SKIN The Journal of Cutaneous Medicine

Lebrikizumab Improved Skin Signs, Quality of Life, and Showed High Levels of Patient Satisfaction in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis and Skin of Color

Valerie Callender — 2025-03-17

Introduction: Lebrikizumab improved signs and symptoms in patients with skin of color (SoC) and moderate-to-severe atopic dermatitis (AD) after 16 weeks of treatment in ADmirable (NCT05372419), an open-label, Phase 3b clinical trial. Here we report 16-week quality of life (QoL) response and patient satisfaction results in this underrepresented patient population, as well as skin response and QoL response achieved for patients mostly/completely satisfied with treatment.

Methods: At baseline and Week 2, patients received 500-mg lebrikizumab loading doses followed by 250-mg every 2 weeks through Week 16. Concomitant topical therapy was allowed. Patients receiving protocol-defined rescue therapy were discontinued. Key eligibility criteria included: ≥12 years of age, self-reported race other than White, Fitzpatrick Phototype IV-VI, and moderate-to-severe AD. Skin response was assessed using Eczema Area and Severity Index (EASI) and QoL response was assessed using Dermatology Life Quality Index (DLQI). Patients reported satisfaction on the treatment’s ability to treat their AD by responding not satisfied, slightly satisfied, somewhat satisfied, mostly satisfied, or completely satisfied. Endpoints are summarized as observed data. The analysis was descriptive based on all observed data.

Results: At baseline, patients (N=90) had a mean (standard deviation [SD]) EASI of 26.4 (12.2), and n=77 had DLQI of 13.2 (7.4). Patients self-reported their race as Black/African American (77.8%), Asian (11.1%), American Indian/Alaskan Native (6.7%), and Native Hawaiian or Other Pacific Islander (4.4%). Patients had Fitzpatrick Phototypes of IV (43.3%), V (24.4%), and VI (32.2%). At Week 16, 71.7% (43/60) of patients achieved ≥4-point improvement from baseline in DLQI, 57.4% (39/68) achieved DLQI ≤5, and 29.4% (20/68) achieved DLQI 0,1. The mean percentage improvement in DLQI from baseline to Week 16 was 52.7% (n=66). In total, 62.8% (49/78) of patients were mostly/completely satisfied with treatment, while 37.2% (29/78) were somewhat, slightly or not satisfied. Of these 29 patients, 6 (7.7%) were not satisfied with treatment. For EASI 75 Week 16-responders, 74.1% (40/54) were mostly/completely satisfied with treatment and 71.4% (25/35) of EASI 90 responders were mostly/completely satisfied. In terms of QoL, 69.8% (30/43) of patients who achieved ≥4-point improvement from baseline in DLQI were mostly/completely satisfied with treatment, 76.9% (30/39) of DLQI ≤5 responders and 85.0% (17/20) of DLQI 0,1 responders were mostly/completely satisfied.

Conclusion: Lebrikizumab treatment showed improved QoL and high rates of patient-reported treatment satisfaction in SoC patients with moderate-to-severe AD. Patients treated with lebrikizumab who achieved high rates of skin clearance and QoL improvements reported the highest levels of treatment satisfaction.

Half-life-extended monoclonal antibody APG777 for atopic dermatitis: Design of the phase 2 APEX study

Emma Guttman-Yassky — 2025-03-17

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. Results from a phase 1 study in healthy participants suggest a favorable safety and PK/PD profile for APG777, as well as a half-life of 77 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.

Preclinical Potency, Affinity, and Pharmacokinetics of APG990, a Half-Life Extended Antibody Against OX40L

Grant Wickman — 2025-03-17

Background: Signaling through the OX40-OX40L pathway has been implicated in the pathogenesis of many inflammatory conditions, including atopic dermatitis. APG990 is a fully human monoclonal antibody (mAb) designed to bind to OX40L and block inflammatory signaling mediated by the interaction between OX40 and OX40L. APG990 contains YTE amino acid modifications in the Fc region to extend its half-life and a LALA modification to ablate Fc-mediated function.

Methods: Multiple preclinical assays were used to assess the ability of APG990 to bind OX40L, as well as the impact of APG990 on downstream OX40/OX40L binding and signaling. An antibody based on the published sequence of amlitelimab was used as a positive control. The affinity of APG990 for OX40L was measured by surface plasmon resonance (SPR). To investigate the ability of APG990 to inhibit human OX40L binding, an ELISA assay was used to assess APG990 and human OX40 competitive binding to immobilized human OX40L. To investigate the ability of APG990 to inhibit human OX40L-induced signaling, the effects of increasing concentrations of APG990 were assessed on a human OX40 reporter cell line. Activated human primary CD4+ T cells were used to evaluate the concentration-dependent blocking ability of OX40L. Activated human primary CD4+ T cells were used to assess the APG990 concentration-dependent blockage of OX40L-induced IL-2 release. The pharmacokinetics of APG990 were evaluated following a single bolus (SC or IV) of APG990 in cynomolgus monkeys.

Results: APG990 bound OX40L from humans with a KD of 106.38 pM (vs 70.91 for amlitelimab). APG990 inhibited human OX40L binding to OX40 in a concentration-dependent manner, with an IC90 of 6.5 nM (vs 4.7 nM for amlitelimab), and blocked OX40L-induced IL-2 release (IC90 of 2.9 nM for APG990 vs 2.3 nM for amlitelimab). APG990 blocked human OX40L-induced activation of OX40 reporter cells with an IC90 of 4.5 nM (vs 7.8 nM in amlitelimab). In NHPs, APG990 exhibited a mean serum half-life of 26.9 (IV) and 25.5 (SC) days, versus 19.8 (IV) and 22.2 (SC) for amlitelimab APG990 was well-absorbed, with an average bioavailability of 96%.

Conclusions: APG990 demonstrated strong binding affinity for OX40L and effectively blocked inflammatory signaling mediated by the interaction between OX40L and OX40. APG990 has a longer half-life than amlitelimab but similar binding affinity and potency. These results support clinical investigations with APG990 for the treatment of inflammatory conditions, such as atopic dermatitis.

Patient Experience and Preferences for Treatments in Atopic Dermatitis: Results from a US Patient Survey

Ann Quick — 2025-03-17

Background: Recent advances in understanding the molecular mechanisms underlying atopic dermatitis (AD) have led to the development and FDA approval of multiple targeted therapies. Molecular heterogeneity of AD contributes to inconsistent clinical presentation and therapeutic response, which can lead to delays in diagnosis and initiation of appropriate treatment for patients. Adding complexity to the decision-making process, newer targeted systemic treatments are also associated with varied efficacy, safety profiles, and monitoring requirements. More information is needed on patient perspectives of current systemic treatment options to support joint treatment decision-making.

Objectives: To 1) better understand patient attitudes about contemporary AD treatments and experiences and 2) evaluate patient perception of a molecular test to predict treatment response.

Methods: A 31-question survey (IRB-exempt) made available to attendees of the 2024 National Eczema Association Eczema Expo was designed to assess patient perspectives on their treatment for AD, including treatment attributes and experiences. Participation was voluntary and not associated with data presentation.

