disorder caused by loss of melanocytes, impacting 0.5% to 2% of the global population.^1-3 For patients with stable vitiligo, surgery allows for physical transplantation of healthy melanocytes to a lesion lacking functional melanocytes.^1,4 A combination approach incorporating vitiligo surgery with pharmacotherapy may be recommended in some patients, as employing multiple modalities can improve repigmentation response.⁴ A point-of-care Autologous Cell Harvesting Device, FDA-approved for the repigmentation of stable vitiligo lesions, prepares autologous skin cell suspension (ASCS) to be applied onto laser-ablated lesions.⁵ Previously reported, the randomized, within-subject controlled pivotal trial found that 36% of ASCS-treated lesions achieved ≥80% repigmentation at 24 weeks post-treatment, versus 0% of control lesions.⁶ Here, we report on TONE, a post-approval trial using this device.

Objective: This multi-center, prospective study was conducted to evaluate repigmentation response following the application of ASCS in patients with stable vitiligo lesions in a large study population.

Methods: Enrolled patients had to have a previous unsatisfactory response to topical treatments or phototherapy, have vitiligo comprising <30% body surface area, and remain on their current use of concomitant vitiligo treatment (if applicable) for the duration of the study. A vitiligous area was identified for laser ablation and ASCS treatment, followed by at-home narrowband ultraviolet-B (NB-UVB) phototherapy. Repigmentation response at 24 weeks post-treatment was assessed by a Central Review Committee of three blinded, independent dermatologists.

Results: A total of 107 patients were treated across 17 U.S. sites (14 in-office, 3 hospital outpatient). Enrolled patients had a mean age of 47 (SD±14.6), and half were female. Most patients had non-segmental vitiligo (n=68, 64%), while 17% (n=18) had segmental vitiligo and 20% (n=21) had focal vitiligo.The majority (n=74, 68%) were White, followed by 14% Asian (n=16), and 4% Black or African American (n=5); 29% (n=32) of patients identified as Hispanic or Latino. Three percent (n=3) of patients were Fitzpatrick type I, with 23% (n=25) type II, 43% (n=46) type III, 20% (n=21) type IV, 9% (n=10) type V, and 2% (n=2) type VI. Fifty-two (49%) patients reported using concomitant medication(s) for their vitiligo throughout the study. At Week-24, 42% (n=42) of assessed treated areas achieved ≥80% repigmentation. No serious or severe device-related adverse events were reported.

Conclusion: These results are consistent with findings previously reported in the randomized controlled pivotal trial.⁶ This study provides further evidence confirming the safety and effectiveness of ASCS for the repigmentation of stable vitiligo lesions, as demonstrated in a large patient population. A diverse population was represented in the large patient sample with an even distribution of male and female patients, inclusion of various vitiligo sub-types, representation of all Fitzpatrick skin types I-VI, and incorporation of concomitant therapies into the protocol. This diversity among subjects is in-line with reported vitiligo patient population data,^3,4 indicating potential for generalizability of study findings in practical real-world applications.

Clinical Efficacy of a New Moisturizer Containing Ceramides and Natural Moisturizing Factors on Subjects with Extra Dry, Itchy Skin

2024-11-05T20:51:06+00:00

N/A

Results of a Phase 2 Multicenter Study Evaluating the Safety and Tolerability of VP-315, an Investigational Therapy for Basal Cell Carcinoma

2024-10-31T19:36:50+00:00

Introduction

VP-315 is an intratumorally injected, chemotherapeutic oncolytic peptide in development as a non-surgical immunotherapeutic agent to be utilized as first line therapy in a primary or neoadjuvant setting for patients with basal cell carcinoma (BCC).

Objective

In Part 2 of this study, the primary objective was to determine the optimal dosing regimen for VP-315 by exploring the effects of various dosing schemes on the safety and tolerability of VP-315 in a larger population of subjects with biopsy proven BCC.

Methods

Eighty-two (82) subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme:

Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose).

Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose).

Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*).

Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*).

* Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later.

Safety and tolerability were assessed by documenting the occurrence of Treatment Related Adverse Events (TRAEs), including those of special interest, Treatment Related Serious Adverse Events (TRSAEs), discontinuations due to AEs and expected treatment-related cutaneous reactions including tumor necrosis.

Results

All 82 subjects completed one of the VP-315 treatment regimens for BCC. TRAEs were mostly mild to moderate. AEs included injection site pain (mild 13.4%, moderate 12.2%, severe 1.2%), hypertension (mild 4.9%), hypotension (mild 4.9%), erythema (mild 1.2%, moderate 2.4%), and headache (mild 2.4%). Expected cutaneous reactions were observed. No TRSAEs were reported.

Conclusion

VP-315 treatment was shown to be safe and well-tolerated when administered once daily 2-3 times per week per tumor for up to 2 weeks using a split dose approach. Given its favorable safety profile, VP-315 warrants continued research as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting.

Sponsored by Verrica Pharmaceuticals Inc.

Results of a Phase 2 Multicenter Study to Evaluate the Efficacy of VP-315, an Investigational Therapy for Basal Cell Carcinoma

2024-10-31T19:19:59+00:00

Introduction: VP-315 is an intratumorally injected, chemotherapeutic oncolytic peptide in development as a non-surgical immunotherapeutic agent to be utilized as first line therapy in a primary or neoadjuvant setting for patients with basal cell carcinoma (BCC).

Objective: In Part 2 of this study, the secondary objective was to evaluate the effect of various dosing regimens on the antitumor efficacy of VP-315 in a larger population of adult subjects with biopsy proven BCC.

Methods: Eighty-two (82) subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme:

Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose).

Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose).

Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*).

Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*).

* Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later.

Efficacy endpoints included histological clearance of target tumor(s) and estimate of remaining tumor volume (tumor size reduction) at excision (Week 12-13).

Results: Eighty-two (82) subjects (n=92 lesions) completed treatment for BCC with VP-315 in Part 2. Approximately 51% of tumors achieved complete histologic clearance. All tumors treated had a reduction in tumor size. Overall tumor size reduction was 86%. Tumor size reduction in subjects who still had any residual tumor was 71%.

Conclusion: Complete histological clearance in a majority of VP-315 treated tumors could eliminate the need for surgical intervention in those patients in clinical practice. In subjects with residual tumor burden, the substantial reduction in tumor size after VP-315 treatment would markedly reduce the surgical incision area and the amount of potential post-surgical scarring. Based on the favorable results, further research using VP-315 as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting is warranted.

Microwave Energy for Treatment of Superficial and in situ Squamous Cell Carcinoma

2024-10-31T17:08:04+00:00

n/a

Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by blue light in the treatment of facial cutaneous squamous cell carcinoma in situ

2024-10-31T17:07:24+00:00

Background: Cutaneous squamous cell carcinoma in situ (isSCC) is a common skin cancer occurring from sun exposure and often appears on the face. Treatment is primarily surgical but less invasive treatments are desirable. Currently, aminolevulinic acid for photodynamic therapy (ALA-PDT) is approved in the US and Canada for the treatment of single and multiple non-hyperkeratotic actinic keratoses of the face and scalp. This study evaluated the safety, tolerability, and efficacy of ALA-PDT for treatment of facial isSCC.

Methods: Thirty-two patients with biopsy-confirmed isSCC on the face were recruited. Lesions 0.4–1.3 cm in diameter were included. Per the actinic keratosis treatment protocol, the lesion was debrided with a 4 x 4 gauze and ALA 20% topical solution was applied to the lesion and adjacent skin and incubated for 18–24 hours, followed by blue light therapy 16 minutes 40 seconds at 10 J/cm2. Patients underwent two treatments with ALA-PDT spaced 28 +/- 3 days apart. The area of the original lesion was excised eight weeks following the second treatment for histopathological assessment. The primary efficacy endpoint was the complete absence histologically of the isSCC at end of treatment. The secondary efficacy endpoint was the achievement of clinical clearance of the skin lesion. Safety assessment was done through adverse events and local skin reactions (LSRs; erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) and site pain within 15 minutes of each treatment session.

Results: Of the 32 patients enrolled, two did not complete the study. No residual SCCis was detected in 30/30 (100%) patients. Clinical clearance was achieved in 30/30 (100%) of the patients by the end of treatment. None of the patients experienced related adverse events and only 2/30 (5%) experienced an AE of hypertension and was considered to be unrelated. The most common LSRs were erythema and scaling and were primarily mild, seen to occur immediately after both treatments and diminished over time. The average median ± SD immediate post-treatment pain score was 2.56 ± 2.15 on the VAS scale.

Conclusion: The ALA-PDT protocol outlined in this study appears to be a very effective, safe and well-tolerated treatment option for isSCC on the face.

Expert Consensus-Based Recommendations on the Use of Photodynamic Therapy in Actinic Keratosis Patients

2024-11-06T16:11:16+00:00

Expert Consensus-Based Recommendations on the Use of Photodynamic Therapy in Actinic Keratosis Patients

Vishal A. Patel, MD¹; Sarah T. Arron, MD²; Brian Berman, MD, PhD³; M. Shane Chapman, MD, MBA⁴; Anokhi Jambusaria-Pahlajani, MD⁵; George Martin, MD⁶; Anthony M. Rossi, MD⁷; Todd Schlesinger, MD⁸; Nathalie C. Zeitouni, MDCM⁹; Neal Bhatia, MD¹⁰

¹Department of Dermatology, George Washington University School of Medicine & Health Sciences, Washington, DC; ²Peninsula Dermatology, Burlingame, CA; ³University of Miami Miller School of Medicine, Miami, FL; Center for Clinical and Cosmetic Research, Aventura, FL; ⁴Department of Dermatology, Dartmouth Hitchcock Medical Center, Nashua, NH; Geisel School of Medicine at Dartmouth, Lebanon and Hanover, NH; ⁵Division of Dermatology, Department of Internal Medicine, The University of Texas at Austin Dell Medical School, Austin, TX; ⁶Dr. George Martin Dermatology Associates, Kihei, HI; ⁷Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY; New York Presbyterian Hospital, New York, NY; ⁸Clinical Research Center of the Carolinas, Charleston, SC; ⁹Medical Dermatology Specialists, Phoenix, AZ; University of Arizona COM, Phoenix, AZ; ¹⁰Therapeutics Clinical Research, San Diego, CA

Background: Actinic keratoses (AKs) are common premalignant skin lesions that can progress to cutaneous squamous cell carcinomas, especially in individuals who have a history of prior AK diagnoses. Photodynamic therapy (PDT) is an effective and safe treatment for AKs and can treat large areas of field cancerization. While there are existing AAD guidelines published on the treatment of AKs, the authors wanted to further explore the treatment of AKs with PDT.

Methods: A systematic literature review surrounding PDT and AK was performed using PubMed, pulling relevant articles from between 1990-2023 using exploded Medical Subject Heading (MeSH) terms and keywords. Based on these articles, consensus statements were developed by professional medical writers. Ten expert dermatologists were recruited for this consensus group. An electronic questionnaire with the consensus statements were sent to panelists to vote on using a modified Delphi method. Each panelist was asked to rate each statement on a three-point Likert-type scale of disagree, slightly agree and strongly agree. For consensus to be established, ≥70% of panelists must strongly agree on the statement. If the threshold was not reached, the statement was revised and sent out for another round of voting. An anonymous virtual meeting was convened to discuss outstanding statements.

Results: A total of ten dermatology experts were recruited for the consensus group and a total of three rounds of voting were completed. An anonymous virtual meeting was convened in December 2023 after two rounds of voting to discuss and amend outstanding statements. A total of 55 consensus statements were established in many facets of PDT in AK, including lesion vs. field-directed therapy, cosmetic outcomes, patient selection, patient preference, choice of photosensitizer, incubation time, light source, painless PDT protocols, and PDT in organ transplant recipients and the elderly. A select number of consensus statements are presented.

Conclusion: Through this consensus group, we were able to develop a more comprehensive set of recommendations for the use of PDT in AKs. These recommendations can provide guidance for clinicians and bridge gaps in existing knowledge.

This study was funded by an unrestricted grant from Biofrontera, Inc.

Safety and Efficacy of Photodynamic Therapy with ALA 10% Topical Gel Activated by Red Light versus ALA 20% Topical Solution Activated by Blue Light for the Treatment of Actinic Keratosis on the Upper Extremities: A Blinded Randomized Study

2024-11-06T16:27:56+00:00

Background: Actinic keratosis (AKs) is a pre-cancerous skin neoplasm that can appear as erythematous to pink scaly plaques at sites of ultraviolet light damage. Photodynamic therapy (PDT) using aminolaevulinic acid (ALA) 10% gel activated by red light is approved by the FDA for the treatment of AKs on the face and scalp, and ALA 20% solution activated by blue light is approved for PDT treatment of AKs on the face, scalp, and upper extremities. While both options have been proven to an effective treatment on the upper extremity, there has been no direct side-by-side comparison. This study aimed to compare the safety and efficacy of both PDT on the upper extremities.

Design: This was a prospective, single-center, split-arm randomized clinical trial with 20 adult subjects presenting with 4-17 clinically confirmed mild-moderate AKs (Olsen grading) on each distal upper extremity. Subjects were treated with ALA 10% gel/red light and ALA 20% solution/blue light PDT on respective randomly selected upper extremities. Lesion complete clearance rate (LCCR) served as the primary endpoint. Secondary endpoints included complete clearance per patient side (PatCR), LCCR of moderate lesions, LCCR 12 weeks after PDT-1, PatCR 12 weeks after PDT-1, overall cosmetic outcome assessed by the investigator, and patient satisfaction.

Results: The LCCR was significantly greater for ALA10% vs. ALA20% at Day 120; no significant differences were observed at the other observed time points. 30 patients were enrolled in the study and received their first treatment (PDT1). LCCRs after PDT1 were 65.4% and 58.4% for ALA10% and ALA 20%, respectively. 25 patients received a second treatment (PDT2), resulting in LCCRs of 88.2% and 72.1% respectively. 22 patients returned for follow-up 6 months after their last PDT treatment (PDT1 or PDT2), with LCCR of 83.7% (ALA10%) and 79.3% (ALA20%). 17 patients returned for follow-up 12 months after the last PDT treatment, with LCCRs of 81.5% (ALA10%) and 87.6% (ALA20%). There were no statistical differences between ALA10% and ALA20% for subject-reported pain or satisfaction ratings. ALA10% was rated as significantly easier to apply compared to ALA20% by the investigator.

Conclusion: Both ALA10% and ALA20% appear to be safe and effective for PDT treatment of AKs on the upper extremities. There is a trend for increased efficacy with ALA10%, and it may be easier to apply. Additional data is in the process of being collected as the study continues.

Pilot study utilizing short contact protocols for treatment of actinic keratoses (AK) with ALA gel-red light photodynamic therapy (PDT)

2024-11-06T16:38:46+00:00

Background: Red light photodynamic therapy (PDT) is an effective option for actinic keratosis (AK) lesions. However, stinging pain during illumination limits utility.

Objective: To compare three modified red-light PDT regimens (short incubation, whole-face application, no occlusion) and to determine whether these can reduce pain yet still provide significant AK lesion clearance.

Methods: Patients in this randomized clinical trial (n = 30) were randomized into one of three groups [incubation with 10% ALA gel, illumination with red-light]: Group A: 10 min, 20 min (75 J/cm²); Group B: 20 min, 10 min (37 J/cm²); Group C: 1 hour, 10 min (37 J/cm²). Two PDT treatments were administered 8 weeks apart. Lesions were counted at each visit, and pain was recorded on a scale from 0 – 10.

Results: Patients Groups A and B (shorter incubations) experienced significantly less pain during illumination than Group C. After one treatment, the AK lesion reduction in Group A (59%) was statistically non-inferior to Group C (43%), with a noninferiority margin of ±15%. Final lesion counts after two PDT treatments showed a reduction from baseline by 82% in Group C, 76% in Group A, and 74% in Group B. Groups A and B did not meet the statistical non-inferiority endpoint relative to Group C after two treatments.

Limitations: Small sample size, which limited the ability to reach statistical significance after 2 PDT treatments.

Conclusion: Two short/modified red light PDT regimens were essentially painless, and all three provided AK lesion clearances comparable to conventional regimens.

Dermal and Systemic Pharmacokinetics of Oral DFD-29 (minocycline hydrochloride modified release capsules, 40 mg) vs Oral Doxycycline 40 mg in Healthy Subjects

2024-11-04T21:22:05+00:00

Dermal and Systemic Pharmacokinetics of Oral DFD-29 (minocycline hydrochloride modified release capsules, 40 mg) vs Oral Doxycycline 40 mg in Healthy Subjects

Adelaide A. Hebert, MD,¹ Srinivas Sidgiddi, MD²

¹UTHealth Houston McGovern Medical School, Houston, TX; ²Journey Medical Corporation, Scottsdale, AZ

Introduction: A modified-release, low-dose formulation (DFD-29) of minocycline hydrochloride (HCl) is under investigation for the treatment of rosacea. This Phase 1 study compared the dermal and systemic pharmacokinetics of DFD-29 (minocycline HCl, 40 mg) and doxycycline 40 mg in healthy, adult subjects.