Results: Of 43 eligible respondents, 74% were 18 to 64 years old and 21% were <18 years of age, with the remaining participants ≥65 years (5%). Approximately 40% (16) of participants reported their AD was previously misdiagnosed and 28% (12) of the participants were biopsied to confirm their AD diagnosis. The top three factors most important to respondents using topical-only or systemic (±topical) medications were itch control (70%), skin clearance (58%), and safety/side effects (50%). For the 22 respondents who used targeted systemics, 23% switched or added another systemic and 32% added topicals. The top two reasons for switching or modifying systemic treatment were insufficient skin clearance and itch control. Patient ratings of how well current therapy met their treatment goals varied extensively. Scaled from 1% (goals not met) to 100% (goals met), patient rankings ranged from 26% - 100% with a median of 68% progress toward goals for those using systemic therapies (± skin-directed therapies). Over 80% of respondents would want, or may consider, taking a test informing them of which targeted systemic would work best for them, thus highlighting a clinical need for personalized therapeutic guidance in AD.

Conclusion: A substantial number of AD patients experience delayed diagnosis. Itch was the most important symptom that respondents desired their medication to address. While topicals and systemic therapies can be effective, AD patients had a wide variety of treatment responses regardless of treatment modality, suggesting a need for a more personalized approach to treatment selection. The majority (80%) of patients would want, or would consider, a test that would direct them towards a more effective therapy for their AD.

Skin Clearance, Duration of Treatment-free Interval, 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

Robert Bissonnette — 2025-03-17

Introduction: In ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA^®, Dermavant Sciences, an Organon Company) once daily (QD) demonstrated superior efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability from ADORING 3. Methods: 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 ADORING 1 or 2 inclusion criteria, received tapinarof cream 1% QD for up to 48 weeks. Endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™]=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Patients entering with vIGA-AD™≥1 received tapinarof until vIGA-AD™=0. Those entering with or achieving vIGA-AD™=0 discontinued tapinarof and were assessed for maintenance of vIGA-AD™=0 or 1 (treatment-free interval). Patients with vIGA-AD™≥2 were re-treated until vIGA-AD™=0. Results: 728 patients enrolled; 83.0% pediatric (2–17 years). Overall, 51.9% entered with or achieved vIGA-AD™=0, and 81.6% entered with or achieved vIGA-AD™=0 or 1 at least once during ADORING 3. 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 treatment-emergent adverse events (TEAEs) were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Trial discontinuations due to TEAEs were low (2.6%). 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, even on sensitive skin. Conclusions: Tapinarof cream monotherapy was well tolerated and demonstrated high rates of complete disease clearance (51.9%) in patients down to age 2 years with AD. After discontinuing tapinarof, clear or almost clear skin was maintained for 79.8 consecutive days. No new safety signals and low rates of trial discontinuation were observed.

Patient-Reported Outcomes with Roflumilast Foam 0.3% in Patients with Psoriasis of the Scalp and Body in the Phase 3 ARRECTOR Trial

Melinda Gooderham — 2025-03-17

Introduction: Patients with psoriasis of the scalp or body consider itch the most burdensome symptom. Roflumilast is a highly potent phosphodiesterase 4 inhibitor under investigation as a novel, once-daily foam for treatment of psoriasis of the scalp and body. The impact of roflumilast foam 0.3% on patient-reported outcomes (PROs) in patients with psoriasis of the scalp and body from the phase 3 trial (ARRECTOR; NCT05028582) are reported here.

Methods: Patients aged ≥12 years with psoriasis of the scalp and body affecting ≤25% of overall body surface area, minimum Scalp-Investigator Global Assessment (S‑IGA) of Moderate, and minimum Body-IGA (B-IGA) of Mild were randomized 2:1 to once-daily roflumilast foam 0.3% or vehicle for 8 weeks. PROs included the Psoriasis Symptom Diary (PSD; ≥18 years only), Scalpdex, Dermatology Life Quality Index (DLQI; ≥17 years only), Scalp Itch- and Worst Itch-Numeric Rating Scale (SI-NRS and WI‑NRS, respectively; each rated from 0 [no itch] to 10 [worst itch imaginable]).

Results: Overall, 281 patients were treated with roflumilast foam 0.3% and 151 were treated with vehicle. In patients with SI-NRS and/or WI-NRS ≥2 at baseline, significantly greater proportions of the roflumilast group than the vehicle group achieved scores of 0 or 1 at Week 8 for SI-NRS (52.3% vs 24.1%; P<0.0001) and/or WI_‑NRS (55.4% vs 19.8%; P<0.0001). Similar improvements were observed in other PROs at Week 8, with a significantly greater proportion of the roflumilast group achieving PSD total scores of 0 (19.6% vs 7.1%; P=0.0012). The roflumilast group also had significantly greater reductions in least-squares mean change from baseline in PSD items related to itching/pain/scaling (–10.9 vs –5.8; P<0.0001), Scalpdex score (–23.4 vs –12.8; P<0.0001), and DLQI (–4.4 vs –2.4; P<0.0001).

Conclusion: Roflumilast foam 0.3% improved quality of life, including patient reported itching, pain, and scaling, related to psoriasis of the scalp and body.

Sponsorship: Arcutis Biotherapeutics, Inc.

Bimekizumab Maintenance of Response at Every Visit Over 4 Years in Patients with Psoriasis Achieving Clear Skin at Week 16: Results from Four Phase 3 Trials

Mark Lebwohl — 2025-03-17

Introduction: Achieving and maintaining skin clearance is key for patients with psoriasis.^1,2 However, loss of disease control over time is often seen with biologics; therefore, evaluating whether high efficacy levels are maintained at every visit in the long term is important.³ Here, we assess whether bimekizumab (BKZ)-treated patients, who achieved complete skin clearance (PASI 100; 100% improvement in Psoriasis Area and Severity Index) after 16 weeks, maintained BSA (body surface area) ≤1% and PASI 90/75 (≥90/75% improvement in PASI) responses at every visit over 4 years.

Procedure/study: Data were pooled from the 52/56-week BE VIVID/BE SURE/BE READY trials and their 144-week open-label extension (OLE) BE BRIGHT.^4–7 Included patients received BKZ 320 mg every 4 weeks (Q4W) to Week16, then Q4W or Q8W into the OLE; all received BKZ Q8W from Week100/104 or next scheduled visit. Dose groups were pooled for all analyses. Proportions of patients achieving PASI 100 at Week16 who maintained BSA ≤1%/PASI 90/PASI 75 at every subsequent study visit (29/30 further visits [study-dependent]) up to Year4 (Week196/200) are reported. Proportions who maintained their response at every visit except at most 1 and at most 2 are also reported. Patients discontinuing treatment due to lack of efficacy/treatment-related adverse events were considered non-responders at subsequent timepoints; last observation carried forward was used for other missing data (mNRI-LOCF).

Results: Of 989 BKZ-randomized patients, 62.7% achieved PASI 100 at Week16 (non-responder imputation). 503 Week16 PASI 100 responders received continuous BKZ and entered the OLE. Among these patients, BSA ≤1%, PASI 90, and PASI 75 responses were maintained at every study visit from Week16–Year4 by 69.4%, 80.9%, and 93.0% of patients, respectively (at every visit except at most 1: 79.5%, 87.5%, and 95.2%; at every visit except at most 2: 84.1%, 91.8%, and 96.8%).

Conclusion: High proportions of Week16 PASI 100 responders maintained BSA ≤1%/PASI 90/PASI 75 at every visit through 4 years. The vast majority maintained these responses at every visit except at most 2 visits through 4 years.

Funding: UCB. Medical writing support: Costello Medical.

Characterization of ORKA-001, a Novel Extended Half-life Monoclonal Antibody Targeting IL-23 for the Treatment of Psoriasis

Eugenia Levi — 2025-03-17

Introduction & Objectives:

Interleukin 23 (IL-23) is a proinflammatory cytokine that helps to maintain and activate T helper 17 (Th17) cells, the primary pathogenic cells in psoriasis. IL-23 plays a key role in the pathogenesis of psoriasis, as indicated by the association between the disease and mutations in components of the IL-23 signaling pathway, such as IL23R. Antagonism of the p19 subunit of IL-23 (IL-23p19) has proven to have robust efficacy and a favorable safety profile in the treatment of psoriasis.

ORKA-001 is a novel, extended half-life, humanized IgG1 monoclonal antibody that binds IL-23p19. ORKA-001 has been engineered to have optimized properties with the aim of delivering an enhanced clinical profile compared to current treatments for psoriasis.

Materials & Methods:

ORKA-001 was evaluated in multiple in vitro and ex vivo assays in comparison to two benchmark antibodies that target IL-23p19: risankizumab (RIS) and guselkumab (GUS). Binding affinity to IL-23 was determined by surface plasmon resonance (SPR). Antagonism of human IL-23 signaling was evaluated via assays measuring STAT3 activity in cell lines. Inhibition of IL-23-induced IL-17 secretion was assessed using in vitro cellular assays, including in human peripheral blood mononuclear cells (PBMC). Half-life extension was measured via pharmacokinetic (PK) analysis in cynomolgus monkeys dosed with a single bolus of ORKA-001.

Results:

ORKA-001 binds specifically to human IL-23 with an affinity below 20pM. It potently inhibits STAT3 activity in cell lines and IL-17 secretion in IL-23-stimulated human PBMC. IL-23 binding affinity and functional potencies for IL-23 antagonism are comparable to or better than those of RIS and GUS. The half-life of ORKA-001 is significantly extended in cynomolgus monkeys compared to both RIS and GUS. Based on allometric scaling of the clearance of ORKA-001 observed in this study, predictive simulations of ORKA-001 PK in humans suggest that subcutaneous maintenance dosing every six to twelve months could be achieved while maintaining high antibody exposures.

Conclusion:

ORKA-001 exhibits high selectivity and affinity for IL-23 in vitro, potent inhibition of downstream cellular signaling ex vivo, and an extended half-life in non-human primates compared to RIS and GUS. Both affinity and antibody exposure have been shown to have a positive correlation with efficacy in psoriasis, and ORKA-001 has the potential to exceed RIS and GUS on both metrics while requiring significantly fewer doses per year. In total, these data provide preclinical evidence of ORKA-001's clinical potential to improve upon currently available therapies for psoriasis. Clinical studies are warranted to demonstrate this potential.

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Linase 2 (TYK2) Inhibitor, in Patients with Moderate to Severe Scalp Psoriasis: The Association Between Patient-Reported and Clinician-Reported Outcomes at Week 16 in a Phase 3b/4 Multicenter, Randomized, Double-blinded, Placebo-controlled Study (PSORIATYK SCALP)

Steven R. Feldman — 2025-03-17

Introduction: In the phase 3b/4 PSORIATYK SCALP trial, deucravacitinib achieved superiority vs placebo for the primary and all key secondary endpoints at Week 16 in patients with moderate to severe scalp psoriasis. Patient-reported outcomes (PROs) provide additional information on treatment efficacy by capturing patients’ experiences and impact on their quality of life (QoL). This analysis evaluated the association between PROs and clinician-reported outcomes (CROs) in patients treated with deucravacitinib vs placebo.

Methods: This ad hoc analysis evaluated the associations between PROs (scalp-specific itch, pain, and flaking numeric rating scale [NRS], Scalpdex, and Dermatology Life Quality Index [DLQI]) and CROs (scalp-specific Physician Global Assessment [ss-PGA] and Psoriasis Scalp Severity Index [PSSI]) using Spearman’s correlation coefficients for absolute scores at baseline and Week 16. Descriptive analyses of PRO changes from baseline and response rates by CRO response groups were also calculated for deucravacitinib-treated patients.

Results: Baseline severity, scalp-specific symptoms, and QoL were similar between treatment groups, yet correlations were weak between PRO and CRO absolute values. At Week 16, correlations between PROs and CROs were stronger in deucravacitinib-treated patients vs placebo. The strongest correlations in deucravacitinib-treated patients were for itch and flaking NRS and Scalpdex symptoms (≥0.6; P<0.0001). QoL was moderately correlated with CROs (<0.6; P<0.0001) in deucravacitinib-treated patients. At Week 16, clinically meaningful improvements in scalp-specific itch, pain, and flaking and DLQI were reported by 76.2%, 89.5%, 88.4%, and 82.6% of patients who achieved ss-PGA 0/1 and by 72.7%, 66.7%, 91.7%, and 83.3% of those achieving PSSI 90, respectively. A 20-point reduction in Scalpdex total score was also reported by 75.6% and 66.7% of deucravacitinib-treated patients who achieved ss-PGA 0/1 and PSSI 90, respectively.

Conclusion: In deucravacitinib-treated patients, there was a strong correlation between patient-reported scalp symptoms and scalp-specific CROs, confirming the treatment benefit from the patient perspective. Moderate QoL/scalp-specific CRO correlations indicate that PROs provide complementary information about treatment benefits.

Impact of GPP on Quality of Life and Psychological Well-being: Results from a Non-interventional Survey/Interview-based Study

Mark G. Lebwohl — 2025-03-17

Generalized pustular psoriasis (GPP) is a rare, chronic, systemic inflammatory disease with a heterogeneous clinical course. GPP imposes a substantial emotional burden on patients, including feelings of fear and anxiety.¹

A post hoc analysis of a cross-sectional study was conducted via a web-based survey and qualitative telephone interviews with adults with GPP from China, Japan, the UK and USA. Those who completed the survey could choose to participate in the interview.

Twenty-one participants with GPP (mean age: 41 years; female: 57.1%) completed the survey; 9/21 participants (female: 55.6%) completed the interview. In total, 5/8 (62.5%) interview participants who were asked about GPP diagnosis expressed concerns, including lack of cure and risk of disease recurrence (n=1 for each). Other concerns at diagnosis included the long time to diagnosis (n=3), financial burden, and potential impact on their future children (n=1 for each). All participants reported an impact on their emotional well-being, either in general (n=8/9) or specifically due to flares (n=5/9). Two participants expressed fear and distress when they noticed signs of an impending flare,fear of others noticing their symptoms. Overall, 7/9 (77.8%) reported an impact on their social life, either in general (5/9) or due to flares specifically (5/9). This manifested most commonly (reported by 60–80% of participants) in the form of limited social activities/isolation due to their own or others’ negative feelings towards their skin’s appearance. All interview participants were receiving treatments, including systemic non-biologics, biologics and/or emollients, and 77.8% (7/9) reported treatment side effects. One third of participants expressed concerns about the potential consequences of treatment, including side effects and the risk of contracting other illnesses due to immunosuppression, indicating the need for educational materials (patients were receiving biologics [n=2] and systemic non-biologic [n=1]). One participant expressed fear that their current treatment was ineffective. When asked about their biggest worry, participants gave a variety of responses (n=5/9; 55.6%), including disease recurrence, distress related to symptoms and appearance of skin, passing GPP to their children, pain, and suboptimal treatment (all n=1).