Methods: This randomized, open-label, single-center, parallel-group study evaluated the systemic and dermal pharmacokinetics of once-daily administration of oral DFD-29 40 mg capsules or oral doxycycline 40 mg for 21 days in healthy adult volunteers. On Day 1, subjects received the assigned study drug under fasting conditions. Blood was sampled before drug administration, every 30 minutes for 4 hours, hourly for 4 hours, and 12 and 24 hours post dose. Dermal interstitial fluid (ISF) was sampled using three open-flow microperfusion probes before dosing, hourly for 8 hours, and at 11-12, 15-16, and 23-24 hours post dose. After discharge, subjects continued to take assigned study drug once daily through Day 21, when they returned to the center and underwent the same procedures as on Day 1. Safety was evaluated by monitoring adverse events (AEs), vital signs, and laboratory tests.

Results: A total of 24 subjects were randomized and completed the study. On Day 1, mean plasma C_max levels with DFD-29 (382.8 ng/mL) and doxycycline (405.9 ng/mL) were comparable (Pr > 0.716). By Day 21, mean plasma C_max had nearly doubled with doxycycline but remained constant with DFD-29 (701.9 vs 337.7 ng/mL; Pr > 0.037). Mean plasma AUC was also significantly greater with doxycycline than with DFD-29 at Day 21 (6074.8 ng.hr/mL vs 3957.6 ng.hr/mL, Pr > 0.013). In contrast, mean dermal C_max concentrations were numerically higher with DFD-29 (40 mg) than doxycycline at Day 1 (109.7 vs 81.5 ng/mL; Pr > 0.117) and Day 21 (125.7 vs 114.7 ng/mL; Pr > 0.681). The mean dermal AUC at Day 1 also was greater with DFD-29 than with doxycycline (1412.29 ng.hr/mL Vs 1088.55 ng.hr/mL, Pr > 0.213), and at Day 21 it was similar in the two groups (1604.77 ng.hr/mL for DFD-29 and 1573.63 ng.hr/mL for doxycycline, Pr > 0.954). Both DFD-29 and doxycycline 40 mg were well tolerated by the healthy volunteers.

Conclusion: Minocycline from DFD-29 with its modified-release formulation provides higher dermal concentration than doxycycline from Day 1 onwards at a similar dose. The higher concentration from Day 1 at the site of action is expected to translate into a clinically meaningful impact in the treatment of patients with rosacea.

This study and abstract are funded by Journey Medical Corporation.

Efficacy and Safety of Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Participants with Moderate-to-Severe Acne: The Patient Journey

2024-11-06T19:24:31+00:00

Introduction: The main goal of acne treatment is to clear lesions quickly to manage and/or mitigate sequelae. Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the only fixed-dose, triple-combination approved for acne. In three published clinical studies of participants with moderate to severe acne, CAB gel demonstrated superior efficacy to vehicle and component dyads, with good safety/tolerability. Herein are presented detailed efficacy and safety data from 5 clinical study patients to document their CAB treatment journey.

Methods: In two phase 3 (NCT04214652, NCT04214639), double-blind, 12-week studies, participants aged ≥9 years with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel. Endpoints included percentage of participants achieving treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) and percent change from baseline in inflammatory/ noninflammatory lesion counts. Dosing compliance, treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were also assessed. Descriptive data from 5 selected cases who completed 12 weeks of CAB treatment are summarized.

Results: Participants (n=5) ranged from 13-32 years. At week 12, 3 achieved treatment success, 1 achieved a 2-grade reduction from severe to mild, and 1 achieved a 1-grade reduction from moderate to mild. Reductions from baseline to week 12 in inflammatory/ noninflammatory lesion counts ranged from 74.7-100%. No participants reported TEAEs/serious AEs. Some cutaneous safety/tolerability scores increased at weeks 2, 4, or 8, but generally decreased back to/below baselines levels by week 12, similar to the overall study populations. Most scores at week 12 were 0 (none) or 1 (mild), with only one participant reporting scores of 2 (moderate) for itching, burning, and stinging.

Conclusions: In the overall phase 3 clinical trials, fixed-dose, triple-combination CAB gel has demonstrated good efficacy, safety, and tolerability. All 5 cases presented here achieved substantial (>70%) acne lesion reductions, with 4/5 cases achieving treatment success or a 2-grade EGSS reduction by week 12. While patterns in cutaneous safety/tolerability were variable across cases, transient increases with CAB generally resolved to baseline values within two months of treatment. These clinical study cases reinforce the importance of patient education regarding efficacy and safety of acne treatment, including the importance of treatment adherence, managing patient expectations, and the potential for cutaneous effects, which are often transient.

Support: Ortho Dermatologics

Efficacy and Safety of Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Black Participants with Moderate-to-Severe Acne

2024-11-06T19:51:10+00:00

Introduction: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the first fixed-dose, triple-combination formulation approved for the treatment of acne, and is indicated in patients 12 years of age and older. In 3 clinical studies of participants with moderate-to-severe acne, CAB gel demonstrated superior efficacy to vehicle and component dyads, with good safety/tolerability. To better understand the efficacy and safety of CAB gel in patients with darker skin phototypes, this post hoc analysis included participants who self-identified as ‘Black or African American’ (hereafter referred to as Black).

Methods: Data were pooled from a phase 2 (N=741) and two phase 3 (N=183; N=180), double-blind, randomized, 12-week studies. Participants aged ≥9 years with moderate to severe acne were randomized to receive once-daily CAB or vehicle gel. Endpoints included ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in inflammatory/ noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were also assessed.

Results: Of 657 participants randomized to CAB or vehicle gel, 104 (15.8%) self-identified as Black (n=64 CAB, n=40 vehicle). At week 12, 31.5% of Black participants treated with CAB achieved treatment success, compared to 17.3% with vehicle. Inflammatory lesion reductions with CAB were significantly greater than with vehicle
(69.0% vs 53.6%, P<0.01), and noninflammatory lesion reductions were numerically greater with CAB than with vehicle (58.3% vs 51.9%). The rate of TEAEs with CAB treatment in Black participants was generally lower than in the overall study population (23.4% vs 24.6-36.2%), and most TEAEs were of mild-to-moderate severity.

Conclusions: Fixed-dose, triple-combination CAB gel was efficacious and well tolerated in Black participants with moderate-to-severe acne. Despite the limited number of self-identified Black participants across the clinical studies of CAB gel, these post hoc analyses add valuable information to the limited literature describing treatment effects of fixed-dose combination acne treatments in Black individuals.

Funding: Ortho Dermatologics

Antibacterial Activity of Clindamycin/BPO in Combination With Adapalene

2024-11-06T20:13:58+00:00

Introduction: Acne guidelines recommend the addition of benzoyl peroxide (BPO) to antibiotics to reduce resistance in Cutibacterium acnes (C. acnes). Pairing the antibiotic/BPO combination with a retinoid, such as adapalene, may further increase treatment efficacy, although research on adapalene’s antibacterial activity is limited. To determine if adapalene improves antimicrobial activity, this in vitro study evaluated minimum inhibitory concentration (MIC) of clindamycin, adapalene, and BPO alone or in combination against both susceptible and resistant C. acnes isolates.

Methods: Part 1a: C. acnes sensitivity to clindamycin, adapalene, or BPO was assessed via MIC values obtained by the broth microdilution method, with lower MIC indicating higher susceptibility. Part 1b: The effect (synergistic, additive, antagonistic, or indifferent [no interaction]) of combining adapalene with clindamycin or BPO on C. acnes inhibition was evaluated using a checkerboard assay, wherein two test compounds are combined in varying concentrations. Part 2: Susceptibility to single formulations of clindamycin, adapalene, and BPO, and fixed-dose combination formulations of an antibiotic (clindamycin or erythromycin) with BPO was determined by measuring antibacterial zone of inhibition using agar diffusion method, with larger diameter indicating increased bacterial inhibition.

Results: Part 1a: Clindamycin demonstrated strain-dependent activity (MIC range: <0.125-64 μg/ml), while BPO and adapalene had no/low activity as indicated by high MIC (>512 and >64, respectively) against the 6 acne-associated strains tested. Part 1b: The combination of adapalene with clindamycin resulted in an additive effect for 3 and no interaction for 1 strain, whereas adapalene with BPO did not result in any interaction against the 4 acne-associated strains tested. Part 2: Activity of single formulations varied, with adapalene 0.1% having no activity (zone of inhibition: 0 cm) against any of the 8 acne-associated C. acnes strains tested. The fixed-dose combination formulations had generally similar activity against all strains tested (range: 0.9-5 cm).

Conclusions: In these in vitro analyses, adapalene and BPO had no/low activity against C. acnes, whereas clindamycin alone or in combination formulations demonstrated strain-dependent activity. The relatively high MIC of BPO is not unexpected and aligns with previous studies in which the in vitro activity of BPO was low compared to its high in vivo antimicrobial activity. Further, addition of the retinoid adapalene had an additive effect on the antimicrobial activity of clindamycin against 3 out of 4 C. acnes strains tested, but no effect on the activity of BPO in vitro. Taken together, these data suggest that when combined with clindamycin/BPO, adapalene may enhance antimicrobial activity, while also bringing its own, unique retinoid mechanism of action to the triple combination, adding to clindamycin's bacteriostatic and anti-inflammatory properties.

Funding: Ortho Dermatologics

Efficacy and Safety of Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel: Post Hoc Analysis by Baseline Disease Severity

2024-11-06T20:31:37+00:00

Introduction: Clindamycin phosphate (CLIN) 1.2%/adapalene (ADAP) 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) is the only triple-combination topical treatment approved for acne. These analyses assessed efficacy and safety of CAB gel by baseline acne severity vs component dyads and branded ADAP/BPO gel.

Methods: These post hoc analyses used data pooled from two phase 2 and two phase 3, double-blind, 12-week studies (NCT03170388, NCT04892706, NCT04214639, NCT04214652). Eligible participants aged ≥9 years (≥12 years in NCT04892706) were randomized to once-daily CAB or vehicle gel. One phase 2 study included dyad combinations of CAB’s active ingredients: ADAP/BPO, CLIN/BPO, and CLIN/ADAP. The other phase 2 study included a head-to-head comparison of CAB gel and branded ADAP 0.3%/BPO 2.5% gel. Efficacy assessments included least-squares mean percent change from baseline in inflammatory/noninflammatory lesions and treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score [EGSS] and clear/almost clear skin). Safety assessments included treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability. Participants were categorized by baseline disease severity: moderate (EGSS = 3; n=1557) or severe (EGSS = 4; n=230).

Results: After 12 weeks, inflammatory lesion reductions in participants with moderate acne were significantly greater with CAB (77.1%) than vehicle (54.1%; P<0.001), the 3 dyads (range, 64.4-69.4%; P≤0.001, all), and branded ADAP/BPO (72.8%; P<0.05). In the severe group, inflammatory lesion reductions with CAB (74.5%) were significantly greater than vehicle (44.4%; P<0.001) and 2 dyads (ADAP/BPO 63.9%, CLIN/BPO 61.3%; P<0.05), and similar to branded ADAP/BPO and CLIN/ADAP (75.4%/73.7%). Reductions in inflammatory lesions were greater than noninflammatory. Over half of CAB-treated participants with moderate disease achieved treatment success at week 12 (53.9% vs 19.5% vehicle; P<0.001), significantly greater than approximately one-third treated with dyads (range, 31.5-35.3%) or branded ADAP/BPO (38.1%; P≤0.001, all). Only CAB and CLIN/ADAP demonstrated significantly greater treatment success rates than vehicle in participants with severe acne at week 12 (30.9% and 34.0% vs 9.0%, respectively, P<0.05). Across all groups, most TEAEs were of mild to moderate severity. Mean cutaneous safety/tolerability scores were ≤1 (1 = mild) across severity groups.

Conclusions: CAB gel demonstrated efficacy and safety in participants with both moderate and severe acne. Acne improvements with CAB were superior to the 3 dyads tested and branded ADAP/BPO in participants with moderate acne and generally numerically greater in participants with severe acne. To our knowledge, these analyses of combination topical acne treatments include data from the only double-blind, vehicle-controlled, head-to-head study to date.

Funding: Ortho Dermatologics.

Environmental Impact and Sustainability Associated with the Practice of Dermatology

2024-10-31T16:45:15+00:00

Purpose: The environmental impact of the practice of medicine including dermatology can be significant, driven by a growing and aging population that increasingly demands medical resources. This review explores the environmental effects of the practice of dermatology and identifies actionable solutions to reduce negative environmental impacts.

Methods: A PubMed search was conducted using the terms (“environmental impact” OR

“sustainability”) AND “dermatology.” Results were screened to include English-only articles between 2018 - 2024 and excluded duplicates. Further exploration of dermatology’s environmental effects was enhanced through citation tracking and additional PubMed searches.

Results: A total of 25 articles were included based on relevance and search terms and an additional 21 were added. Results were categorized into six categories for data representation. Patient travel was the largest contributor to negatively impact the environment, followed by waste management practices, journal publication and written patient material, and traveling to medical conferences. The environmental impact of pharmaceuticals, including topicals, is also notable. Potential sustainable alternatives include teledermatology, more appropriate waste production and segregation, and electronic versus printed formats and more virtual conferences. Additionally, dermatologic disease evolves in response to a changing environment, with new data indicating epidemiological shifts due to climate change. More sustainable practices within dermatology also have the potential to cut total overhead expenses.

Conclusions: Clinical and surgical subspecialties, specifically dermatology, can contribute significantly to environmental pollution, leading to environmental and financial impacts, but implementing simple, documented methods can reduce their ecological footprint and provide potential financial benefits.

Pharmacodynamic effects and exploratory efficacy of afimetoran, a TLR7/8 inhibitor, in patients with cutaneous lupus erythematosus

2024-11-06T21:29:11+00:00

Background: Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin condition occurring alone or as a manifestation of systemic lupus erythematosus (SLE). There is an unmet need for safe and effective CLE-focused treatments. Afimetoran is an investigational, first-in-class, potent oral inhibitor of toll-like receptors (TLRs) 7/8. Given the involvement of TLRs 7/8 in SLE, afimetoran may have therapeutic potential for CLE. A phase 1b randomized, double-blind, placebo-controlled study (NCT04493541) demonstrated preliminary safety and efficacy of afimetoran in patients with active CLE. We assessed the pharmacodynamics, safety, and efficacy of afimetoran and its impact on CLE pathobiology.

Methods: Patients aged 18–65 years with SLE and cutaneous manifestations by EULAR/ACR 2019 classification criteria or biopsy-proven CLE, and modified CLE Disease Area and Severity Index-Activity (CLASI-A) score ≥6, were randomized 2:1 to once-daily afimetoran (30 mg) or placebo for 16 weeks with a 4-week post-treatment follow-up period. The primary endpoints were safety and tolerability; efficacy was exploratory. Transcriptomics and cytokine analyses were performed using peripheral whole blood and serum, respectively, at baseline (pre-dose) and each study visit (weeks 1, 2, 4, 8, 12, 16, and 20 [post-dose]). Statistical analyses compared data from the 13 randomized patients with thirteen age-, ethnicity-, and gender-matched healthy volunteers. Treatment responses were evaluated longitudinally in each treatment arm. The dataset was analyzed using a linear regression model. Gene set variation analysis (GSVA) was performed for pathway enrichment.

Results: 13 patients with CLE were randomized (afimetoran, n=8; placebo, n=5); 12 patients completed 16 weeks of treatment and 1 discontinued after 6 weeks due to COVID-19. Compared with placebo, afimetoran demonstrated a favorable safety profile with no serious adverse events, and showed a greater reduction in CLASI-A scores as early as week 4, which persisted to week 20. Improvement in the molecular disease profile was rapid (week 1), sustained through the 16-week treatment period, and the 4-week post-treatment follow-up period. Expression of interferon (IFN) pathway genes was significantly reduced with afimetoran compared with baseline (ΔGSVA enrichment score [ES]=1.57, P<0.0001) and placebo (ΔGSVA ES=0.56, P<0.01); this effect was maintained through week 16 and ≥4 weeks post-treatment. Expression of TLR7 and TLR8 pathway genes and key cytokines (interleukin [IL]-6, tumor necrosis factor α, IL-18, IFNγ, macrophage inflammatory protein-1 alpha [CCL3/MiP1α] or beta [CCL4/MiP1β]) were greatly reduced with afimetoran treatment. GSVA demonstrated robust pharmacodynamic activity on immune cell populations, including immature and activated dendritic cells, macrophages, and inflammatory pathway signatures.

Conclusion: In patients with CLE, afimetoran was safe, well tolerated, and demonstrated durable efficacy beyond the treatment period. Afimetoran’s clinical effects and potent pharmacodynamic impact on the molecular disease profile suggest a substantial therapeutic benefit for patients with CLE.