Participants reported feelings of fear and related negative emotions throughout the disease course of GPP, and specifically due to flares.

Funding

This study was supported and funded by Boehringer Ingelheim.

Real-world Experience with Spesolimab in Chinese Patients with GPP

Min Zheng — 2025-03-17

Generalized pustular psoriasis (GPP) is a heterogeneous, neutrophilic inflammatory disease associated with chronic skin and systemic symptoms, and potentially life-threatening flares. We present safety and efficacy data from a real-world expanded access program (EAP) in China (12 sites; May 2022–July 2023), which provided early access to spesolimab (an anti-interleukin-36 receptor antibody) for patients not eligible for clinical trials and with no alternative treatment. Spesolimab was later approved in China for the treatment of GPP flares in adults (intravenous [IV] formulation [December 2022])¹ and the reduction of occurrence of GPP flare in adolescents from 12 years of age with a body weight of ≥40kg and adults (subcutaneous formulation [March 2024]).²

Patients received a 900mg dose of spesolimab IV for flare treatment (optional second dose after 1 week for persistent flare symptoms). Treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) were recorded up to Week 16 after the last spesolimab dose. Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore (PS) and total score (TS) were recorded at baseline and Week 1.

Thirty-nine patients (female, n=23) entered the EAP; 12 patients had available GPPGA scores at baseline (PS: 1, n=2; 2, n=2; 3, n=5; 4, n=3; TS: 2, n=4; 3, n=6; 4, n=2). Mean patient age: 39 years (range: 18–65); mean body mass index: 22.9kg/m². Flare triggers: treatment withdrawal (n=4), pregnancy (n=2), infection (n=1), other (n=7), and unknown (n=25). Thirty-six patients had ≥1 comorbidity and received ≥1 concomitant medication, including immunosuppressants, corticosteroids, topicals, and biologic therapies. Thirty patients (77%) experienced TEAEs, mostly mild/moderate (n=26). One patient had pneumonia and COVID-19 (SAE, AESI), one patient had pneumonia (SAE, AESI) and respiratory failure (SAE), and one patient had worsening of GPP (SAE). No AEs led to discontinuation/death. At Week 1, 9/12 patients (75%) had no pustules (GPPGA PS=0); the other 3 patients had a GPPGA PS of 1 or 2. Six of 12 patients (50%) had a GPPGA TS of 0/1 at Week 1 (clear/almost clear skin).

Spesolimab was well tolerated in Chinese patients with GPP, including those with a GPPGA TS of 2, a population not included in EFFISAYIL 1.³ Most patients (75%) demonstrated pustular clearance and AEs were consistent with the context of the EAP (COVID-19 pandemic) and comparable to those in the EFFISAYIL 1 trial.³

Funding: Study supported/funded by Boehringer Ingelheim.

Long-Term Effectiveness of Guselkumab vs. Other Biologic Therapies Among Plaque Psoriasis Patients in the CorEvitas Psoriasis Registry

Bruce Strober — 2025-03-17

Introduction: The efficacy and real-world treatment persistence of guselkumab (GUS) has been shown to be superior to other advanced treatment options [1,2] for psoriasis (PsO); however, long-term real-world effectiveness vs. other biologic therapies warrants further study. Therefore, this study compared the real-world effectiveness of GUS with adalimumab (ADA), ixekizumab (IXE), secukinumab (SEC), and ustekinumab (UST) in PsO patients through 30 months of follow-up.

Methods: An active comparator, new-user design was used to compare initiators of GUS to each comparator separately among adult patients with plaque PsO, an Investigator’s Global Assessment (IGA) score ≥2, and at least 30 months of follow-up prior to the data cutoff (June 2024) enrolled in the CorEvitas Psoriasis Registry in the US and Canada. Stabilized standardized mortality ratio (SMR) weights were used to balance baseline characteristics between GUS and each comparator. The primary outcome was achievement of IGA 0/1 at 30 months. Dermatology Life Quality Index (DLQI) 0/1 was assessed as a secondary outcome. Absolute differences were reported after incorporating the SMR weights. For all comparisons, P<0.05 was considered statistically significant and Bonferroni-Holm adjustments were made for multiple testing.

Results: After balancing on baseline characteristics, significantly greater proportions of GUS initiators achieved IGA 0/1 vs. those in each comparator group (GUS 50.7% (n=428) vs. ADA 24.0% (n=309): difference=26.7%, 95% CI: 13.6-39.7; p<0.001; GUS 43.4% (n=587) vs. IXE 33.6% (n=580): difference=9.9%, 95% CI: 2.6-17.1; p=0.005; GUS 45.8% (n=546) vs. SEC 29.9% (n=614): difference=15.9%, 95% CI: 6.8-25.0; p<0.001; GUS 45.9% (n=466) vs. UST 36.2% (n=224): difference=9.7%, 95% CI: 0.6-18.7; p=0.036). Similarly, greater proportions of GUS initiators achieved DLQI 0/1 vs. the comparators.

Conclusion: Our findings suggest that GUS was superior to ADA, IXE, SEC, and UST in achieving both IGA 0/1 and DLQI 0/1 at 30 months. This is among the largest and longest real-world comparative effectiveness studies of GUS vs. ADA, IXE, SEC, and UST in PsO patients. Additional studies with longer follow-up and inclusion of emerging therapies could provide further data to inform clinical treatment considerations.

Deucravacitinib in Moderate to Severe Plaque Psoriasis: 5-year, Long-term Safety and Efficacy Results from the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

April W. Armstrong — 2025-03-17

Introduction: Oral, targeted therapies for plaque psoriasis with long-term efficacy and safety are needed. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (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 efficacious and well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials. Here, we report deucravacitinib safety and efficacy through 5 years (Week 256; cutoff date, 9/2/2024).

Methods: Patients were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. After Week 52, patients enrolled in the POETYK long-term extension (LTE) (NCT04036435) trial received open-label deucravacitinib 6 mg once daily. Safety was evaluated in patients (n=1519) receiving ≥1 deucravacitinib dose through 5 years in the POETYK PSO-1, PSO-2, or LTE trials. Exposure-adjusted incidence rate per 100 person-years was used to assess adverse events. Efficacy was analyzed using modified nonresponder imputation in patients who received continuous deucravacitinib from Day 1 of the parent trials and were enrolled and treated in the LTE. Outcomes included PASI 75/90 and sPGA 0/1.

Results: Deucravacitinib was well tolerated with no new safety signals. In patients receiving continuous deucravacitinib as described above (n=513), high clinical response rates were generally maintained from Year 1 (PASI 75, 72.1% [95% CI, 68.2%-76.1%]; PASI 90, 45.9% [95% CI, 41.5%-50.4%]; sPGA 0/1, 57.5% [95% CI, 53.1%-61.9%]) to Year 5 (PASI 75, 67.3% [95% CI, 62.0%-72.6%]; PASI 90, 46.3% [95% CI, 41.2%-51.5%]; sPGA 0/1, 52.6% [95% CI, 47.0%-58.1%]).

Conclusion: Deucravacitinib demonstrated a consistent safety profile through 5 years with no emergence of any new safety signals. Clinical efficacy rates were maintained through 5 years of continuous treatment with once-daily oral deucravacitinib. These data support the long-term safety and durable efficacy profile through 5 years of treatment with deucravacitinib, a first-in-class TYK2 inhibitor treatment for psoriasis.

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 (TYK2) Inhibitor, in Patients with Moderate to Severe Scalp Psoriasis: Time to Meaningful Improvement in Patient-Reported Outcomes in a Phase 3b/4, Multicenter, Randomized, Double-blinded, Placebo-Controlled Study (PSORIATYK SCALP)

Linda Stein Gold — 2025-03-17

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. In the phase 3b/4 PSORIATYK SCALP trial, deucravacitinib was superior to placebo at Week 16 in patients with moderate to severe scalp psoriasis, including those with less extensive overall psoriasis (total body surface area [BSA] involvement ≥3%). This analysis evaluates the time to meaningful improvement in patient-reported outcomes (PROs) in patients treated with deucravacitinib vs placebo in the PSORIATYK SCALP trial.

Methods: Patients aged ≥18 years with moderate to severe scalp psoriasis were randomized 1:2 to once-daily placebo or deucravacitinib 6 mg. Evaluated PROs included scalp-specific itch, pain and flaking, and whole-body itch numeric rating scales (NRS), Scalpdex, and Dermatology Life Quality Index (DLQI). Times to meaningful improvement in these PROs (≥4-points reduction from baseline for NRS measures and DLQI; ≥20-point reduction for Scalpdex) were estimated using Kaplan-Meier methods. Cox regression models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) for response up to 16 weeks. Results are reported for the overall population and for subgroups of patients with baseline BSA 3%–10% and BSA >10% at baseline.

Results: In the overall population (placebo: n = 51; deucravacitinib: n = 103), patients treated with deucravacitinib had a shorter median time to meaningful improvement and were significantly more likely to achieve response by Week 16 for all PROs compared with patients receiving placebo (P < 0.05). In patients treated with deucravacitinib, the median time (95% CI) to meaningful improvement was 9.0 (8.0, 16.3), 8.7 (2.6, 15.7), 8.0 (4.1, 8.1), 8.3 (4.1, 15.7), and 2.1 (1.4, 4.3) weeks for scalp-specific itch, pain, and flaking NRS, whole-body itch NRS, and DLQI, respectively. The median time to meaningful improvement was also shorter with deucravacitinib vs placebo for all PROs in both the BSA 3%–10% and BSA <10% subgroups.

Conclusion: Deucravacitinib was associated with a shorter time to meaningful improvement vs placebo across evaluated PROs in the overall population and in BSA subgroups.

Deucravacitinib in Plaque Psoriasis: Immune Response to and Safety of Pneumococcus and Tetanus Toxoid Vaccines in the POETYK LTE Trial

Joanna Narbutt — 2025-03-17

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 safety and efficacy were maintained through 4 years in the phase 3 POETYK long-term extension (LTE) (NCT04036435) trial. The effect of deucravacitinib treatment on immune response to vaccines has not been evaluated. This POETYK LTE substudy evaluated immune response to and safety of non-live pneumococcus (T-cell independent) and tetanus toxoid (T-cell dependent) vaccines in patients receiving continuous deucravacitinib.

Methods: Patients were required to have received open-label deucravacitinib 6 mg once daily for ≥1 year in POETYK LTE prior to the vaccine substudy. Patients were randomized 1:1 to blinded deucravacitinib or placebo on Day 1 through Day 36 to assess immune response to vaccination. Pre-vaccination serum titers, vaccinations, and safety assessments were performed on Day 8, vaccine-related safety assessments were performed remotely on Day 18, and post-vaccination titers and safety assessments were performed on Day 36. Primary endpoint was serologic response to 23-valent pneumococcal vaccine (PPSV-23) and tetanus toxoid vaccine (TTV) on Day 36. Secondary endpoints included seroprotection and seroconversion in tetanus toxoid-specific antibody titers, immune response measured by antibody titers and opsonophagocytic activity, and safety.

Results: Baseline patient demographics and clinical characteristics were similar across groups (deucravacitinib, n=28; placebo, n=25). Proportions of patients achieving serologic response criteria to PPSV-23 (deucravacitinib, 85.7% vs placebo, 100.0%; difference [95% CI], -14.3% [-31.5%, 1.6%]) and TTV (deucravacitinib, 64.3% vs placebo, 80.0%; -15.7% [-37.3%, 8.6%]) were high in the deucravacitinib group and numerically lower than in the placebo group. Tetanus toxoid seroprotection (100.0% vs 100.0%; 0.0% [-12.1%, 13.3%]) was achieved by all patients. Seroconversion (64.3% vs 76.0%; -11.7% [-34.0%, 12.8%]) was numerically lower with deucravacitinib versus placebo, respectively. After adjusting for baseline titers, PPSV-23 and TTV mean titers at Day 36 were generally similar across both treatment groups. Opsonophagocytic activity for pneumococcus serotypes was comparable in both groups at Day 36. Adverse events (AEs) were infrequent and comparable across groups; no severe or serious AEs were reported. No clinically meaningful changes in laboratory parameters related to study treatment were observed.

Conclusion: In patients with plaque psoriasis, continuing deucravacitinib treatment did not impact humoral responses to the PPSV-23 (T-cell independent) and TTV (T-cell dependent) vaccines. Our data suggest that withholding deucravacitinib treatment at the time of these vaccinations is not required.

Impact of Deucravacitinib on Psoriasis Severity and Overall Patient-reported Outcomes in a US Prospective Cohort Study

Alexis Ogdie — 2025-03-17

Background: Deucravacitinib is the first oral tyrosine kinase 2 inhibitor approved by the US Food and Drug Administration (FDA) for moderate-to-severe plaque psoriasis (PsO). Phase 2 and Phase 3 clinical trials have shown clinical efficacy across various endpoints. Long-term clinical trial data of deucravacitinib in moderate-to-severe plaque PsO also show that treatment efficacy is durable. However, real-world evidence regarding the patient-reported outcomes (PROs) of patients treated with deucravacitinib for PsO is limited.

Objective: The goal of this PRO study is to understand the impact of deucravacitinib on improvement of PsO signs and symptoms.

Methods: Patients were recruited from U.S dermatology offices as a part of a national practice group, through a patient support program for deucravacitinib, and online from the FORWARD registry website. Patients were enrolled between August 2023 and November 2024. Inclusion criteria were adult patients initiating deucravacitinib ≤14 days of survey enrollment. We descriptively report demographics, disease characteristics, current treatments, and comorbidities for participants at enrollment as well as mean change in key PROs and patient-reported psoriasis severity at 6 months among the subset of patients who were persistent on deucravacitinib at 6 months. Psoriasis Symptoms and Signs Diary (PSSD) score was the primary outcome (range 0-100), and a meaningful change was set to be at least 15 point improvement. [Papp JAMA Dermatol 2023]

Results: Among 306 patients with PsO initiating deucravacitinib, 81 (20.9%) had completed a 6-month follow up. Among these, 51 (63.0%) were persistent on therapy. Baseline demographics for these 51 persistent patients did not differ substantially from the overall cohort of initiators. The mean baseline PSSD was 32.2 (SD: 24) and change from baseline to 6 months was -19.0, which is above the set point for meaningful change. For overall global assessment of psoriasis severity (range 0-100), baseline was 42.7 (SD: 28.7), and average change from baseline was -25.3 (SD: 27.4). Dermatology Life Quality Index (DLQI) was 8.5 (SD: 4.7) at baseline and changed -4.3 (5.4). The global assessment of itch (numeric rating score) was 4.3 (SD 3.0) at baseline and changed -2.7 (3.2). For patient global assessment of nail disease (range 0-100), baseline was 25.6 (SD: 31.9), and changed -10.2 (SD: 25.8). Body surface area of psoriasis improved as well. At baseline 5.9% had a BSA<1% whereas at 6 months, 45.1% achieved BSA <1%. Treatment satisfaction also improved with 69% indicating they were satisfied or highly satisfied at follow up on deucravacitinib, compared with 33% at baseline.