Efficacy and Safety of Ruxolitinib Cream for the Treatment of Moderate to Severe Chronic Hand Eczema: Top-Line Results From a 16-Week, Multicenter, Randomized, Double-Blind Study

2024-11-07T00:52:31+00:00

Hand eczema is a common inflammatory disorder involving skin of the hands. Chronic hand eczema (CHE) is defined as hand eczema that persists for >3 months or recurs ≥2 times within a 12-month period. The efficacy and safety of ruxolitinib (selective Janus kinase [JAK] 1/JAK2 inhibitor) cream was investigated in adults with moderate to severe CHE in a phase 2, randomized, double-blind, vehicle-controlled study (NCT05906628). Patients aged ≥18 years with a diagnosis of CHE for ≥6 months, an Investigator’s Global Assessment (IGA)-CHE score of 3 or 4, and no current or history (≤5 y) of atopic dermatitis were randomized 1:1 to apply twice-daily 1.5% ruxolitinib cream or vehicle cream for 16 weeks of double-blind treatment. Patients (N=186) had a median (range) age of 50.0 (18–80) years, and 59.7% were female. The median (range) Itch numerical rating scale (NRS) score was 6.6 (2.1–10), and 72.6% of patients had an IGA-CHE score of 3. At Week 16, significantly more patients who applied ruxolitinib cream versus vehicle achieved IGA-CHE treatment success (primary endpoint; 53.2% vs 10.9%; P<0.0001), defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline. Significantly more patients who applied ruxolitinib cream versus vehicle achieved a ≥4-point improvement from baseline in Itch NRS score (Itch NRS4) at Week 4 (46.7% vs 17.6%; P<0.0001; key secondary endpoint) and Week 16 (52.2% vs 23.1%; P<0.0001; key secondary endpoint). Numerical improvements in Itch NRS4 with ruxolitinib cream versus vehicle were observed at Day 2 with statistically significant improvement observed on Day 7 (27.4% vs 9.0%; P=0.0024; key secondary endpoint). Substantially more patients who applied ruxolitinib cream versus vehicle achieved a ≥75% or ≥90% improvement from baseline in Hand Eczema Severity Index (HECSI) score at Week 16 (80.2% vs 26.9% and 64.0% vs 11.5%, respectively). Ruxolitinib cream was generally well tolerated through Week 16 with no new safety signals; no serious infections, major adverse cardiovascular events, malignancies, or thromboses were observed. Application site reactions were infrequent. No treatment-related grade ≥3 treatment-emergent adverse events (TEAEs) were reported, and no patients discontinued owing to a TEAE. In conclusion, ruxolitinib cream demonstrated significant reductions of CHE signs and symptoms versus vehicle through Week 16 and was generally well tolerated, consistent with the known safety profile. (Funding, Incyte Corporation)

Worldwide Clinical and Real-World Exposure to Baricitinib

2024-11-08T15:40:15+00:00

Introduction: Baricitinib (BARI), an oral selective JAK inhibitor, is approved in many geographies for adults with rheumatoid arthritis or alopecia areata and for patients as young as age 2 years with atopic dermatitis or juvenile idiopathic arthritis. It is also approved in the US for hospitalized patients with COVID-19 infection. We report the worldwide clinical trial and real-world exposure to BARI across a range of diseases, ages and racial backgrounds.

Methods: Real-world patient exposure estimates were calculated based on total mg sold, average daily dose, and average length of therapy as reported to regulatory agencies through the cumulative timeframe ending Jan. 31, 2024. Clinical trial exposures were based on actual exposures from completed trials through Feb. 13, 2024, and estimates were made for ongoing blinded trials based on the enrolment/randomization schemes

Results: In the real-world setting, an estimated 1,836,600 patients have been exposed to the following BARI doses: 1 mg, ~2,000 (0.1%); 2 mg, ~524,900 (28.6%); 4 mg, ~1,309,600 (71.3%). Of these estimated exposures, ~ 57% were for COVID-19 with the remaining for all other indications combined. Across 59 clinical trials (completed and ongoing), an estimated 14,660 subjects (548 healthy volunteers and 14,112 patients) have received BARI since June 2008. Exposures from completed studies include 10,276 patients (62% female), 399 of whom were <18 yrs of age (≤1 month, N=4; 1 month - ≤2 yrs, N=24; >2 - ≤12 yrs, N=111; >12 - ≤18 yrs, N=260), 8820 were >18 to ≤65 yrs, 1027 were >65 yrs, and 30 had age unknown. An additional 467 adolescent and pediatric patients down to the age of 2 have been treated with BARI for atopic dermatitis in an ongoing clinical trial, bringing the total number of patients <18 years of age to 866 across dermatologic, rheumatologic, other autoimmunologic, and acute infectious diseases (excluding alopecia areata for which there is an ongoing pediatric trial). Clinical trial exposures by racial and ethnic background are as follows: Asian, N=2,491; Black, N=450; Caucasian, N=6,237; other, N=496; multiple, N=135; unknown, N=467.

Conclusion: There has been extensive real-world exposure to BARI across indications and populations, and BARI is a well-studied molecule in clinical trials, across varied disease states, racial populations and ages. Since average daily dose and length of therapy may vary over time, real-world exposures are only an estimate of total patients receiving BARI. Exposures in clinical trials include patients as young as less than 1 month of age up to patients over the age of 65 years. While these exposures do not indicate efficacy or safety, they provide data to establish the overall profile of the drug and can inform on its performance over time across a variety of populations.

Targeted 308-nm Excimer Laser A Safe and Effective Solution for Inflammatory Skin Disorders

2024-10-31T17:28:51+00:00

Background: The 308-nanometer excimer laser is a targeted ultraviolet B (UVB) light therapy that delivers high-intensity UVB rays directly to affected skin. It has shown considerable efficacy in managing various inflammatory skin conditions, including Psoriasis, Vitiligo, Atopic dermatitis (Eczema), Leukoderma, Alopecia Areata, Chronic recalcitrant dermatitis, Lichen planus, Cutaneous T-cell Lymphoma (e.g. Mycosis fungoides/ Sezary Syndrome), Parapsoriasis, Pityriasis lichenoides chronica, Pruritus, Urticaria pigmentosa, Superficial mycoses (e.g., dermatophytosis [ringworm]. The patient demographic of some of these conditions (e.g. Vitiligo) tends to skew towards patients with darker skin tones.

Results: The excimer laser is particularly effective for treating resistant areas, such as the scalp, palmoplantar psoriasis, and hand and foot dermatitis, which often do not respond well to conventional therapies.

It has also demonstrated notable success in promoting repigmentation in facial vitiligo, especially in patients with Fitzpatrick skin types IV–VI.

Treatment results are typically observed quickly after 5-10 sessions, with sustained improvement and psoriasis clearance evident even at 1-year follow-up.

Over the years, access to the Excimer laser procedures has expanded with the availability of these procedures in many private clinics as well as academic facilities. That has increased the availability of the treatment modality and patient choice of therapy.

Conclusions: The excimer laser provides a safe, non-invasive treatment option with a strong record of efficacy for multiple inflammatory skin conditions. It is a viable alternative to systemic therapies and can be used either alone or in conjunction with other treatments for optimal patient outcomes.

How Automation in Electronic Medical Records Can Lead to Errors in Dermatology

2024-07-29T20:33:05+00:00

The integration of electronic health records has revolutionized healthcare by facilitating communication among providers, but it has also introduced significant challenges. In dermatology, a particular issue arises with the use of electronic medical record (EMR) systems that employ auto-populated fields on digital pathology requisition forms (RFs) for skin biopsies. These systems allow for the rapid selection of pre-set descriptions and differential diagnoses, which, while timesaving, frequently lead to diagnostic inaccuracies and potentially detrimental impacts on patient care.

Dermatopathologists often receive biopsy specimens with RFs that list multiple provisional diagnoses based on generic, EMR-generated descriptions, which may not accurately represent the patient’s condition. This practice hampers the ability of dermatopathologists to perform effective clinicopathologic correlation, crucial for accurate diagnosis. We highlight that the convenience of EMR systems can discourage clinicians from recording detailed, accurate clinical observations. Consequently, this lack of detailed documentation prevents dermatopathologists from making informed diagnoses by correlating histologic features with clinical appearances. The current practice of using EMRs without consideration for their clinical relevance not only wastes healthcare resources but also poses a significant medico-legal risk. Therefore, refining EMR practices and integrating more comprehensive clinical data will ensure greater accuracy in dermatological diagnoses.

Effects of Mineral and Almond Oil Administration on Transepidermal Water Loss and Skin Acidity in Chronic Renal Failure Patients Undergoing Hemodialysis

2024-10-14T17:50:58+00:00

Introduction: Patients undergoing hemodialysis experience decreased moisture content in the dermis due to fluid transfer during the dialysis process, causing xerosis, pruritus, and damage to the skin barrier. Almond oil and mineral oil are well-known moisturizers used in skin care products.

Objectives: To compare the effect of almond oil with mineral oil on transepidermal water loss (TEWL) and skin acidity in hemodialyzed chronic renal failure (CRF) patients.

Methods: An experimental study was conducted on patients with chronic renal failure (CRF) undergoing hemodialysis at Dr. Moewardi Hospital in Indonesia. The study involved applying mineral and almond oils twice daily on the right and left forearms for four weeks. We measured TEWL and pH levels before and after the treatment.

Results: There is a significant difference in TEWL between before and after mineral oil application (p=0.036), but not in the almond oil arm (p=0.394). Subsequently, the change of TEWL value significantly differed between mineral oil and almond oil (p=0.043). However, the effects of mineral oil and almond oil on pH were insignificant (p=0.574 and 0.268, respectively).

Conclusion: After undergoing hemodialysis, CRF patients experienced a statistically significant reduction in transepidermal water loss (TEWL) when using mineral oil compared to both baseline and almond oil.

A Case of Cutaneous Squamous Cell Carcinoma Treated with Neoadjuvant Cemiplimab

2024-08-31T20:14:05+00:00

We present a case describing the successful treatment of a 68-year-old male with high-risk cutaneous squamous cell carcinoma (cSCC) using neoadjuvant cemiplimab. The patient presented with a rapidly growing papule on the left hand, which was initially treated with wide local excision and subsequently developed axillary lymphadenopathy. After radiation therapy led to complications, the patient received four cycles of cemiplimab, resulting in significant tumor necrosis and minimal residual disease. This case underscores the potential of cemiplimab as a neoadjuvant therapy for cSCC, offering an effective treatment with fewer adverse effects compared to traditional therapies. The report highlights the importance of a multidisciplinary approach in optimizing outcomes for patients with advanced cSCC.

Eosinophil-rich Linear IgA Bullous Dermatosis: A Case Report of a Rare Entity

2024-08-31T20:15:43+00:00

Linear IgA bullous dermatosis (LABD) is an uncommon autoimmune bullous disease characterized by a subepidermal neutrophilic infiltrate. It classically presents as widespread tense vesicles in an annular pattern and is defined by the presence of linear deposition of IgA at the dermal-epidermal junction. Eosinophil-rich LABD has been rarely reported in the literature, including in association with COVID-19 booster vaccination, parvovirus B19 infection, hematologic malignancies, and drug-induced LABD. The varied clinical and histopathologic findings often make it difficult to differentiate LABD from other blistering diseases such as bullous pemphigoid and dermatitis herpetiformis. For this reason, immunofluorescence and serologic testing are critical for identifying the underlying diagnosis.

Palmoplantar Psoriasis Treatment with Topical Roflumilast 0.3%

2024-10-09T16:31:16+00:00

Palmoplantar psoriasis is a manifestation of psoriasis that includes pustules, scales, and erythematous hyperkeratotic plaques on the palms of the hands and the soles of the feet. Despite being limited to these regions, palmoplantar psoriasis is difficult to treat and imposes a greater level of quality-of-life burden compared to plaque psoriasis. We describe a case of palmoplantar psoriasis refractory topical corticosteroid and dupilumab that was successfully treated with topical roflumilast 0.3% once daily.

Successful Treatment of Perioral Dermatitis with Upadacitinib

2024-10-31T14:44:21+00:00

Perioral dermatitis (POD) is a benign, chronic inflammatory skin condition characterized by small papules, pustules, and erythematous scaly patches around the perioral region. Treatment is not reliably effective, and the condition can be prolonged. We herein report a case of the successful treatment of perioral dermatitis (POD) using upadacitinib. A 45-year-old female with a history of rosacea, presented to the clinic with a 2-3-year history of severely pruritic erythematous papules around the chin and mouth, consistent with POD. Our study demonstrates that Janus kinase inhibitors are a promising therapeutic modality for this condition.

Pityriasis Rubra Pilaris, Refractory to IL-17A Inhibition, with Rapid Improvement Following IL-17A/IL-17F Blockade by Bimekizumab

2024-10-01T18:36:49+00:00

Introduction: Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder which can severely affect patient quality of life. While there are no FDA-approved therapies for PRP, methotrexate and acitretin are often used as first line treatments. Recent analyses have implicated dysregulation of the IL23/IL17 axis in PRP pathogenesis and the use of biologics for severe cases have been reported in the literature.

Case Report: We report the case of a male in his thirties who presented with PRP refractory to a second course of secukinumab. Physical exam revealed diffuse salmon-colored hyperkeratotic patches coalescing to cover his entire body (BSA >95%). The patient was started on combination therapy with acitretin and bimekizumab. The patient recovered rapidly, with near total resolution of his skin findings four weeks after beginning treatment.

Discussion: Unlike earlier biologics targeting IL-17, bimekizumab has activity on IL-17F in addition to IL-17AF and IL-17A. The efficacy of bimekizumab in this case may signify an important role for IL-17F in PRP pathogenesis. Bimekizumab may offer improved efficacy for the treatment of pityriasis rubra pilaris (PRP) in patients who do not respond to other therapies.

Multiple Injection Site Reactions after Treatment with Different Biologics for Psoriasis and Psoriatic Arthritis

2024-09-28T13:51:57+00:00

Psoriasis (PsO) is an autoimmune disease characterized by erythematous, pruritic, and scaly plaques that can be distributed throughout the body. The development of biologic treatments targeting an array of molecular pathways, including tumor necrosis factor-ɑ or interleukins (IL) 12, 23, 17A, and 17F, has advanced treatment options for these patients. In this article, we report a unique case of a 35-year-old female with 11-year history of PsO and a new onset of guttate PsO following an episode of streptococcal pharyngitis. She was subsequently treated with guselkumab, bimzekizumab, and ixekizumab, developing injection site reactions to each biologic. The patient was suspected to be allergic to polysorbate-80 (PS-80), an aqueous medium to stabilize biologics before administration. Notably, the patient had a negative response to PS-80 on allergy testing, and it remains unclear why the patient experienced ISR with certain medications and not others. Further research is needed to characterize ISR across the different biologics, particularly newer medications being utilized in clinical settings.

The Treatment of Lichen Sclerosus with Topical Roflumilast 0.3% Case Study

2024-09-01T20:17:12+00:00

Lichen Sclerosus is a chronic inflammatory skin disease predominantly affecting post-menopausal women. Currently, the first line treatment approach for lichen sclerosus is ultra potent topical corticosteroids for 12 weeks. A treatment challenge to this approach is the risk of steroid atrophy due to the use of potent topical steroids on the genital skin. We describe reduction of erythema and symptomatic improvement following treatment with topical roflumilast 0.3% once daily in a patient with lichen sclerosus who refused topical corticosteroids.

Sclerotic Fibroma in a Patient with Birt-Hogg-Dubé Syndrome

2024-06-20T00:04:52+00:00

Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disorder characterized by cutaneous lesions and systemic findings such as renal neoplasms, pulmonary cysts, and spontaneous pneumothoraces. Fibrofolliculomas, trichodiscomas, and acrochordons are the most common cutaneous lesions associated with BHD. Some cases with mucocutaneous lesions have also been reported. We report a sclerotic fibroma that developed over a previous thoracotomy scar of a patient with BHD.

Concomitant Eruptive Squamous Atypia and Bullous Drug Eruption Associated with Pembrolizumab

2024-08-31T22:42:11+00:00

This study involves the case of a rare eruptive squamous atypia (ESA) reaction and concurrent bullous eruption following pembrolizumab treatment for recurrent neck squamous cell carcinoma. This report aims to raise awareness to possible concurrent skin reactions related to PD-1 inhibitor treatment that has otherwise only been reported twice in melanoma patients.

The Non-Healing Wound: An Early Clue to Calciphylaxis

2024-09-08T22:25:39+00:00

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare disease that presents as painful, necrotic lesions. While calciphylaxis is most commonly associated with renal insufficiency, calciphylaxis can occur in those without renal impairment. A case of non-uremic calciphylaxis occurring at a below-knee amputation site presenting as a single non-healing wound is provided; this presentation stands in stark contrast to the multiple, exquisitely painful lesions that are typical of calciphylaxis.

A Case of Zoonotic Domestically Acquired Hansen Disease (Leprosy) in the State of Georgia

2024-08-03T23:21:10+00:00

Introduction: Hansen Disease (HD) is an infection of the bacteria Mycobacterium leprae causing rash and anesthesia of the skin. It is endemic to many developing countries, where it is spread by direct contact. Zoonotic transmission through the 9-banded armadillo (Dasypus novemcinctus) has been documented in North America. HD is rare in the state of Georgia and most cases are from individuals travelling from HD endemic regions.