Conclusions: Deucravacitinib was associated with improvements in psoriasis severity and patient-reported outcomes in a real-world setting.

Impact of Deucravacitinib on Scalp Psoriasis in a Real-world Prospective Cohort Study in the United States

Alexis Ogdie — 2025-03-17

Background: Real-world data indicate that patients with psoriasis (PsO) affecting the scalp, nails, palms, soles, and genitals report worse patient-reported outcomes (PROs) than those without PsO involvement in these special areas, despite having the same level of disease severity. Deucravacitinib is the first oral tyrosine kinase 2 inhibitor approved by the US Food and Drug Administration (FDA) for moderate-to-severe plaque psoriasis. Phase IV scalp-specific clinical trials have shown that deucravacitinib was efficacious across multiple efficacy endpoints. However, real-world evidence is limited for patients with psoriasis in difficult-to-treat areas, such as the scalp.

Objective: The goal of this PRO study is to understand the impact of deucravacitinib on improvement of PsO signs and symptoms among patients with scalp PsO in the real world.

Methods: Patients were recruited from dermatology offices of a U.S practice group, through a patient support program for deucravacitinib, and online from the FORWARD registry website. Patients were enrolled between August 2023 and November 2024. Inclusion criteria were adult patients initiating deucravacitinib ≤14 days of survey enrollment and continuation of deucravacitinib at 6-month follow up. We descriptively report demographics, disease characteristics, and comorbidities for participants at enrollment as well as mean change in key PROs and patient-reported psoriasis severity at 6 months in the subset of patients with scalp psoriasis. Psoriasis Symptoms and Signs Diary (PSSD) score was the primary outcome (range 0-100). All patients also completed a Dermatology Life Quality Index (DLQI) and patients with scalp PsO completed scalp-specific questions including the Scalp Specific Itch (SS-itch) numeric rating scale (NRS), scalp specific pain (SS-pain) NRS, and the scalp specific flaking (SS-flaking, NRS).

Results: Among 306 patients with psoriasis initiating deucravacitinib, 219 (71.6%) reported scalp psoriasis. Of these, sixty patients (27.4%) completed a 6-month follow up, and 39 of these (65.0%) were persistent on therapy at 6 months. At baseline, the mean PSSD was higher among those with scalp psoriasis compared to those without reported scalp psoriasis (34.1 vs 25.8). At 6-month follow up, the mean change in PSSD among those with scalp psoriasis was -19.2 (SD: 27.6). Mean DLQI at enrollment among those with scalp psoriasis was 8.5 (SD: 4.7) and change in DLQI at 6 month follow up was -4.5 (SD: 5.4). Scalp itch (0-10) at baseline was 4.1 (SD: 3.0) and mean change was -1.9 (SD: 2.7). Mean scalp flaking (0-10) at baseline was 4.7 (SD: 3.0) and mean change was -2.0 (SD: 3.2). Mean scalp pain at baseline was 1.8 (SD: 2.8) and mean change was -0.3 (SD: 2.2).

Conclusions: Deucravacitinib was associated with improvements in scalp psoriasis and patient-reported outcomes of disease impact and quality of life in a real-world setting.

Efficacy of Deucravacitinib over time in Psoriasis by Baseline Total Body Surface Area: Post Hoc Analysis of the Randomized, Double-blind, Placebo-controlled Phase 3b/4 PSORIATYK SCALP Trial

Christopher E.M. Griffiths — 2025-03-17

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. In the phase 3b/4 PSORIATYK SCALP (NCT05478499) trial, deucravacitinib was superior to placebo at Week 16 in patients with moderate to severe scalp psoriasis, including those with more limited overall psoriasis. Here, we report efficacy of deucravacitinib in improving overall body psoriasis in patients with baseline total body surface area (BSA) involvement ≥3%, 3%-10%, and >10%.

Methods: Outcomes were analyzed by baseline BSA involvement (BSA ≥3%, all randomized patients; BSA 3%-10% and BSA >10%, BSA-defined subgroups) through Week 16 and included static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1), ≥75%/≥90% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75/90), and adjusted mean percent change from baseline BSA. Analyses are post hoc; P values were obtained using a stratified Cochran-Mantel-Haenszel test, unstratified chi-squared test, or an analysis of covariance; all P values are nominal.

Results: Overall (BSA ≥3%), 103 patients were assigned to deucravacitinib and 51 to placebo (n=70 vs n=38 [BSA 3%-10%] and n=33 vs n=13 [BSA >10%] for deucravacitinib versus placebo, respectively). Week 16 sPGA 0/1 response rates were higher for patients treated with deucravacitinib versus placebo overall (47.6% vs 3.9%; BSA ≥3%) and by BSA subgroups (42.9% vs 5.3% [BSA 3%-10%] and 57.6% vs 0% [BSA >10%]; all P<0.001). Week 16 PASI 75 response rates were also higher for patients treated with deucravacitinib versus placebo overall (42.7% vs 5.9% [BSA ≥3%]) and by BSA subgroups (34.3% vs 7.9% [BSA 3%-10%] and 60.6% vs 0% [BSA >10%]; all P<0.01). PASI 90 outcomes showed similar trends for deucravacitinib versus placebo. Patients treated with deucravacitinib had greater adjusted mean percent change from baseline in BSA score versus placebo overall (−43.4% vs +4.8% [BSA ≥3%]) and by BSA subgroups (−32.6% vs +3.4% [BSA 3%-10%] and −69.3% vs +9.5% [BSA >10%]; all P<0.05).

Conclusion: In PSORIATYK SCALP, deucravacitinib improved overall psoriasis through Week 16 compared with placebo in patients with more limited overall psoriasis (BSA ≥3%) and in both subgroups (BSA 3%-10%, BSA >10%).

Deucravacitinib in Psoriasis Patients with a History of Malignancy: Follow-up after 4 Years of Deucravacitinib Treatment in the POETYK PSO Program

Mark Lebwohl — 2025-03-17

Introduction: The global phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) trials of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, included psoriasis patients with a history of malignancy. This descriptive analysis evaluated malignancy events in deucravacitinib-treated patients with malignancy prior to enrolling in the POETYK PSO-1, PSO-2, and long-term extension (NCT04036435) trials.

Methods: Patients in the pooled population who received ≥1 dose of deucravacitinib at any time over 4 years (data cutoff, November 1, 2023) were screened to identify those with a history of malignancy at baseline with no evidence of recurrence for >5 years prior to enrollment. Baseline patient demographics and clinical characteristics, type of prior malignancy, total deucravacitinib exposure, deucravacitinib treatment discontinuation, and occurrence of malignancy were evaluated for each patient with a history of malignancy.