Case Report: The patient developed red, infiltrated, anesthetic plaques covering 20% of her body. Fite staining revealed mycobacterial organisms suggesting lepromatous HD. The patient had no relevant history of travel or personal health history. The patient gardened outdoors in Southern Georgia. She knew armadillos were present in the area, but she did not have direct contact with one. The suspected mode of transmission was through feces of an infected armadillo in the soil. The patient is being treated with a 2-year course of rifampin, clofazimine, and dapsone, and reports improvement.

Discussion: Domestically acquired HD is generally seen in other Southern states with greater armadillo populations. The range of the 9-banded armadillo is expanding, which potentially puts a greater area of the country at risk for exposure to HD. Therefore, increasing resources for treatment of HD is important.

Conclusion: This case report presents a case of HD with indirect zoonotic transmission.

Utilizing Upadacitinib for the Management of Hailey-Hailey Disease

2024-10-31T14:41:32+00:00

Hailey-Hailey Disease (HHD) is a rare disease associated with mutation of the ATP2C1 gene characterized by skin blistering and erosion. Here, we report a case of a patient with HHD who significantly improved after treatment with upadacitinib. A 55-year-old male with biopsy-confirmed Hailey-Hailey disease presented with a 20-year history of ill-defined, brightly erythematous, painful patches initially on the neck and subsequently involving the penile shaft. Following treatment with 30mg of upadacitinib, the patients neck ulcers gradually re-epithelized. This case adds to the growing body of literature supporting the use of Janus kinase inhibitors as a therapeutic modality for this condition.

Carpal Tunnel Corticosteroid Injection Treatment of Nail Lichen Planus

2024-09-01T19:08:34+00:00

Treatment for nail lichen planus (NLP) typically involves the use of intralesional or systemic corticosteroids. However, both modalities have distinct considerations. Systemic options are typically reserved for severe cases due to potential adverse effects while intralesional injections are limited due to patient discomfort. Here we present a case in which a corticosteroid injection for carpal tunnel syndrome led to incidental bilateral improvement in a patient’s nail lichen planus. Carpal tunnel injection may be an alternative to more traditional treatments and is a potential area for further research.

Photosensitivity Dermatitis associated with the Moderna Booster Vaccination

2024-11-16T16:07:04+00:00

Adverse reactions have been documented following administration of mRNA COVID vaccinations, including systemic and local cutaneous reactions. Cutaneous reactions have been reported more frequently and of greater severity when vaccinated with the Moderna vaccine compared to the Pfizer/BioNTech vaccine. While multiple studies have investigated cutaneous reactions following initial vaccinations, few have reported on the effects of booster vaccinations, specifically in individuals of darker skin color. Additionally, we have found no reported cases of photosensitive dermatitis following vaccination. Thus, we present a case of photosensitivity dermatitis likely secondary to a booster shot of the Moderna vaccination in a Fitzpatrick Type IV 81-year-old female patient.

Allergens Causing Allergic Contact Dermatitis in Cosmetic Products: A Systematic Review

2024-06-29T18:26:20+00:00

Background: The increasing use of cosmetics worldwide has led to a rise in allergic reactions, particularly due to inadequate risk assessment. Identifying common allergens in cosmetic products causing dermatitis is crucial for effective prevention and management strategies.

Objectives: This systematic review aims to determine the list of allergens that most commonly cause allergic contact dermatitis in cosmetic products and to find the patch test positivity rate for cosmetic products. Methods: This systematic review, following the PRISMA guidelines, investigated patch test results on cosmetic-induced contact dermatitis from January 2013 to September 2023 on PubMed, Cochrane, and Medline databases. Inclusion criteria comprised retrospective cohort and clinical trial studies reporting patch test positivity rates and positive allergens in cosmetics, with eligibility determined through independent screening, full-text evaluation, and data extraction. Exclusion criteria comprised abstract-only publications, non-English or Indonesian languages, review articles, and studies with incomplete text.

Result: 13 studies were included out of 2,162 initially screened articles, involving 111,097 participants. The selected studies encompassed ten retrospective studies and three clinical trials conducted in various locations, including India, Brazil, North America, Korea, Sweden, and the Czech Republic. The patch test positivity rate ranged from 13% to 100%. The predominant allergens identified in cosmetics were nickel sulfate, fragrance mix I, cobalt chloride, para-phenylenediamine base, potassium dichromate, and balsam of Peru.

Conclusion: This systematic review highlights the diversity in patch test positivity rates and identifies key allergens responsible for allergic contact dermatitis in cosmetic products, emphasizing the need for comprehensive evaluation and awareness of cosmetic safety.

A Systematic Review of the Association of Elastosis Perforans Serpiginosa and Congenital Disorders

2024-10-28T23:06:34+00:00

Background: Elastosis perforans serpiginosa (EPS) is a skin condition marked by transepidermal elimination of abnormal elastic fibers, with a classical presentation of papules or plaques arranged in serpiginous, annular, or arcuate patterns on the neck, face, arms, or other flexural regions. A previous review of the literature reported that approximately 1/4 of EPS cases are associated with congenital disorders, including Down syndrome, Ehlers-Danlos syndrome, Marfan syndrome, osteogenesis imperfecta, and pseudoxanthoma elasticum. To the knowledge of these authors, no review examining the association of EPS and congenital disorders has been performed since 1968.

Objective: The primary objective of this paper is to perform an updated review of the literature focused on the associations between EPS and congenital disorders.

Methods: We searched electronic databases (Medline, Web of Science, PubMed) for literature pertaining to EPS and Down syndrome, Ehlers-Danlos syndrome, Marfan syndrome, osteogenesis imperfecta, and pseudoxanthoma elasticum.

Results: Evidence for the association of EPS and congenital disorders is 57 cases from 48 published papers.

Conclusions: Our results suggest an association between EPS and congenital disorders. However, current evidence is limited to case reports, underscoring the need for future research investigating the relationship between EPS and congenital disorders.

Tissue-Engineered Skin Substitutes for Use in Clinical Dermatological Practice

2024-09-03T20:07:14+00:00

Skin replacements are essential in dermatology as they serve to connect the gap between conventional wound care and surgical procedures. Due to pioneering innovations from the last century, tissue-engineered skin substitutes have significantly advanced in the field of dermatology, offering new hope for patients with complex wound healing needs. Whilst before, skin grafting was performed to act as an intermediary to promote skin healing, it has now evolved to also mimic skin structure and function. To our knowledge, there have not been any summaries on the use of tissue-engineered in dermatology. Therefore, we conducted a scoping review to summarize research papers which performed human clinical trials and follow-up work using synthetic lab-made skin with a clear clinical application from the last 30 years.

Imposter Syndrome in Dermatology

2024-09-02T21:24:24+00:00

Background: Dermatology residents may doubt their ability to become effective dermatologists. This study explores the prevalence of imposter syndrome (IS) within dermatology. Prior research in other specialties indicates that residents perceive themselves as less competent and experience higher rates of IS compared to faculty. Additionally, IS has been reported to be more common among female trainees.

Purpose: This study sought to identify imposter syndrome in the field of dermatology and at which point in their career dermatologists feel qualified. We hope that this information can inform residency training.

Methods: This cross-sectional study distributed a 12-question survey to the Association of Professors of Dermatology (APD) listserv.

Results: The survey received 264 responses. Of the respondents, 81.9% reported that they did not feel comfortable calling themselves a dermatologist until after their third year of residency. We found no significant differences in imposter syndrome based on gender or work experience in dermatology prior to residency. Current career level of respondents was a significant determinant of response. Lack of unsupervised practice prior to residency completion was the most commonly cited reason for imposter syndrome (81.2%).

Conclusions: The majority of dermatologists do not consider themselves a dermatologist until completion of residency, likely due to a lack of unsupervised practice. Providing residents with experiences to simulate unsupervised practice may reduce the prevalence of imposter syndrome.

Publication Outcomes of Abstracts Presented at the 2020 Society for Investigative Dermatology Annual Meeting

2024-11-11T21:00:35+00:00

The Society for Investigative Dermatology (SID) was created to promote the advancement of skin biology research. The organization hosts a conference annually that allows for the dissemination of basic science knowledge to advance dermatology research to new heights. Our study investigates the publication status of research abstracts presented at SID to determine if publication rates were similar to those of other widely attended conferences in dermatology. We performed a literature search for each abstract presented at the conference in 2020 and found that only 27.6% of abstracts make it to publication. Due to various reasons outlined in this article, publication rates of SID projects are lower than many other dermatology conferences attended. Therefore, conference participants should be aware of how study designs and research topics can influence publication outcomes.

Investigating the Impact of Financial Sponsorship in Dermatology Research

2024-09-02T21:19:57+00:00

Introduction: Financial sponsorship plays a crucial role in advancing dermatologic research, yet its impact on research quality and visibility is not well-defined. This study aims to evaluate the association between financial sponsorship and the quality of evidence, publication impact, and research collaboration in dermatology.

Methods: We analyzed 1,380 dermatology articles published from October 2013 to October 2023 in three leading journals. Data collection was conducted using REDCap. We assessed the proportion of sponsored studies and their impact in terms of citation frequency, author count, and journal impact factors. Statistical analyses were performed using t-tests, chi-squared tests, and regression analysis in STATA VSN 16.1.

Results: Sponsored articles comprised 48.2% of the total, with the National Institutes of Health (NIH) being the predominant funder. These articles showed significantly higher citation rates and more authors per article compared to non-sponsored ones. The mean journal impact factor was also higher for sponsored studies. Furthermore, sponsored studies were more likely to employ prospective study designs, indicative of higher evidence quality.

Discussion: Financial sponsorship significantly enhances the visibility and quality of evidence in dermatologic research. The findings underscore the need for increased advocacy for funding, particularly in clinical research within dermatology, to foster greater research collaborations and more impactful scientific discoveries.

Cutaneous Manifestations of the Hemiscorpius lepturus Stings

2024-09-01T23:52:04+00:00

The Penile Lymphatic Malformation Causing Urinary Obstruction

2024-09-02T20:58:47+00:00

Pediatric Viscerocutaneous Loxoscelism: A Web of Clinical Challenges

2024-08-10T19:46:37+00:00

Differentiating between Central Centrifugal Cicatricial Alopecia, Traction Alopecia, and Alopecia Areata in Black Patients: Photographic Examples from a Clinical Trial

2024-11-08T15:49:36+00:00

Introduction. Following the initial BRAVE-AA1 clinical trial, a study addendum was added in which Black patients with severe alopecia areata (AA) were entered into open label treatment with baricitinib 4 mg for 52 weeks. Photographs were taken at screening to confirm eligibility and were reviewed by a central expert reviewer. These photographs provide an opportunity to examine diagnostic challenges in AA, in Black patients, especially women.

Methods. In the BRAVE-AA1 addendum 5 study, photographs of five planes of the scalp (left, right, posterior, frontal, and top of head) were obtained at screening and post-baseline. Camera equipment and a study-specific photography manual was provided to all sites, personnel were trained to conduct photography under similar lighting conditions and magnifications. Images were taken with polarization and cross-polarization lenses and reviewed for compliance with standardization procedures. At screening, all images were reviewed centrally by the external reviewer to determine consistency with AA. For this disclosure, images of both AA and non-AA cases were selected by the authors to illustrate key signs that can aid in differentiating AA, from the other alopecias that were observed in the screened patient population.

Results. Of the 36 patients with photographs reviewed by the central expert reviewer, 12 (33%) were diagnosed with CCCA or other scarring alopecia; 11 of these patients were female. Based on photography review, presentations involving the vertex, midscalp and parietal scalp, with sparing of the occipital scalp was suggestive of CCCA. The presence of scalp hypopigmentation and hyperpigmentation reflected the inflammatory processes and scarring associated with CCCA. The presence of “fringe sign” suggested traction alopecia; while AA was characterized by the presence of asymmetrically distributed, circular smooth bald patches. The photographic images portrayed the complexities of hair loss patterns that can occur within a single patient, and some patients had co-occurrence of more than one pattern of alopecia. Scalp biopsies were not performed which is limitation of these data.

Conclusions. Misdiagnosis of AA can occur in some patient populations with other forms of hair loss that mimic the disease. More than one type of hair loss can co-occur in a single patient, thereby limiting the maximal potential improvement a patient may experience with treatment. While photographic evidence alone may not conclusively determine the diagnosis, the present disclosure provides visual examples of helpful signs that can assist dermatologists to diagnose and to support an appropriately tailored treatment plan.

Distribution of SALT Scores with Ritlecitinib Treatment up to 24 months from the ALLEGRO Phase 2b/3 and Long-Term Phase 3 Clinical Studies in Alopecia Areata

2024-11-07T21:11:59+00:00

Background:
• Alopecia areata (AA) is an autoimmune disease that has an underlying immuno-inflammatory
pathogenesis and is characterized by non-scarring hair loss ranging from small patches to complete
scalp, face, and/or body hair loss1
• Ritlecitinib, an oral JAK3/TEC family kinase inhibitor, demonstrated efficacy and safety up to 48 weeks in
patients aged ≥12 years with AA in the ALLEGRO phase 2b/3 study (NCT03732807; “ALLEGRO-2b/3”)2
• The long-term efficacy of ritlecitinib in patients who rolled over from ALLEGRO-2b/3 to the ongoing
phase 3, open-label ALLEGRO-LT study (NCT04006457) has been reported in terms of the proportions of
patients with Severity of Alopecia Tool (SALT) scores of ≤20 and ≤10 (≤20% or ≤10% scalp without hair)
at Month 243
• However, the distribution of SALT scores in the overall population, including patients not reaching the
SALT score ≤20 and ≤10 thresholds, has not yet been described
OBJECTIVE
• This study describes changes in the distribution of SALT scores over 24 months of ritlecitinib treatment
in the overall population and in age and disease severity subgroups

Methods:
Study design and patients
• Key inclusion criteria in ALLEGRO-2b/3:
- Age ≥12 years
- Diagnosis of AA with ≥50% scalp hair loss due to AA (including alopecia totalis [AT] and alopecia universalis [AU])
- Maximum duration of current episode of hair loss ≤10 years
• This analysis includes patients who received ritlecitinib 50 mg once daily (QD) without a loading dose in
ALLEGRO-2b/3 and who subsequently rolled over into ALLEGRO-LT where they continued to receive
ritlecitinib 50 mg QD (Figure 1)
- Continuation criteria for adolescents (aged 12-17 years) in ALLEGRO-LT: ≥50% improvement from baseline in SALT score
by Month 3 for rollover patients from ALLEGRO-2b/3 and SALT score ≤20 by Month 6 in ALLEGRO-LT
Figure 1. Study design and patient population
Combined
ritlecitinib
50 mg group
(N=191)
ALLEGRO phase 2b/3 ALLEGRO-LT
Loading
(4 weeks)
Maintenance
(20 weeks)
Extension
(24 weeks)
Long-term study
(60 months)
Group A (n=131) 200 mg 50 mg 50 mg 50 mg
Group B (n=129) 200 mg 30 mg 30 mg 50 mg
Group C (n=130) 50 mg 50 mg 50 mg 50 mg
Group D (n=132) 30 mg 30 mg 30 mg 50 mg
Group E (n=61) 10 mg 10 mg 10 mg 50 mg
Group F (n=63) Placebo Placebo 200 mg 50 mg 50 mg
Group G* (n=61) Placebo Placebo 50 mg 50 mg
De novo group (n=447) 200 mg 50 mg
*Data while on placebo were not included in this analysis; data from patients in Groub G were rebaselined from the start of treatment with ritlecitinib.
Assessments and statistical analysis
• The distribution of patients according to SALT score (as observed) was assessed through Month 24 for
the overall population and subgroups based on age (adults [≥18 years] vs adolescents [12-17 years]) and
disease severity (patients with AT/AU vs those without AT/AU)
• The data cutoff date was December 9, 2022

Results:

The analysis included 191 patients (27 adolescents and 164 adults) (Table 1)
• At the time of data cutoff, 71 patients had discontinued; withdrawal by
patient (n=19), adverse events (n=18), and lack of efficacy (n=14) were the
most common reasons for discontinuation
• The distribution of participants by SALT score (as observed) at baseline, Month
12, and Month 24 are presented for the overall population (Figure 2)
(Interactive dynamic plot)
• Per the inclusion criteria, all participants had a SALT score of ≥50 at baseline;
136/191 patients (71.2%) had SALT >90
• Among patients who had a nonmissing SALT score, 56/178 (31.5%), 37/164
(22.6%), and 17/120 (14.2%) were in the SALT >90-100 category at Months 6,
12, and 24, respectively
• Reductions in the number of patients in the other SALT >50 categories were
observed from baseline through Month 24
• At Month 12, 56/164 (34.2%) and 18/164 (11.0%) patients were in the SALT
0-10 and >10-20 categories, respectively, with 61/120 (50.8%) and 12/120
(10.0%) patients in these categories at Month 24
• Among the patients with AT/AU at baseline, 18/69 (26.1%) and 6/69 (8.7%)
were in the SALT 0-10 and >10-20 categories, respectively, at Month 12; 25/47
(53.2%) and 3/47 (6.4%) were in these categories, respectively, at Month 24
(Figure 3) (Interactive dynamic plot)
• For the adolescent participants, 10/22 (45.5%) and 4/22 (18.2%) were in the
SALT 0-10 and >10-20 categories, respectively, at Month 12, and 11/14
(78.6%) and 0/14 (0%) were in these categories at Month 24 (Figure 4)

Conclusions:
• Over 24 months, daily treatment with ritlecitinib 50 mg resulted in fewer patients in
the highest SALT score categories
• These data provide a comprehensive overview of patient response to ritlecitinib
treatment and enable us to understand treatment response and time frames while
on treatment with ritlecitinib

• This information can empower clinicians when counseling patients and managing
treatment expectations based on patient characteristics
• This study also shows that response to treatment improves over time, which
suggests that adequate time should be given when assessing treatment efficacy

Characterizing Lipid Changes and Use of Lipid-Lowering Medications in Patients With Alopecia Areata Treated With Baricitinib: Integrated Results From the BRAVE-AA1 and -AA2 Clinical Trials

2024-11-08T15:26:05+00:00

Introduction. Elevations in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) can occur with baricitinib treatment, consistent with a class effect of JAK inhibitors. In this analysis, we characterized changes in lipid levels and use of lipid-lowering medication among patients with severe alopecia areata (AA) treated with baricitinib through 152-weeks of treatment.

Methods. Two integrated datasets from the BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) trials were analyzed: 1. Extended BARI AA includes patients treated with continuous baricitinib 2 mg (N=383) and 4 mg (N=565) from baseline and censored at dose change: 2. ALL BARI AA (N=1303) includes data for patients who received ≥1 dose of baricitinib at any time. Outcomes included abnormal changes in lipid parameters, mean change from baseline in lipids, and concomitant use of lipid-lowering medications.

Results. At time of enrollment, 43% of patients had hypercholesterolemia. Incidence rates for categorical increases in total cholesterol (TC; ≥240mg/dL), LDL-C (≥130 mg/dL), and HDL-C (>60 mg/dL) were 11.8, 13.3, and 12.9 per 100 patients-years of exposure, respectively in the ALL BARI AA dataset. In the Extended BARI AA the mean maximal increase in lipids (mg/dL) for baricitinib 4 mg was 20.9 for TC, 12.4 for LDL-C, and 8.5 for HDL-C. Changes occurred early and stabilized by one year for TC and LDL-C and by 12 weeks for HDL-C. 6.1% (n=79) of patients in the ALL BARI AA dataset used lipid-lowering medication at baseline; post-baseline, 3.9% (n=51) discontinued this medication and 4.7% (n=61) initiated lipid lowering medication. No patients discontinued baricitinib treatment due to treatment-emergent adverse events related to hyperlipidemia.

Conclusions. Elevations in TC, LDL-C, and HDL-C, but not triglycerides were associated with baricitinib treatment in patients with AA, consistent with a class effect of JAK inhibitors. The relatively low use of lipid-lowering medications at baseline despite the prevalence of hypercholesterolemia may reflect undermanagement of this condition in the population. Notably, the mean maximal magnitude of increase in lipid levels on baricitinib was modest. Initiation of lipid-lowering medication was infrequent, and no patients discontinued due to lipid abnormalities.

Patient Profile and Treatment Characteristics of Early Ritlecitinib Initiators in the US

2024-11-08T16:32:50+00:00

Introduction: Alopecia Areata (AA) is an autoimmune disease characterized by unpredictable, non-scarring hair loss. In the ALLEGRO phase 2b/3 randomized, placebo-controlled clinical trial, ritlecitinib 50mg demonstrated a significantly greater proportion of patients achieving 80% or more scalp hair coverage at 24 weeks compared to placebo. In June 2023, the FDA approved ritlecitinib (50mg) for treatment of severe AA in adults and adolescents 12 years and older. This study aims to address how ritlecitinib is being integrated into real-world practice by assessing the characteristics of patients prescribed ritlecitinib within the first three months following approval.

Methods: This was a retrospective observational study analyzing data from the Komodo Healthcare Map (TM) dataset (Jan 2016-Sept 2023). Komodo Healthcare Map is comprised of open and closed claims for more than 330M lives in the US. The sample included patients aged ≥12 years with ≥1 prescription for ritlecitinib on or after June 23, 2023 (first prescription date defined the index date), ≥1 diagnoses of AA on or before the index date, and ≥12 months of continuous enrollment/eligibility proxy prior to study entry. Clinical characteristics, comorbidities, and AA treatment history were assessed over the 12-month pre-index period. All variables were analyzed descriptively and stratified by age (adolescent: 12-17, adult: ≥18).

Results: Among the 150 patients included, 72% were prescribed ritlecitinib by a dermatologist. Over half were female, 52% were adolescents, and 78% were commercially insured. Approximately 30% of patients had alopecia totalis/alopecia universalis (AT/AU); 11% had ≥1 other autoimmune disorder, 23% had ≥1 atopic disorder, and 21% had ≥1 mental/emotional disorders. In the 12 months prior to receiving ritlecitinib, 34% of adolescents received no AA treatments, 30% received systemic immunomodulators (19% Janus kinase inhibitors [JAKi], 13% other systemic immunomodulators), and 20% received topical corticosteroids. Among adults, 24% had no evidence of prior AA treatments, 35% received injectable corticosteroids, and 35% received systemic immunomodulators (21% baricitinib, 13% other JAKi, and 7% other systemic immunomodulators) during the pre-index period. Of those who had received a prior treatment, the mean time between the last days’ supply of the prior therapy and the start of ritlecitinib was 51 days.

Conclusion: In the first 3 months following the US approval, ritlecitinib was prescribed to a broad range of patients; including adolescent and adults; those with and without prior treatments; and those with and without various comorbidities. This suggests that ritlecitinib may provide new opportunities to (re)engage in AA-directed care.

Funding: this study was funded by Pfizer Inc.

Efficacy of Ritlecitinib in Patients with Alopecia Areata by Extent of Hair Loss: Results from the Phase 2b/3 and Phase 3 ALLEGRO Clinical Trials

2024-11-08T16:57:55+00:00

Introduction: Ritlecitinib, a dual JAK3/TEC family kinase inhibitor, demonstrated efficacy and safety in patients ≥12 years old with AA and ≥50% scalp hair loss in the phase 2b/3 ALLEGRO study. This post hoc, pooled analysis of the ALLEGRO-2b/3 and phase 3 ALLEGRO-LT studies evaluated the efficacy of ritlecitinib in patients with alopecia areata (AA) by extent of baseline scalp hair loss through Month 24.

Methods: Patients aged ≥12 years with AA and ≥50% scalp hair loss who received ritlecitinib 50 mg daily in ALLEGRO-2b/3 and rolled over to ALLEGRO-LT (continued to receive 50 mg) were included. Outcomes included the proportions of patients achieving response based on Severity of Alopecia Tool [SALT] score ≤20 (≤20% scalp hair loss), ≥2-grade improvement in eyebrow assessment [EBA] score (among patients with abnormal score at baseline), and ≥2-grade improvement in eyelash assessment [ELA] score (among patients with abnormal score at baseline). Patients were stratified by extent of scalp hair loss at baseline, defined as severe AA (SALT score 50-94) or very severe AA (SALT score 95-100), as per the Alopecia Areata Investigator Global Assessment (AA-IGA). Data as observed and imputed (last observation carried forward [LOCF]) are reported at the cutoff date (December 9, 2022).

Results: Of 191 patients included, 66 (34.6%) had severe AA and 125 (65.4%) had very severe AA at baseline. At Month 12, 64.4% and 34.3% (observed) and 60.6% and 29.6% (LOCF) of patients with severe AA and very severe AA, respectively, achieved SALT ≤20. At Month 24, these proportions increased to 70.2% and 54.8% (observed) and 63.6% and 36.8% (LOCF), respectively. EBA response was achieved in 54.6% and 46.9% (observed) and 52.8% and 42.4% (LOCF) of patients with severe AA and very severe AA, respectively, at Month 12; at Month 24, the proportions were 60.9% and 56.5% (observed) and 50.0% and 45.8% (LOCF). ELA response was achieved in 60.7% and 40.5% (observed) and 61.3% and 38.0% (LOCF) of patients with severe AA and very severe AA, respectively, at Month 12; at Month 24, the proportions were 70.0% and 45.3% (observed) and 61.3% and 38.0% (LOCF).

Conclusion: Ritlecitinib 50 mg daily achieves scalp, eyebrow, and eyelash hair regrowth in patients with severe and very severe AA.

Funding: This study was funded by Pfizer Inc

Race and Ethnicity Sub-Groups of Alopecia Areata Patients have Differing Clinical Characteristics: TARGET-DERM AA

2024-11-13T17:00:47+00:00

Introduction Alopecia areata (AA) is a chronic, autoimmune disease that disproportionately impacts particular subgroups.¹

Methods United States and Canadian clinics enrolled participants in the TARGET-DERM AA registry (December 2021 - June 2024, data collection ongoing). Those who completed a baseline patient questionnaire [self-reported race / ethnicity, Patient Global Impression of Severity (PGIS-AA)] and clinician-reported outcome measures [Severity of Alopecia Tool (SALT), ClinRO Measure for Eyebrow / Eyelash Hair Loss] were summarized.

Results Of the 267 AA patients, 61.4% were female; 53.2% were adults, 28.5% identified as Hispanic, 52.1% Non-Hispanic (NH)-White, 8.6% NH Black and 6.4% as NH Asian. 47.1% of NH Asian patients had severe disease (SALT>50) and represented the group with the highest proportion of SALT>50, followed by 34.8% of NH Black, 31.7% NH White, and 19.7% Hispanic AA patients. 47.1% of NH Asian patients reported PGIS-AA ‘severe/very severe’ disease, 41.9% of NH White, 39.1% of NH Black and 27.6% of Hispanic AA patients. Eyebrow involvement was highest in NH Whites (44.6%), followed by NH Asian (41.2%), NH Black (34.8%), and Hispanic AA patients (26.3%). Eyelash involvement was highest in NH Black patients, followed by NH White, NH Asian, and Hispanic patients (39.1%, 34.7%, 35.3%, and 17.1%, respectively).

Discussion In this large real-world cohort, there are differences in clinician reported measures by race/ethnicity subgroups. NH-Asian patients represented the largest proportion of patients with patient and clinician-reported severe disease, and clinician-reported eyebrow / eyelash involvement was most prevalent in NH White patients. Hispanic patients had the smallest proportion with severe SALT, eyebrow and eyelash involvement. Additional research is required to better characterize AA and health-related quality of life burden in non-White AA patients.

Demographics and Disease Characteristics of Patients with Alopecia Areata with Comorbid Atopic Dermatitis, Vitiligo or Anxiety/Depression: TARGET-DERM AA

2024-11-13T15:33:19+00:00

Introduction Alopecia areata (AA) is a chronic autoimmune disease. Common AA comorbidities include atopic dermatitis (AD), vitiligo, anxiety and depression (AnxDep). TARGET-DERM AA is an ongoing longitudinal, real-world study of United States and Canadian AA patients. The purpose of this analysis is to assess characteristics among AA patients with and without the above comorbidities.

Methods At enrollment (December 2021-June 2024), patients reported outcomes (including comorbidities, Patient Global Impression of Severity-AA, and clinician-reported outcome measures: Severity of Alopecia Tool, Measure for Eyebrow/Eyelash Hair Loss). Characteristics were compared across subgroups.

Results Of the 267 AA patients with completed patient questionnaires at enrollment, 61.4% were female; 24.4% were aged <12 years, 13.7% 12-17, and 61.7% 18 or older. Overall, 21.0% self-reported an AD diagnosis (19.7% of pediatric, 11.1% of adolescent, and 25.4% of adult AA patients), 7.1% vitiligo (7.0% of pediatric, 3.7% of adolescent, and 8.5% of adult AA patients) and 44.9% AnxDep (21.1% of pediatric, 40.7% of adolescent, and 58.5% of adult AA patients).

42.1% of patients with comorbid vitiligo had severe AA disease (SALT>50) and 27.8% patients without comorbid vitiligo had SALT>50. 28.6% of those with comorbid AD had SALT>50 compared to 28.9% of those not reporting AD, with 30.0% of AnxDep and 27.9% of non-AnxDep having SALT>50, all p>0.2.

42.1% of patients with comorbid vitiligo reported PGIS-AA ‘severe/very severe’ disease, with 41.1% of patients with comorbid AD and 42.5% of patients with comorbid AnxDep reporting severe/very severe AA disease, all numerically higher than patients without comorbid vitiligo (36.3%), AD (35.6%), and AnxDep (31.9%), all p>.07. Among those with and without vitiligo, 42.1% vs 37.9% had eyebrow involvement, 36.8% vs 30.2% eyelash; considering AD, 35.7% vs 38.9% had eyebrow involvement, 28.6% vs 31.3% eyelash; for AnxDep 39.2% vs 37.4% had eyebrow involvement, 30.8% v 30.6% eyelash, all p>0.5.

Discussion In this real-world cohort of AA patients, the presence of specific comorbidities was not associated with statistically significant differences in clinician reported AA severity, eyebrow or eyelash involvement. Comorbid AnxDep was associated with increased patient-reported AA disease severity. Additional research characterizing how dermatologic and psychiatric comorbidities impact health-related quality of life and patient burden has the potential to inform management decisions.

Generic vs. Disease-Specific Patient Reported Outcome (PRO) Instruments for Assessing HRQoL Burden Among Patients Diagnosed with Alopecia Areata: Evidence from TARGET-DERM AA

2024-11-13T17:24:50+00:00

Introduction Alopecia areata (AA) is a chronic, autoimmune disease characterized by patchy hair loss. Compared to other disease areas, recent work has signaled a potential shortcoming, that generic quality of life (QOL) questionnaires are not sufficiently sensitive to the impact of AA disease severity. This cross-sectional analysis investigates the Short-Form 36, the dermatology life quality index (DLQI), and the Alopecia Areata Patient Priority Outcomes (AAPPO) for similar shortcomings.

Methods Patients of all ages enrolled from December 2021 to June 2024 in TARGET-DERM AA (data collection on-going) in the United States and Canada were grouped by Severity of Alopecia Tool (SALT) score (1-20, 21-49, or 50-100). At enrollment, patients completed the AAPPO and DLQI questionnaire as well as the RAND MOS Short-Form 36. The SF-36 has 8 subdomain scores (vitality, physical function, bodily pain, general health, physical role function, emotional role function, social role function, mental health) along with the physical component summaries (PCS), mental component summaries (MCS), and the SF-6D utility index score. The Kruskal-Wallis test compared differences in mean scores across SALT subgroups defined by severity.

Results Of the 141 AA patients, 61.7% were female; 95.0% adults, and 67.4% Non-Hispanic White.

When comparing the SALT 1-20 and the >50 subgroups, significant differences in SF-36 derived mean scores were only observed in the PCS and the physical function score (p<0.05). None of the other scores (MCS, SF-6D, or other SF-36 subdomains) showed any differences. Mean DLQI scores were similar across subgroups (p>.05)

Notably, the hair loss and activity limitation domains of the AAPPO demonstrated significant differences between the patient subgroups (p<.0001 and p<.05, respectively)

Discussion In this real-world cohort, generic QoL instruments, namely the SF-36 and DLQI, did not capture differences in the underlying health-related QoL burden of AA patients with different AA severity. Such differences were clear when HRQoL was measured for AA patients with mild hair loss AAPPO.

A Novel Nutraceutical Gummy for Hair Regrowth in Women: A Case Series

2024-11-07T14:08:05+00:00

Introduction:
Hair loss is a common concern among women, with female pattern hair loss (FPHL) and telogen effluvium (TE) being the most prevalent types. At least 50% of women experience hair loss by age 50 [1]. Many patients turn to nutritional supplements, with one hair loss clinic reporting that up to 81% of their patients use supplements [2]. While various nutraceuticals have demonstrated clinical efficacy in hair regrowth [2], none have been evaluated in gummy form. This case series aims to assess the efficacy of a novel nutraceutical gummy containing a proprietary blend of NAD, pumpkin seed extract, taurine, pea protein, ashwagandha, saw palmetto, and other anti-inflammatory ingredients in promoting hair regrowth in women with FPHL and TE.

Procedure:
Three women, aged 43, 52,64, with diagnoses of FPHL and TE, were included in this series. Each participant consumed two nutraceutical gummies daily for 2 or 3 months. One participant experiencing TE, also took oral minoxidil 1.25 mg daily. Baseline assessments included patient-reported outcomes related to hair shedding and photographic comparisons. Follow-up assessments were performed at 2 or 3 months.

Results:
All three women demonstrated noticeable improvements in hair density and a reduction in hair shedding by the 3-month mark. Participants also reported subjective improvements in hair quality, volume, and overall satisfaction with the product. No adverse effects were observed during the study period.

Conclusion:
This case series suggests that the novel nutraceutical gummy may be an effective, well-tolerated option for promoting hair regrowth in women with FPHL and TE. This nutraceutical can be efficacious as a sole treatment and in conjunction with traditional hair loss medical therapy. These findings highlight the potential for a gummy formulation to provide an accessible, evidence-based treatment for hair loss. Further studies with larger sample sizes are ongoing to validate these results.