Results: Among 1519 deucravacitinib-treated patients, 19 had a history of malignancy (12 had a history of malignancy excluding nonmelanoma skin cancer [NMSC]; 7 had NMSC). Patients with a history of malignancy were older (mean age, 64.3 vs 46.6 years), had longer disease duration (mean, 36.2 vs 18.7 years), and had shorter deucravacitinib exposure (median, 814 vs 1298 days) compared with the total pooled population. Six of the 12 (50.0%) patients with a history of malignancy excluding NMSC discontinued treatment due to patient withdrawal (n=2), occurrence of malignancy (n=1), adverse events (n=1), lost to follow-up (n=1), or study site termination (n=1). Among the 12 patients with a history of malignancy excluding NMSC, there was 1 occurrence of malignancy.

Conclusion: Malignancies were infrequently observed with deucravacitinib treatment in psoriasis patients with a history of malignancy. Analysis of larger patient populations over a longer duration of follow-up using real-world data will help to further characterize the safety of deucravacitinib in psoriasis patients with a history of malignancy.

Onset of Clinical Response with Deucravacitinib in Patients with Moderate to Severe Scalp Psoriasis: A Post Hoc Analysis of the Phase 3b/4 PSORIATYK SCALP Trial

Matthias Hoffmann — 2025-03-17

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved in the US and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. In the phase 3b/4 PSORIATYK SCALP (NCT05478499) trial, deucravacitinib was superior to placebo at Week 16 in patients with moderate to severe scalp psoriasis, including those with more limited overall psoriasis. Here, we report a post hoc analysis evaluating the onset of clinical response in the overall population and in patient subgroups based on body surface area (BSA) involvement.

Methods: Outcomes were scalp-specific Physician Global Assessment score of 0 (clear) or 1 (almost clear) (ss-PGA 0/1), ≥75%/≥90%/100% reduction from baseline in Psoriasis Scalp Severity Index (PSSI 75/90/100), adjusted mean change and adjusted percent change from baseline in PSSI, and mean change and percent change from baseline in scalp surface area involvement. Outcomes were evaluated through Week 16 in all randomized patients (BSA involvement ≥3%), patients with BSA involvement 3%-10%, and patients with BSA involvement >10%. P values were obtained using a stratified Cochran-Mantel-Haenszel test, unstratified chi-squared test, or an analysis of covariance; all P values were nominal.

Results: ss-PGA 0/1 response rates were significantly higher for deucravacitinib versus placebo by Week 4 in the overall population (11.7% vs 0.0%, P=0.01; n=103 vs 51); ss-PGA 0/1 response rates were higher for deucravacitinib by Week 4 in the BSA 3%-10% subgroup (11.4% vs 0.0%, P=0.03; n=70 vs 38) and by Week 8 in the BSA >10% subgroup (51.5% vs 0.0%, P=0.001; n=33 vs 13). PSSI 90 response rates were also significantly higher for deucravacitinib by Week 8 (BSA ≥3%: 21.4% vs 2.0%, P=0.0016; BSA 3%-10%: 15.7% vs 2.6%, P=0.0388; BSA >10%: 33.3% vs 0.0%, P=0.0170). Adjusted mean percent change from baseline in PSSI total score was significantly greater with deucravacitinib by Week 4 (BSA ≥3%: −40.2% vs −13.8%, P<0.0001; BSA 3%-10%: −35.3% vs −17.0%, P=0.0087; BSA >10%: −51.8% vs −6.8%, P=0.0004). Similar trends were observed for the other efficacy outcomes. Improvements with deucravacitinib continued for all outcomes through Week 16.

Conclusion: In PSORIATYK SCALP, deucravacitinib demonstrated significant improvement in scalp-specific efficacy outcomes as early as Week 4, including in patients with more limited overall psoriasis. Improvements continued through Week 16.

Generalized Pustular Psoriasis (GPP) Control is Limited on Traditional Small-molecule Therapy as Measured by the GPP Physician Global Assessment (GPPGA) and Dermatology Life Quality Index (DLQI): Baseline Data from the EFFISAYIL® 2 Trial

Arash Mostaghimi — 2025-03-17

Introduction: GPP is a chronic inflammatory, potentially life-threatening skin disease. Most patients experience chronic skin symptoms between flares leading to significant patient burden. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved to treat GPP in adults and pediatric patients aged ≥12 years and weighing ≥40 kg. EFFISAYIL^® 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous (SC) spesolimab in GPP. Most patients entering the trial were receiving a traditional small-molecule therapy prior to randomization and all had a baseline GPPGA¹ total score of 0 or 1. Here, we report the GPPGA total score and DLQI score at baseline stratified by small-molecule medication received prior to randomization in EFFISAYIL^® 2.

Methods: Patients were stratified by baseline medication use, including medications received by ≥5 patients or no medication. GPPGA was assessed as the proportion of patients with a score of 1. For DLQI, mean and standard deviation (SD) were calculated.

Results: Despite treatment with traditional small-molecule therapies before entering EFFISAYIL^® 2, most patients in each baseline medication group did not have clear skin (GPPGA total score=1) and all groups reported poor quality of life (mean DLQI>5). These observations were consistent with findings among patients who did not receive small-molecule therapy before randomization. The respective proportion of patients with a GPPGA total score of 1 by each medication group was: 95.6% (n=43) for acitretin, 84% (n=21) for cyclosporine, 66.7% (n=10) for methotrexate, and 80% (n=4) for any 2 small molecules (i.e., acitretin, methotrexate, cyclosporine), compared with 87.1% (n=27) for those not receiving prior small-molecule therapy. The mean (SD) DLQI scores at baseline were: 8.3 (5.6) for acitretin (n=45), 7.7 (7.4) for cyclosporine (n=25); 9.9 (7.4) for methotrexate (n=15), and 5.4 (7.2) for 2 small molecules (n=5); compared with 8.1 (6.1) for no therapy.

Conclusion: Despite being treated with traditional small-molecule therapy before randomization, many patients entering EFFISAYIL^® 2 still demonstrated incomplete skin clearance, as shown by GPPGA total score and DLQI scores, reflecting a moderate effect on a patient’s life. These findings suggest that approved, targeted therapy should be considered to reduce the clinical burden of GPP.

The Chronicity and Disease Burden of Generalized Pustular Psoriasis

Thomas Selby — 2025-03-17

Introduction: Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by sudden, widespread eruption (flare) of small sterile pustules often with systemic symptoms. Many patients experience chronic symptoms between flares and may require continuous management.

Methods: We describe the long-term burden of GPP and its effects on quality of life (QoL) in 10 patients who presented to US clinical practices with GPP flare.