Recalcitrant Scalp Psoriasis Successfully Treated with Once-Daily Roflumilast Cream 0.3%

2024-10-31T17:31:53+00:00

Scalp psoriasis is a chronic, immune-mediated skin disease with varying phenotypes and is estimated to affect up to 80% of individuals suffering from psoriasis [1]. The physical symptoms, along with social and emotional impacts of scalp psoriasis can significantly reduce quality of life, necessitating long-term treatment for most patients [3]. Numerous topical and systemic treatments are available for scalp psoriasis, yet the condition remains challenging to manage, underscoring a persistent unmet need for safe and effective therapies [2]. Treatment of the scalp and other hair bearing areas is challenging and can affect the ability to apply topical products and hinder their efficacy [2, 3]. Roflumilast cream 0.3% is a highly selective, non-steroidal and potent topical phosphodiesterase 4 (PDE4) inhibitor approved in 2022 by the FDA for the treatment of psoriasis, including intertriginous disease; in 2023 as a foam for the treatment of seborrheic dermatitis and in 2024, roflumilast cream 0.15% was approved for the treatment of atopic dermatitis. Roflumilast has demonstrated a higher affinity for binding to PDE4 relative to other approved PDE4 inhibitors resulting in greater potency [4, 5]. The results of a phase 3 study investigating roflumilast foam 0.3% in patients with scalp and body psoriasis showed that once daily treatment produced significant clearance of affected areas, rapid improvement in pruritus, and was well-tolerated [6]. Here we report a case involving a 28-year-old female with recalcitrant scalp psoriasis following 10 years of unsuccessful treatment with topical products. Due to the severity of adverse effects experienced with prior therapies, the patient was reluctant to initiate systemic therapy and a trial of once daily topical roflumilast cream 0.3% was initiated. The patient demonstrated rapid improvement after 3 days and clearance of the scalp lesion following daily application for 5 days without any reported adverse effects. Lesions on the patient’s torso also cleared. Upon clearance of lesions, the patient discontinued application of roflumilast cream, and lesions remained clear for several weeks and applies only as needed with any recurrence. Our patient’s case demonstrates the significant potential of roflumilast cream 0.3% in addressing the inflammatory etiology of scalp psoriasis.

Ixekizumab Improves Nail, Scalp, and Skin Response and Quality of Life Independent of Baseline Psoriasis Severity: Results From the Psoriasis in Special Areas (PSoSA) Study

2024-11-07T15:16:29+00:00

Background: Ixekizumab has shown impressive efficacy among patients with nail, skin, and scalp psoriasis. Here, we present real-world data from the PSoSA study evaluating effectiveness of ixekizumab by cohorts of patients with mild and moderate/severe nail psoriasis.

Methods: PSoSA is an ongoing, prospective, multicenter, single-arm, observational study enrolling adult patients with confirmed diagnosis of moderate-to-severe psoriasis and nail involvement, with or without scalp involvement, initiating ixekizumab in a US dermatology clinic. Assessment of improvements in nail (by modified Nail Psoriasis Severity Index [mNAPSI], with scoring range 0–130), skin (by Psoriasis Area and Severity Index [PASI], with scoring range 0–72), and scalp (by Psoriasis Scalp Severity Index [PSSI], with scoring range 0–72) response and in quality of life (by Dermatology Life Quality Index [DLQI], with scoring range 0–30) were collected at weeks (W) 4, 12, 24, and 52. Percent change was calculated for patients with non-missing baseline values. Data were stratified by nail psoriasis severity at baseline; patients with mNAPSI scores <20 were categorized as mild while those with scores ≥20 were categorized as moderate/severe. In our second interim analysis, we will be reporting data to W24.

Results: Of 182 patients included in the analysis, 101 patients had baseline mNAPSI scores <20 and 81 had scores ≥20. Median percent changes from baseline in mNAPSI response at W4, W12, and W24 were −12.2, −33.3, and −71.9, respectively, for patients with baseline scores <20 and −6.1, −38.7, and −68.6, respectively, for patients with scores ≥20. Median percent changes from baseline in PASI response at W4, W12, and W24 were −60.0, −91.2, and −100.0, respectively, for patients with baseline mNAPSI scores <20 and −62.7, −91.4, and −96.7, respectively, for patients with scores ≥20. Median percent changes from baseline in PSSI response at W4, W12, and W24 were −79.3, −100.0, and −100.0, respectively, for patients with baseline mNAPSI scores <20 and −87.5, −100.0, and −100.0, respectively, for patients with scores ≥20. Median percent changes from baseline in DLQI response at W4, W12, and W24 were −66.7, −77.8, and −89.7, respectively for patients with baseline mNAPSI scores <20, and −57.1, −70.0, and −88.7, respectively, for patients with scores ≥20.

Conclusions: In a real-world setting, patients with moderate-to-severe psoriasis initiating ixekizumab saw major improvements in nail, skin, and scalp response as well as quality of life as early as 4 weeks and sustained through 24 weeks, independent of nail psoriasis severity at baseline.

Deucravacitinib in Plaque Psoriasis: Laboratory Parameters Through 4 Years of Treatment in the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

2024-11-07T21:18:47+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious versus placebo and apremilast and was well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials. At Week 52, patients could enroll in the ongoing POETYK long-term extension (LTE) (NCT04036435) trial and receive open-label deucravacitinib. Changes in blood laboratory parameters known to be associated with Janus kinase (JAK) 1,2,3 inhibitors were evaluated through 4 years of deucravacitinib treatment.

Methods: Changes from baseline in lipid (cholesterol, triglycerides), chemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, creatine phosphokinase [CPK]), and hematology (hemoglobin, lymphocytes, neutrophils, platelets) parameters in the blood known to be affected by JAK1,2,3 inhibitors in clinical trials were evaluated through Week 208 (4 years; data cutoff, November 1, 2023). Treatment discontinuations due to laboratory abnormalities were assessed.

Results: A total of 1519 patients received ≥1 deucravacitinib dose (total exposure, 4392.8 person-years); 1203 (79.2%) had ≥52 weeks and 542 (35.7%) had ≥208 weeks of continuous deucravacitinib exposure (median, 185 weeks). No trends or clinically meaningful mean changes from baseline were observed in any of the above laboratory parameters. In total, 3 patients discontinued treatment due to increased CPK, and 1 patient each discontinued due to lymphopenia, abnormal hepatic function, increased ALT, and increased AST. Discontinuations due to triglyceride elevations were not observed.

Conclusion: In PSO-1/PSO-2/LTE, no trends or clinically meaningful mean changes from baseline were observed in lipid, chemistry, or hematology parameters, in contrast to signature changes (eg, increased cholesterol, creatinine, serum transaminases, CPK, cytopenias) observed with JAK1,2,3 inhibitors. Discontinuations due to laboratory abnormalities noted above were rare (n=7 events) through 4 years of deucravacitinib treatment. Results suggest deucravacitinib treatment does not warrant routine laboratory testing for all patients, in contrast with the requirements for JAK1,2,3 inhibitors, reflecting its selectivity for TYK2.

Deucravacitinib, an Oral Selective Tyrosine Kinase 2 (TYK2) Inhibitor, in Patients with Moderate to Severe Scalp Psoriasis: Efficacy and Safety Results of a Phase 3b/4, Multicenter, Randomized, Double-blinded, Placebo-controlled Trial (PSORIATYK SCALP)

2024-11-07T21:32:07+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. PSORIATYK SCALP, an ongoing, 52-week, phase 3b/4, multicenter, randomized, double-blinded, placebo-controlled trial, evaluated deucravacitinib efficacy/safety in patients with moderate to severe scalp psoriasis, including those with more limited overall psoriasis.

Methods: Adults with moderate to severe scalp psoriasis defined by more focused and objective inclusion criteria (ss-PGA ≥3, scalp surface area involvement ≥20%, and PSSI ≥12 at baseline) and BSA involvement ≥3% were randomized 1:2 to oral placebo or deucravacitinib 6 mg once daily through Week 16. The primary efficacy outcome was ss-PGA 0/1; key secondary outcomes were PSSI 90, change from baseline in scalp-specific itch numeric rating scale (NRS), and sPGA 0/1 at Week 16. Efficacy outcomes were evaluated at Week 16 for the overall population and the subpopulation with global sPGA ≥3. Nonresponder imputation and modified baseline observation carried forward were used for patients who discontinued or had missing data for binary and continuous outcomes, respectively.

Results: 154 patients were randomized (placebo, n=51; deucravacitinib, n=103). Baseline characteristics were similar in each group (placebo: mean BSA 10.0%, PASI 9.4, PSSI 32.2; deucravacitinib: mean BSA 10.5%, PASI 10.2, PSSI 33.5). In the overall population, a higher proportion of patients receiving deucravacitinib versus placebo achieved ss-PGA 0/1 at Week 16 (48.5% vs 13.7%; P<0.0001). Deucravacitinib was superior to placebo for PSSI 90 (38.8% vs 2.0%; P<0.0001) and mean change from baseline in scalp-specific itch NRS (−3.2 vs −0.7; P<0.0001). In the subpopulation (sPGA ≥3), a greater proportion achieved sPGA 0/1 with deucravacitinib versus placebo (51.0% vs 4.3%; P<0.0001). The most common adverse events (AEs) in the deucravacitinib group (≥5%) were nasopharyngitis (14.6%), upper respiratory tract infection (11.7%), acne (9.7%), headache (7.8%), COVID-19 (5.8%), and pustular acne (5.8%). Two serious AEs were reported (1/group); neither was considered treatment related or led to discontinuation.

Conclusion: Deucravacitinib was efficacious and well tolerated in patients with moderate to severe scalp psoriasis, including those with less extensive overall psoriasis (BSA ≥3%). The overall psoriasis response rate (sPGA 0/1) was consistent with POETYK trial results, despite including patients with more limited BSA involvement. Safety findings were consistent with the known deucravacitinib safety profile.

Real-World Achievement of Skin Clearance Targets and Improved Quality of Life With Risankizumab in Psoriasis Patients With Moderate Skin Involvement (BSA ≥ 3–10%)

2024-11-07T21:38:40+00:00

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Deucravacitinib Long-term Efficacy Through 4 Years in Week 16 Placebo Crossover Patients in the Phase 3 POETYK PSO-1, PSO-2, and LTE Program

2024-11-07T21:50:29+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious and well-tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials and through 2 additional years in the POETYK long-term extension (LTE) (NCT04036435) trial in patients treated with deucravacitinib from Day 1 of PSO-1/PSO-2. Here, long-term efficacy was assessed through 4 years in patients who crossed over from placebo to deucravacitinib at Week 16 in PSO-1 or PSO-2 and entered the LTE trial.

Methods: PSO-1 and PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At Week 16, patients randomized to placebo crossed over to deucravacitinib. At Week 52, patients could enroll in the LTE and receive open-label deucravacitinib. Efficacy was evaluated in patients who crossed over from placebo to deucravacitinib at Week 16 of the parent trial and received continuous deucravacitinib through 4 years (Week 208; data cutoff, November 1, 2023). Outcomes included ≥75%/≥90% reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1). Efficacy is reported using modified nonresponder imputation (mNRI) in patients who reached the Week 208 assessment or discontinued before Week 208.

Results: Of 421 patients originally randomized to placebo, 348 crossed over to deucravacitinib at Week 16; 298 completed the parent trials and entered the LTE, with 291 meeting mNRI criteria. Efficacy response rates improved from Week 16 on placebo (PASI 75, 12.0% [95% CI, 8.5%-16.3%]; PASI 90, 3.4% [1.7%-6.2%]; sPGA 0/1, 10.0% [6.8%-14.0%]) through Week 52 on deucravacitinib (PASI 75, 75.2% [70.2%-80.2%]; PASI 90, 47.4% [41.6%-53.1%]; sPGA 0/1, 60.1% [54.5%-65.7%]). Response rates were maintained well through Week 208 (PASI 75, 75.6% [70.0%-81.2%]; PASI 90, 46.6% [40.4%-52.7%]; sPGA 0/1, 55.1% [48.8%-61.4%]).

Conclusion: These findings support the long-term efficacy profile of once-daily oral deucravacitinib for treatment of moderate to severe plaque psoriasis.

Deucravacitinib in Plaque Psoriasis: 4-year Safety and Efficacy Results from the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

2024-11-07T22:19:12+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in the global, 52-week, phase 3 POETYK PSO-1 and PSO-2 parent trials in moderate to severe plaque psoriasis. Upon completion, patients could enroll in the ongoing POETYK long-term extension (LTE) trial. Here, deucravacitinib safety/efficacy are reported through 4 years.

Methods: PSO-1/PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At Week 52, patients enrolled in the LTE received open-label deucravacitinib. Safety was evaluated in patients receiving ≥1 deucravacitinib dose. Exposure-adjusted incidence rate (EAIR) per 100 person-years (PY) was used to assess adverse events (AEs). Efficacy outcomes included PASI 75, PASI 90, and sPGA 0/1 and were analyzed using mNRI in LTE patients receiving continuous deucravacitinib from Day 1 of the parent trials.

Results: 1519 patients received ≥1 deucravacitinib dose; cumulative exposure was 4392.8 PY. EAIRs/100 PY were decreased/comparable from the 1-year to 4-year cumulative period, respectively, for AEs (229.2, 131.7), serious AEs (5.7, 5.0), deaths (0.2, 0.3), discontinuation due to AEs (4.4, 2.2), herpes zoster (0.8, 0.6), malignancies (1.0, 0.9), major adverse cardiovascular events (0.3, 0.3), and venous thromboembolism (0.2, 0.1). Clinical response rates with continuous deucravacitinib (n=513) were maintained from Year 3 (PASI 75, 73.8% [95% CI, 69.6-78.0]; PASI 90, 49.0% [44.4-53.7]; sPGA 0/1, 55.2% [50.5-59.9]) to Year 4 (PASI 75, 71.7% [67.0-76.3]; PASI 90, 47.5% [42.6-52.4]; sPGA 0/1, 57.2% [52.1-62.2]) by mNRI.

Conclusion: Deucravacitinib demonstrated a safety profile through 4 years consistent with 3 years with no emergence of new or long-term safety signals. Efficacy was maintained through 4 years in patients receiving continuous deucravacitinib from Day 1 in PSO-1/PSO-2.

Real-world Patient Use and Perception, Satisfaction, and Adherence with a Calcipotriol and Betamethasone Dipropionate PAD-cream for the Treatment of Plaque Psoriasis

2024-11-08T14:38:51+00:00

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 (TYK2) Inhibitor, in Patients With Moderate to Severe Scalp Psoriasis: Improvement in Scalp-Related Quality of Life and Symptoms in the Phase 3b/4 Multicenter, Randomized, Double-Blinded, Placebo-Controlled PSORIATYK SCALP Trial

2024-11-08T15:58:48+00:00

Introduction: PSORIATYK SCALP (NCT05478499)—an ongoing 52-week, phase 3b/4, multicenter, randomized, double-blinded, placebo-controlled trial—assesses the efficacy and safety of deucravacitinib in patients aged ≥18 years with moderate to severe scalp psoriasis (Psoriasis Scalp Severity Index ≥12, scalp-specific Physician Global Assessment ≥3, scalp surface area involvement ≥20%, and body surface area [BSA] involvement ≥3%). We assessed Week 16 patient-reported outcomes using Scalpdex, a validated, scalp-specific quality-of-life instrument, and numeric rating scales (NRSs) for scalp-specific symptoms.

Methods: Patients were randomized 1:2 to placebo or deucravacitinib 6 mg for 16 weeks, stratified by previous biologic use (yes or no) and body weight (<90 or ≥90 kg). Changes from baseline in Scalpdex total score and NRS scores for scalp-specific itch, pain, and flaking were assessed with an analysis of covariance (ANCOVA) model with treatment and randomization stratification factors as fixed effects and the baseline value as a covariate. Scalpdex total score change from baseline was further assessed in BSA subgroups (BSA 3–10%, BSA >10%), using an ANCOVA model with treatment as a fixed effect and the baseline value as a covariate. P values are nominal.

Results: Mean baseline scores (placebo: n=51; deucravacitinib: n=103) indicated severe impact on quality of life (Scalpdex total score >44.0) and moderate to severe symptoms (NRS ≥4.0). At Week 16, adjusted mean change from baseline (95% CI) in Scalpdex total score was greater in patients receiving deucravacitinib versus placebo (−22.3 [−26.1, −18.6] vs −10.5 [−15.7, −5.2]; P=0.0003). Changes from baseline (95% CI) in scalp-specific NRS measures were greater in patients receiving deucravacitinib versus placebo (itch: −3.2 [−3.7, −2.7] vs −0.7 [−1.4, 0.0]; pain: −2.1 [−2.6, −1.6] vs −0.1 [−0.8, 0.5]; flaking: −3.9 [−4.5, −3.4] vs −1.0 [−1.8, −0.2]; all P<0.0001). In each BSA subgroup, patients receiving deucravacitinib versus placebo reported greater Week 16 change from baseline in Scalpdex total score (BSA 3–10%: −19.8 [−23.9, −15.6] vs −10.5 [−16.1, −4.9]; P=0.0096; BSA >10%: −26.2 [−33.2, −19.3] vs −11.2 [−22.3, 0.0]; P=0.0263).

Conclusion: Deucravacitinib was efficacious in improving scalp-specific psoriasis symptoms and quality of life. Furthermore, scalp-related quality of life was improved in patients receiving deucravacitinib in both BSA subgroups.

Treatments Used Among Patients with Psoriasis: A First Look at a New Patient-Centered Psoriasis Registry

2024-11-08T16:10:42+00:00

Introduction: Psoriasis management in the US has changed substantially, with increasing treatment options including new topical, oral, and biologic medications. The objective of this study was to examine the demographics, disease characteristics, and treatment usage in the first patients enrolled in the new patient-centered psoriasis registry, the FORWARD Psoriasis Registry.

Methods: Adult patients with psoriasis were recruited from dermatology offices as part of a national practice group, through a patient support program for deucravacitinib, and online from the FORWARD registry website between August and December 2023. Patients were not required to be on therapy for psoriasis. We descriptively report demographics, disease characteristics, and current treatments at enrollment.

Results: A total of 702 patients met inclusion criteria and completed the full enrollment questionnaire. Mean age was 53 years and 66% were female; mean BMI was 30 (SD 7); 88% self-reported as White and 6% as Hispanic. A diagnosis of psoriatic arthritis was reported by 28%. Most (75%) had private insurance. Median psoriasis duration was 10 (IQR 3–23) years. 85% had plaque psoriasis, 19% guttate, 14% inverse, 6% generalized pustular, and 3% erythrodermic. Body surface area as assessed by the PREPI questionnaire was minimal (<1% BSA) in 21%, mild (1%–2%) in 39%, moderate (3%–10%) in 34%, and severe (>10%) in 6%. The most commonly used therapies included IL-23 inhibitors (11%), IL-17 inhibitors (8%), apremilast (7%), and TNF inhibitors (5%). Additionally, 14% of the cohort were using deucravacitinib; 62% reported using topicals, and 48% reported use of any systemic agent.

Conclusion: The FORWARD psoriasis registry represents a new patient-centered approach and proof of concept for studies seeking to understand the natural history of the disease, treatment outcomes, and treatment needs relevant for individuals with psoriasis, and long-term outcomes related to comorbidities.

Provider Burden Associated With Apremilast Adverse Events

2024-11-08T16:28:13+00:00

Introduction: In December 2021, the US Food and Drug Administration (FDA) expanded its initial approval for apremilast to include moderate and severe cases of psoriasis. However, real-world epidemiology data regarding the use of apremilast, the influence of adverse events (AEs), and the burden of AEs on managing physicians, has been lacking. This retrospective, observational, multisite study aimed to describe real-world patient characteristics, AEs (including diarrhea, nausea, and headache), and healthcare provider-level burden associated with the psoriasis treatment apremilast in the US.

Methods: Dermatologists abstracted medical record data for adults treated with apremilast on or after January 1, 2018, who had ≥3 months of data available. Dermatologist and patient characteristics, including demographics and clinical characteristics, AEs, and provider burden in managing AEs were summarized using descriptive statistics.

Results: Forty-seven dermatologists nationwide responded to a survey and conducted a chart review of 308 patients. Dermatologists practiced in various US geographic regions. The most common practice setting was in a private community with 2 to 5 physicians (34.0%). Most patients were White (74.4%), non-Hispanic (86.0%), and male (55.2%). The mean age at diagnosis was 43.6 years (SD, 16.8 years). AEs occurred in 29.2% of patients, with the most common being diarrhea (16.2%), followed by nausea (13.6%) and headache (4.9%). Diarrhea mostly occurred ≤30 days into treatment (87.2%) and resulted in 1 additional office visit (39.5%) and 3 phone calls per patient to their providers (34.9%). Nausea mostly occurred within 30 days (70.2%) and resulted in 1 additional visit (29.7%) and 1 phone call per patient (35.1%). The burdens of managing both diarrhea and nausea were similar, although diarrhea resulted in more phone calls to the healthcare provider.

Conclusion: Diarrhea and nausea were common and resulted in an additional time and resource burden on dermatologists and their staff. Future research on the AE burden on providers and patients related to apremilast is needed.

Deucravacitinib in Moderate to Severe Plaque Psoriasis: Comorbidities and Use of Prior and Concomitant Medication in Patients Enrolled in the Phase 3 POETYK PSO-1 and PSO-2 Trials

2024-11-08T17:10:12+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in two global, phase 3 trials, POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751), in moderate to severe plaque psoriasis. Here, we evaluate the comorbidities present at baseline and use of prior and concomitant medications in the pooled POETYK PSO-1 and PSO-2 trial populations to more comprehensively describe the medical history of individuals who participated in the deucravacitinib phase 3 trials.

Methods: In POETYK PSO-1 and PSO-2, adults with moderate to severe plaque psoriasis were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. The rates of baseline comorbidities and medications received before and concomitantly with deucravacitinib in the pooled POETYK PSO trials were assessed. Medication classes evaluated included antidiabetic, antihypertensive and cardiovascular, lipid-reducing, anti-anxiety/depression, and oral contraceptive therapies.

Results: Baseline patient demographics were similar across treatment arms. Metabolism and nutrition disorders were reported most often in each treatment arm (placebo, 42.7%; deucravacitinib, 39.2%; apremilast, 38.4%), followed by vascular disorders (33.7%, 34.9%, and 31.8%, respectively). Hypertension was the most common baseline medical condition (placebo, 30.3%, deucravacitinib, 32.8%, and apremilast, 29.1%), with obesity, hyperlipidemia, type 2 diabetes mellitus, and seasonal allergies each reported in 10% to 12% of patients in at least one treatment arm. Antihypertensive and cardiovascular agents, lipid-reducing agents, and antidiabetic agents were the most commonly reported medications.

Conclusion: The phase 3 POETYK PSO trials enrolled adults with moderate to severe plaque psoriasis with a range of comorbidities consistent with the real-world population of patients with psoriasis. Medication classes used by patients were consistent with the comorbidities reported at baseline in both trials.

Efficacy of Deucravacitinib in Plaque Psoriasis Across a Range of Body Surface Area Involvement: Post hoc Analysis of the Randomized, Double-Blinded, Placebo-Controlled, Phase 3b/4 PSORIATYK SCALP Trial

2024-11-08T17:27:26+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Scalp involvement affects approximately 80% of patients with plaque psoriasis. PSORIATYK SCALP (NCT05478499) is an ongoing, 52-week, multicenter, phase 3b/4 trial evaluating deucravacitinib in patients with moderate to severe scalp psoriasis, including those with a range of total body surface area (BSA) involvement (≥3%). These patients are candidates for systemic therapy, according to the AAD/NPF and IPC treatment guidelines. This post hoc analysis assessed efficacy in overall body psoriasis.

Methods: Adults (age ≥18 years) with moderate to severe scalp psoriasis (scalp-specific Physician Global Assessment [PGA] ≥3, scalp surface area involvement ≥20%, and Psoriasis Scalp Severity Index ≥12 at baseline) and BSA involvement ≥3% were eligible for inclusion. Patients were randomized 1:2 to oral placebo (n=51) or deucravacitinib 6 mg once daily (n=103) through Week 16. Stratification factors included prior biologic use and body weight. Outcomes at Week 16 included static PGA score of 0 (clear) or 1 (almost clear) (sPGA 0/1), change from baseline in Psoriasis Area and Severity Index (PASI), and change from baseline in whole-body itch numeric rating scale (NRS). Nonresponder imputation (binary outcomes) and modified baseline observation carried forward (continuous outcomes) were used for patients with missing data. All P values are nominal.

Results: Baseline characteristics were similar between groups (deucravacitinib: mean [SD], BSA 10.5% [9.6%], PASI 10.2 [6.7], whole-body itch NRS 5.8 [2.8]; placebo: mean [SD], BSA 10.0% [8.1%], PASI 9.4 [5.6], whole-body itch NRS 5.8 [2.4]). Baseline total BSA involvement was 3%-10% in most patients (deucravacitinib, 68.0%; placebo, 74.5%). At Week 16, a significantly higher proportion of patients receiving deucravacitinib versus placebo achieved sPGA 0/1 (47.6% [95% CI, 37.6%-57.6%] vs 3.9% [0.5%-13.5%], respectively; P<0.0001). Similarly, patients treated with deucravacitinib achieved greater decreases in adjusted mean change from baseline in PASI (−6.4 [95% CI, −7.3 to −5.5] vs −1.3 [−2.6 to −0.1]; P<0.0001) and whole-body itch NRS (−2.9 [−3.4 to −2.4] vs −0.4 [−1.1 to 0.3]; P<0.0001).

Conclusion: In the phase 3b/4 PSORIATYK SCALP trial, deucravacitinib was efficacious in improving overall psoriasis. Efficacy was consistent with the results observed in the phase 3 POETYK PSO-1/PSO-2 trials, despite including patients with less extensive total BSA involvement.

Efficacy of Deucravacitinib in Moderate to Severe Scalp Psoriasis: Analysis of Complete Clearance of Scalp Disease and Symptoms

2024-11-08T17:37:37+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Scalp psoriasis occurs in ~80% of patients; is associated with itching, flaking, pain, and bleeding; disproportionately reduces quality of life; and is challenging to treat with topical agents. PSORIATYK SCALP (NCT05478499), an ongoing, 52-week, phase 3b/4, multicenter, randomized, double-blinded, placebo-controlled trial, evaluated the efficacy and safety of deucravacitinib in patients with moderate to severe scalp psoriasis. This post hoc analysis compared the efficacy of deucravacitinib versus placebo in the achievement of complete clearance of scalp disease and symptoms.

Methods: Adults with moderate to severe scalp psoriasis (scalp-specific Physician Global Assessment [ss-PGA] score ≥3, scalp surface area involvement ≥20%, and Psoriasis Scalp Severity Index [PSSI] score ≥12 at baseline) and body surface area involvement ≥3% were randomized 1:2 to oral placebo (n=51) or deucravacitinib 6 mg once daily (n=103) through Week 16. Stratification factors included prior biologic use and body weight. At Week 16, all patients received open-label deucravacitinib treatment through Week 52. Outcomes included the proportions of patients who achieved an ss-PGA score of 0 (clear) (ss-PGA 0), 100% improvement from baseline in PSSI (PSSI 100), and scores of 0 (clear) in each of the scalp-specific numeric rating scales (ss-NRS) for itching, pain, and flaking. Nonresponder imputation was used for patients who had missing data. P values are nominal.

Results: Baseline disease characteristics, including ss-PGA, PSSI, and ss-NRS itching, pain, and flaking scores, were similar between the 2 groups. At Week 16, a significantly higher proportion of patients receiving deucravacitinib versus placebo achieved ss-PGA 0 (25.2% vs 3.9%, respectively; P=0.001) and PSSI 100 (27.2% vs 2.0%; P=0.0002). A significantly higher proportion of patients treated with deucravacitinib versus placebo achieved ss-NRS 0 for itching (16.0% vs 0.0%, respectively; P=0.003), pain (37.2% vs 13.3%; P=0.004), and flaking (22.5% vs 2.0%; P=0.001).

Conclusion: In this scalp-specific trial, deucravacitinib treatment was associated with greater complete clearance of scalp disease and symptoms at 16 weeks compared with placebo in patients with significant scalp disease.

Bimekizumab Efficacy and Safety Over 48 Weeks in US and Canadian Patients with Psoriasis who had a Treatment Interruption After 3 Years of Treatment: Results from BE RADIANT

2024-11-08T18:03:57+00:00

Bimekizumab 4-year Efficacy in High-impact Areas in Moderate to Severe Plaque Psoriasis: Pooled Results from BE BRIGHT

2024-11-08T18:05:17+00:00

Bimekizumab Long-term Efficacy in Patients with Moderate to Severe Plaque Psoriasis After Switching From Adalimumab, Ustekinumab, or Secukinumab: Results from Up to 4 Years of Total Treatment from BE BRIGHT and BE RADIANT

2024-11-08T18:05:46+00:00

Bimekizumab Clinical Efficacy in Important Body Regions and Health-related Quality of Life in Patients with Plaque Psoriasis: Data from Four Phase 3/3b Comparator-controlled Trial Periods

2024-11-08T18:05:57+00:00

Bimekizumab Efficacy and Safety in Patients With Psoriatic Arthritis Who Had Skin and Nail Psoriasis at Baseline: Up to 2-year Results From Two Phase 3 Studies

2024-11-08T19:36:06+00:00

Introduction: Bimekizumab (BKZ), a humanized anti-IL17F anti-IL17A antibody has demonstrated efficacy and tolerability to 1 year in patients with psoriatic arthritis (PsA) and psoriasis.¹ Nail psoriasis is associated with increased PsA risk, more severe disease and decreased quality of life, in patients with psoriasis.^2,3

Here, efficacy and safety of BKZ treatment are reported to 2 years in patients with PsA, skin involvement and nail psoriasis in two phase 3 trials.

Methods: BE OPTIMAL (NCT03895203; bDMARD-naïve) and BE COMPLETE (NCT03896581; TNFi‑IR) assessed subcutaneous BKZ 160 mg Q4W in patients with PsA. Placebo (PBO) patients switched to BKZ (PBO/BKZ) at Wk16. BE OPTIMAL included a reference arm (adalimumab [ADA] 40 mg Q2W); ADA patients switched to BKZ at Wk52 (ADA/BKZ). BE OPTIMAL Wk52 and BE COMPLETE Wk16 completers could enter BE VITAL (open-label extension; NCT04009499), where all patients received BKZ.

Post-hoc data reported for patients with baseline skin involvement (≥3% body surface area) and nail psoriasis (modified Nail Psoriasis Severity Index >0). Efficacy reported to Wk104 of BE OPTIMAL/Wk100 of BE COMPLETE. Missing data imputed using non‑responder, multiple or worst-category imputation.

Safety data are reported for all patients treated with BKZ.

Results: Of 263/852 (30.9%) bDMARD-naïve and 159/400 (39.8%) TNFi-IR patients with baseline skin and nail psoriasis, 230 (87.5%) and 136 (85.5%) patients completed Wk104/Wk100.

Efficacy responses at Wk52 on BKZ were sustained to Wk104/Wk100 across joint, skin, nail, physical function and composite outcomes. ADA/BKZ cohort showed sustained responses after switch.

For bDMARD-naïve and TNFi-IR patients on BKZ, the exposure-adjusted incidence rates per 100 patient-years (EAIR/100 PY) for ≥1 treatment-emergent adverse event (TEAE) were 154.9 and 78.8, respectively; and for serious TEAEs, 6.6 and 5.2 respectively. None of the reported Candida infections were serious or systemic; all 3 deaths were deemed unrelated to treatment.

Conclusions: BKZ treatment demonstrated sustained clinical efficacy to 2 years in patients with PsA, skin involvement and nail psoriasis, regardless of prior TNFi treatment. BKZ was well tolerated; consistent safety profile to previous reports.¹

Bimekizumab Safe and Effective Self-administration Using 2 mL Devices by Patients with Moderate to Severe Plaque Psoriasis: Results from Two Multicenter, Randomized, Open-label Studies

2024-11-08T20:15:57+00:00

Introduction: Safe and effective self-injection of subcutaneous bimekizumab (BKZ) in patients with moderate to severe plaque psoriasis using a 1 mL safety syringe (sy) or auto-injector (AI) has previously been associated with an overall positive patient experience.¹ Here, the ability of patients to safely and effectively self-administer subcutaneous BKZ using a 2 mL sy or AI is reported.

Methods: DV0002 (North America) and DV0006 (Germany, Hungary and Poland) were sub-studies of the phase 3 open-label extension (OLE) study, BE BRIGHT.^1,2 Included patients received BKZ 320 mg every 4 weeks (Q4W) or Q8W based on treatment regimen and Psoriasis Area Severity Index (PASI) response at BE BRIGHT entry. Patients were randomized 1:1 to BKZ-sy-2 mL or BKZ-AI-2 mL, and performed self-injections (after training in the self-injection technique) at baseline and Wk8. Safe and effective self-injection defined as complete dose delivery of BKZ and absence of adverse events related to the device which led to study withdrawal.

Primary and secondary objectives were to assess patients’ ability to safely and effectively self-administer BKZ at Wk8 and baseline, respectively. Other objectives included to evaluate patient experience of self-injection, using the injection site pain visual analog scale (VAS; 0 [no pain]–100 [worst possible pain]) and the Self-Injection Assessment Questionnaire (SIAQ; subscale scores ranged 0-10 [higher scores better]), and the post-use structural and mechanical integrity of each device. Data analyzed using two full analysis sets (BKZ-sy-2 mL and BKZ-AI-2 mL) and reported for the combined BKZ dose groups (BKZ Total) using observed cases.

Results: In DV0002, 19 patients each were randomized to use BKZ-sy-2 mL and BKZ-AI-2 mL. All patients using BKZ-sy-2 mL (n=19) self-injected BKZ safely and effectively at baseline and Wk8. All (n=19) and 94.7% (n=18/19) of patients using BKZ-AI-2 mL self-injected BKZ safely and effectively at baseline and Wk8, respectively. In DV0006, 44 and 45 patients were randomized to use BKZ-sy-2 mL and BKZ-AI-2 mL, respectively. All patients using BKZ-sy-2 mL (n=44) and BKZ-AI-2 mL (n=45) safely and effectively self-injected BKZ at baseline and Wk8.

In DV0002/6, median pre-injection and post-injection SIAQ scores were ≥7.5 across both devices, and >9.0 for feelings about injections, self-image, and injection-site reactions subscales. In DV0002/6, low median VAS scores across both devices indicate variable but generally low pain. All devices maintained their structural and functional integrity post-use. One device deficiency complaint was received.

Conclusions: A positive self-administration experience was associated with the 2 mL devices, as reported with 1 mL devices,¹providing patients with an option to self-administer a single injection of BKZ.

Bimekizumab 4-year Maintenance of Responses in Week 16 Responders with Moderate to Severe Plaque Psoriasis: Results from the BE BRIGHT Open-label Extension Phase 3 Trial

2024-11-08T20:32:50+00:00

Introduction: Psoriasis is a chronic disease where loss of response to biologic therapies over time is commonly observed; studying long-term efficacy of new treatments is important.¹ Maintenance of high responses to bimekizumab (BKZ) has been reported through 3 years (yrs) in patients with moderate to severe plaque psoriasis.² This study evaluates the maintenance of clinical responses over 4 years among patients with moderate to severe plaque psoriasis who achieved complete or near-complete skin clearance after 16 weeks (wks) of BKZ treatment and entered the BE BRIGHT open-label extension. Responses were compared over 4 years between all patients who were randomized to BKZ and continued to receive bimekizumab (320 mg every 4 wks [Q4W] or Q8W) in the open-label extension, and those who received the BKZ dosing regimen that is approved for most patients: BKZ 320 mg Q4W to Wk 16 followed by 320 mg Q8W.

Methods: Patients completing the 52-wk BE VIVID or 56-wk BE SURE/BE READY phase 3 trials could enter the BE BRIGHT open-label extension (OLE).^2–5

Maintenance of PASI90/PASI100 (≥90%/100% improvements from baseline in Psoriasis Area and Severity Index) to Yr4 (OLE Wk144) was assessed in Wk16 responders. Analyzed patients were randomized to BKZ 320 mg Q4W to Wk16, received BKZ Q4W or Q8W until OLE entry, then BKZ Q4W or Q8W dependent on PASI response/prior dose (BKZ Total); the subset who received BKZ Q4W/Q8W/Q8W (initial/maintenance/OLE) were also analyzed. All received BKZ Q8W from OLE Wk48 or at their next scheduled visit.

Patients who discontinued due to lack of efficacy/treatment-related adverse events were considered non-responders; multiple imputation was used for all other missing data (modified non-responder imputation).

Results: Of 989 BKZ-randomized patients, 87.5% achieved PASI90 and 62.7% PASI100 at Wk16 (non-responder imputation). 693 Wk16 PASI90 and 503 PASI100 responders entered the OLE (BKZ Total); 186 and 147, respectively, received BKZ Q4W/Q8W/Q8W. 87.7%/73.3% of Wk16 PASI90/PASI100 responders maintained their responses to Yr4 (BKZ Total). In the Q4W/Q8W/Q8W subset, 89.0%/76.7% maintained their responses to Yr4.

Conclusions: Among Wk16 responders, high efficacy responses were sustained through 4 yrs of BKZ treatment, including patients who received the approved Q4W/Q8W/Q8W dosing regimen.

Brodalumab Versus Ustekinumab in Obese Patients With Moderate-to-Severe Plaque Psoriasis

2024-11-09T14:45:59+00:00

Introduction: Obesity is associated with psoriasis severity and decreased efficacy of psoriasis therapy.¹ Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.² This post hoc analysis evaluated clinical outcomes of treatment with brodalumab in obese versus nonobese participants with moderate-to-severe plaque psoriasis from phase 3 randomized controlled studies (AMAGINE-1/-2/-3).

Methods: Subgroups included in this analysis comprised obese (body mass index [BMI] ≥30 kg/m²) and nonobese participants (BMI <30 kg/m²) who received brodalumab 210 mg every 2 weeks (AMAGINE-1/-2/-3) or ustekinumab (AMAGINE-2/-3) through 52 weeks. Outcomes included psoriasis area and severity index 90% and 100% improvement (PASI 90 and 100) and treatment-emergent adverse events (TEAEs).

Results: AMAGINE-1 included 108 obese and 114 nonobese participants receiving brodalumab.³ At week 12, 59.3% and 27.8% of obese participants receiving brodalumab achieved PASI 90 and 100, respectively. Rates further improved by week 52 (PASI 90: 71.1%; PASI 100: 52.6%). At both time points, nonobese participants achieved higher rates of PASI 90 and 100 compared with obese participants. AMAGINE-2/-3 included 91 obese and 157 nonobese participants receiving brodalumab and 131 obese and 185 nonobese participants receiving ustekinumab.⁴ For obese participants receiving brodalumab, rates of PASI 90 and 100 were 74.7% and 49.5%, respectively, at week 12; these rates further improved by week 52 (PASI 90: 87.9%; PASI 100: 64.8%) and were higher compared with those of obese participants receiving ustekinumab (PASI 90: 76.3%; PASI 100: 51.9%). Indeed, regardless of BMI, the percentages of PASI 90 and 100 responders were greater with brodalumab compared with ustekinumab. By week 52, PASI responses were similar among nonobese and obese participants in each respective treatment group. Through 52 weeks, TEAEs per 100 patient-years were reported in participants receiving brodalumab (AMAGINE-1, obese: 370.8, nonobese: 388.7; AMAGINE-2/-3, obese: 366.3, nonobese: 404.4) and ustekinumab (AMAGINE-2/-3, obese: 420.6, nonobese: 366.5).

Conclusion: Regardless of BMI, brodalumab demonstrated sustained efficacy in participants with moderate-to-severe plaque psoriasis with no new safety signals.

Fixed-Combination Halobetasol Propionate 0.01% and Tazarotene 0.045% Lotion and Halobetasol Propionate 0.01% Lotion for Plaque Psoriasis on Areas With Body Hair: Maintenance of Treatment Effect

2024-11-09T14:52:24+00:00

Background: Psoriasis on hair-bearing body areas may be difficult to treat with topical therapy, as hair may reduce penetration of active ingredients.¹ Patients may also experience disease rebound following cessation of corticosteroid therapy.^2,3 An appropriate vehicle for hair-bearing areas may increase penetration, and a combination of corticosteroid and tazarotene may improve maintenance of treatment effect following cessation.^4-6 Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) and HP 0.01% lotion are indicated for treatment of plaque psoriasis in adults^7,8 and contain a vehicle optimized for penetration.^6,9 Previously, a post hoc analysis demonstrated the efficacy and safety of HP/TAZ and HP in treating men with plaque psoriasis on the leg, a representative area with body hair.¹⁰ Here, we expand on the previous study by reporting maintenance of efficacy following treatment cessation in this population.

Methods: In phase 3 trials, participants with moderate-to-severe plaque psoriasis were randomized to treatment or vehicle once daily for 8 weeks (HP/TAZ, n=276; vehicle, n=142; HP, n=285; vehicle, n=145). Participants were assessed at 2-week intervals and at 4 weeks after treatment cessation (week 12).^11,12 In this post hoc analysis, treatment success (≥2-grade improvement in investigator’s global assessment score and score of clear or almost clear); erythema, plaque elevation, and scaling success (≥2-grade improvement for each); and safety were assessed in men with psoriasis on the leg treated with HP/TAZ (n=87) or HP (n=91). Maintenance of effect was defined as the proportion of participants who achieved treatment, erythema, plaque elevation, or scaling success at week 8 and maintained success at week 12. Men were assumed to have leg hair. Treatment comparisons were indirect.

Results: Four weeks after treatment cessation, HP/TAZ–treated participants exhibited increased rates of treatment success (week 8, 35.3%; week 12, 37.2%) and erythema success (week 8, 37.4%; week 12, 48.4%), whereas HP-treated participants exhibited decreased rates (treatment success: week 8, 35.5%; week 12, 23.1%; erythema success: week 8, 50.6%; week 12, 36.5%). HP/TAZ–treated participants exhibited less attrition in plaque elevation and scaling success after treatment cessation (week 8, 57.4% and 56.3%; week 12, 55.1% and 55.8%, respectively) versus HP-treated participants (week 8, 53.1% and 61.7%; week 12, 39.8% and 41.6%, respectively). For all outcomes, a greater proportion of participants receiving HP/TAZ achieved maintenance of effect from weeks 8 to 12 compared with participants receiving HP (range: HP/TAZ, 74%-85%; HP, 56%-62%). No new safety signals were identified.

Conclusions: Following treatment cessation of HP/TAZ, men with plaque psoriasis on the leg experienced further disease improvement and maintained treatment effects at greater rates than those treated with HP, suggesting that tazarotene combined with HP provides prolonged efficacy in hair-bearing areas.

Demonstration of the Clinical Utility of a Psoriasis Precision Medicine Tool: Findings from the MATCH Study Show Altered Physician Behavior Leads to Improved Patient Outcomes

2024-11-11T02:40:30+00:00

Zasocitinib (TAK-279), a Selective, Oral TYK2 Inhibitor, Reduces Body Surface Area Involvement in a Phase 2b Trial in Moderate-to-Severe Plaque Psoriasis

2024-11-14T16:58:43+00:00

Background: Zasocitinib (TAK-279) is an oral, allosteric, and highly selective inhibitor of tyrosine kinase 2 (TYK2). TYK2 mediates signaling from cytokines involved in the pathogenesis of psoriasis and other immune-mediated inflammatory diseases. In a phase 2b trial in patients with moderate-to-severe plaque psoriasis (NCT04999839), zasocitinib was well tolerated and demonstrated safety and efficacy, with a greater proportion of patients achieving skin clearance at doses ≥5 mg compared with placebo, with the two highest doses (15mg and 30mg) showing the strongest responses at Week 12. This analysis further evaluated the efficacy of the 15mg and 30mg doses of zasocitinib using body surface area (BSA) involvement.

Methods: In this randomized, multicenter, double-blind, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive oral zasocitinib (2, 5, 15 or 30mg) or placebo, once daily for 12 weeks. BSA outcome measures assessed at Week 12 were mean change in BSA from baseline, mean percentage change in BSA from baseline and the proportion of patients achieving a BSA threshold of ≤1% by visit. Mean change in BSA from baseline was prespecified.

Results: Baseline mean (standard deviation [SD]) percentage BSA was generally consistent across the zasocitinib 15mg (n=53; 18.3 [10.3]), zasocitinib 30mg (n=52; 22.2 [14.3]) and placebo (n=52; 21.3 [13.6]) groups. Mean percentage BSA decreased as early as Week 2 and continued to decrease through to Week 12 in the zasocitinib groups, whereas scores slightly decreased in the placebo group. At Week 12, mean(SD) percentage BSA was 4.4 (5.3) (least-squares [LS] mean change: −14.7; LS mean percentage change: −72.9%) in the 15mg group, 6.5 (12.5) (LS mean change: −15.7; LS mean percentage change: −73.1%) in the 30mg group and 18.2 (13.6) (LS mean change: −4.0; LS mean percentage change: −19.3%) in the placebo group (p<0.001 for both doses versus placebo). From Week 8 onwards, higher proportions of patients achieved a BSA threshold of ≤1% in the zasocitinib 15mg and 30mg groups than in the placebo group (35.8% and 44.2% versus 0% at Week 12, respectively).

Conclusion: Patients with moderate-to-severe plaque psoriasis who received the two highest doses of zasocitinib (15mg and 30mg) in the phase 2b trial achieved greater reductions in BSA than those who received placebo over 12 weeks. Further investigation of the efficacy and safety of zasocitinib in phase 3 studies in psoriasis is ongoing (NCT06088043; NCT06108544).

Evaluation of Changes in Laboratory Parameters from a Phase 2b Trial of Zasocitinib (TAK-279), an Oral, Selective TYK2 Inhibitor, in Patients with Moderate-to-Severe Plaque Psoriasis

2024-11-14T17:00:42+00:00

Background: Zasocitinib (TAK-279) is an oral, allosteric, and highly selective tyrosine kinase 2 inhibitor. In a recent phase 2b trial (NCT04999839), more patients with moderate-to-severe plaque psoriasis treated with zasocitinib 15 and 30 mg once daily achieved 75% improvement in the psoriasis area and severity index at Week 12 (primary endpoint) than those receiving placebo (PBO; p < 0.001). Here we report an assessment of laboratory parameters from this study.

Methods: In this randomized, multicenter, double-blinded, PBO-controlled study, adults with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive oral zasocitinib (2, 5, 15 or 30 mg) or PBO once daily for 12 weeks. The safety analysis set included all patients who received ≥1 dose of the assigned study treatment. Laboratory parameters assessed throughout the trial included creatine kinase (CK), as well as hematologic (neutrophils, lymphocytes, hemoglobin, platelets), hepatic and renal (alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, estimated glomerular filtration rate), and lipid (cholesterol, triglycerides) parameters.

Results: In total, 259 patients were included in the safety analysis set. Longitudinal changes in all laboratory parameters were generally similar in the PBO and zasocitinib groups. Mean values of most laboratory parameters remained within normal ranges during the study. There was no relationship between zasocitinib treatment and cytopenia. Some CK elevations were observed in both the PBO and zasocitinib groups, but most were transient or reversible and of Common Terminology Criteria for Adverse Events Grade 1 or 2 (Grade ≥2 events occurred in 2 [3.8%], 2 [4.0%], 6 [11.5%], 4 [7.5%] and 3 [5.8%] patients, in the PBO, and 2, 5, 15 and 30 mg groups, respectively), and were not associated with rhabdomyolysis. Mean triglyceride values were slightly higher than normal ranges at baseline and Week 12 in all treatment groups, including PBO, and were mainly asymptomatic, mild-to-moderate elevations. These changes were not accompanied by increases in serum cholesterol levels.

Conclusion: Zasocitinib treatment did not result in adverse changes in hematologic, hepatic, renal or lipid parameters that are associated with Janus kinase (JAK) inhibition, suggesting that the mechanism of action of zasocitinib is distinct from that of JAK1/2/3 inhibition. Further phase 3 studies of zasocitinib in psoriasis are ongoing to confirm these observations (NCT06088043; NCT06108544).

Real-World Switch Rates of Risankizumab and Other Biologics in Psoriasis Patients With Psoriatic Arthritis

2024-11-07T20:42:11+00:00

Background: Psoriatic patients often experience issues with lack of therapeutic efficacy and intolerance, which may result in high levels of treatment switching. This study examined real-world, 12-month switch rates and patient characteristics associated with treatment switching in patients with both PsO and PsA treated with risankizumab and other biologics.

Methods: This analysis used the Merative MarketScan^®Databases (2016–2024) to identify adults from the US who had ≥2 medical claims for PsO, 1 claim for PsA and did not have any other autoimmune condition in the 6 months pre- and post-index period. Patients must have initiated a PsO-approved biologic and have continuous insurance benefits for ≥6 months before and ≥12 months after the biologic initiation date. Switch rates were defined as the proportion of patients who switched to a new biologic or advanced oral in the 12-month follow-up after treatment initiation. Discontinuation and non-adherence were not included in the switch definition. Switch rates were compared between biologics with sufficient sample size (n 100). Univariate logistic regression analyses were conducted to compare switch rates for risankizumab versus other biologics. Multivariate logistic regression analyses were performed to examine the impact of baseline demographic and treatment characteristics on switch rates and determine predictors of switching.

Results: Among 3032 patients, mean age at baseline was 47.4 (SD 10.78) years and 55.4% were female. Overall treatment switch rate at 12-month follow-up was 24.9% (756/3032). Of those treatments with sufficient sample size, patients receiving risankizumab had the lowest switch rate (7.3%; 15/206) compared to all other biologics, including other IL-23 inhibitors (guselkumab 16.7%, P=0.0029), IL-17 inhibitors (ixekizumab 22.4%, P<0.0001; secukinumab 23.7%, P<0.0001), TNF inhibitors (adalimumab 28.3%, P<0.0001; etanercept 35.8%, P<0.0001), and IL-12/23 inhibitors (ustekinumab 22.4%, P<0.0001). Results were similar in multivariate logistic regression analyses after adjusting for variations in baseline characteristics. Predictors of switching at 12 months included female sex (adjusted odds ratio [aOR] [95% CI]: 1.63 [1.36, 1.94]; P<0.0001), baseline anxiety or depression (aOR [95% CI]: 1.47 [1.21, 1.80]; P=0.0001), baseline major adverse cardiovascular event (aOR [95% CI]: 1.47 [1.15, 1.88]; P=0.0023), and prior targeted immunomodulator (TIM) use (aOR [95% CI]: 1.45 [1.20, 1.74]; P=0.0001).

Conclusion: In a real-world setting, switching was common among psoriasis patients with PsA. Risankizumab showed the lowest rate of treatment switching at 12 months, compared with all other biologics. Sex, comorbidities, and prior TIM use were predictors of higher switch rates.