Results: Patients were aged 18–92 years with comorbidities (e.g., hypertension, plaque psoriasis, obesity, type 2 diabetes, hypercholesterolemia, diverticulitis, dementia, depression). At presentation, all patients had visible signs of GPP, plus pain, itch, or a sensation of heat in the skin; several experienced systemic symptoms, including leukemoid reaction, painful joints/muscles, fever, or altered mental status. Several patients presented to the emergency room; over half required hospitalization for management. Reported flare triggers included hydroxychloroquine treatment, corticosteroid withdrawal, stress, and COVID-19 infection, though for some, the trigger was unknown. All patients previously received multiple off-label medications for their GPP symptoms. GPP flare was initially misdiagnosed in 6 patients: acute generalized exanthematous pustulosis (2), guttate psoriasis, nummular dermatitis, rheumatoid arthritis and lupus, and contact dermatitis. All misdiagnosed cases received oral or topical corticosteroid treatment, which failed or worsened GPP flare and delayed initiation of targeted GPP treatment. Diagnosis of GPP was usually achieved via skin biopsy. All patients experienced chronic GPP symptoms requiring long-term management. Patients reported a continuous impact of GPP on QoL. One patient’s activities of daily living were severely affected, another reported joint and muscle pain prevented her from walking, and an 18-year-old patient reported being bullied because of his skin’s appearance. For 6 patients this was their first flare, while the others experienced flare recurrence. One patient had 1 previous flare and 3 patients had experienced multiple flares. One of these patients, now aged 62 years, had experienced numerous flares since childhood. GPP flares led to severe complications and morbidity in several patients, including multiple organ failure, fever, and altered mental status during the flare.

Conclusions: GPP is associated with both recurrent flares and chronic symptoms between flares, leading to decreased patient QoL, increased morbidity, and risk of complications. Thus, safe and effective long-term treatment options for GPP are needed to mitigate disease burden.

Treatment Outcomes and Management of Generalized Pustular Psoriasis with Spesolimab

Joe Tung — 2025-03-17

Introduction: Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease characterized by sudden, widespread eruption (flare) of sterile pustules often with systemic symptoms. Spesolimab is a humanized anti-IL-36 monoclonal antibody approved in the US to treat GPP in adults and adolescents ≥12 years and weighing ≥40 kg as an IV dosage to treat flares and a SC dosage to treat GPP when patients are not experiencing a flare.

Methods: We describe outcomes in 10 patients with GPP flare who received spesolimab at hospitals and clinics across the US.

Results: The 10 patients were aged 18–92 years (6 female); all had comorbidities (e.g., hypertension, diabetes). All 10 patients had GPP flare symptoms, including pustular rash and erythema, and received spesolimab via IV infusion. Two patients received spesolimab within ≤1 week of flare symptoms, while initiation of spesolimab was delayed in 8 patients (5 patients by 3–4 weeks, 3 patients by ≥4 months). Seven patients had significant skin improvement within ≤1 week after the first IV spesolimab dose. Overall, 8 patients received a second IV spesolimab dose 7–35 days after the first dose to facilitate further skin clearance. One patient had a further flare 4 months after the second dose and required a third IV spesolimab infusion. In all patients who had failed multiple other treatments previously (e.g., topical/oral corticosteroids and off-label biologics), spesolimab improved flare symptoms with no washout period needed. Notably, improvements were observed in a patient with high BMI, and a 92-year-old patient. Patients reported benefits in quality of life (QoL), with increased confidence, mood, and ability to carry out daily activities. One patient developed a diffuse herpes simplex virus type 1 infection following infusion, attributed to either spesolimab or concurrent cyclosporine, and another went into distributive shock, which was unrelated to spesolimab treatment. No other safety issues were identified as related to spesolimab treatment.

Conclusion: Access to targeted treatment is crucial to improve outcomes in patients experiencing GPP flare. These 10 cases demonstrate the safety and efficacy of spesolimab in providing rapid improvement in GPP symptoms and patient QoL in a real-world setting.

Multiple Congenital Hemangiomas

Christopher Chino-Marin — 2025-03-17

Intraumbilical Mass with Cyclical Drainage

Alexis Coican — 2025-03-17

Severe Bullous Hypersensitivity Reaction After Copperhead Snakebite and Antivenom Therapy

Isha Jhingan — 2025-03-17

Dermoscopy of Gouty Tophus: Unveiling New Patterns

Rasha Moumna — 2025-03-17

A Case of Primary Cutaneous CD4+ Small/Medium T-cell Lymphoproliferative Disorder

Dana Olsen — 2025-03-17

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-TCLPD) is a rare lymphoproliferative condition that typically manifests as a solitary, asymptomatic cutaneous nodule. Systemic involvement is uncommon, and diagnosis is confirmed via biopsy, which reveals a predominant population of CD4-positive T-cells with a follicular helper T-cell phenotype. Treatment generally involves conservative local approaches, including biopsy, topical steroids, or excision, with many cases demonstrating spontaneous regression after biopsy. This report presents the case of a 68-year-old woman with a 6.0 x 6.0 mm subcutaneous nodule on the left preauricular cheek. The lesion appeared over 4–5 weeks and was asymptomatic. Biopsy revealed a dense lymphohistiocytic infiltrate of predominantly CD4-positive T-cells, with clonality confirmed through molecular studies. Additional workup, including complete blood count, metabolic panel, and imaging, revealed no systemic involvement. Oncology recommended observation without further excision. At three months post-biopsy, the lesion had not recurred.

PCSM-TCLPD, which accounts for 5% of primary cutaneous lymphomas, was reclassified as a lymphoproliferative disorder by the World Health Organization in 2016 due to its indolent nature. While its prognosis is excellent, with a five-year survival rate near 100%, careful diagnostic and therapeutic strategies are critical. Spontaneous remission post-biopsy supports the role of conservative management, minimizing invasive interventions. This case underscores the importance of recognizing PCSM-TCLPD’s clinical and histopathological features to ensure accurate diagnosis and optimize patient outcomes while avoiding unnecessary procedures. Further research is needed to refine treatment and follow-up strategies for this rare condition.

Unveiling Multiple Chronic Relapsing Plaques and Ulcerations in a Healthy Individual

Nattanicha Chaisrimaneepan — 2025-03-17

Lupus erythematosus panniculitis is an uncommon variant of chronic cutaneous lupus erythematosus. The lesions are characterized by the involvement of subcutaneous tissue, typically presented with tender erythematous or purplish subcutaneous nodules or plaques with different overlying skin appearances, rarely skin ulceration. The clinical course of LEP is typically chronic and relapsing with periods of exacerbations which can be triggered by trauma. Most LEP patients have a favorable prognosis in SLE patients. We report a 60-year-old Southeast Asian female who presented with reddish ulcerated plaques on the face and left arm for 2 months. Histopathological findings showed peri-adnexal and subcutaneous fat lobule inflammation consisted of lymphocytes, plasma cells, and some histiocytes. Focal hyaline necrosis of fat cells was also identified. Although DIF tests showed negative results, CD123+ immunohistochemical staining was found positive. Other blood investigations were unremarkable. She did not fulfill the criteria for systemic lupus erythematosus. She was successfully treated with hydroxychloroquine, oral prednisolone, and a topical potent corticosteroid. The patient clinically improved within a few months with hyperpigmentation.

Trichoadenoma on the Dorsal Forearm

Rebecca Lapides — 2025-03-17

Trichoadenomas are benign adnexal tumors that originate from the pilosebaceous unit. They are typically observed on the head and buttock region. Here, we present a case of a trichoademona found on the dorsal forearm, which emphasizes the consideration of this diagnosis on the differential for cystic or nodular lesions, even when present on the distal extremities.

Successful Treatment of Terbinafine-Induced Subacute Cutaneous Lupus Erythematosus With Upadacitinib

Chloe H Franzia — 2025-03-17

Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is now the most common form of drug-induced lupus erythematosus (DI-LE). Terbinafine is a well-established DI-SCLE trigger and most cases resolve with traditional therapies, such as topical and oral steroids. However, some cases may be more persistent and refractory to these treatments, or patients may be unable to tolerate systemic steroid use due to underlying conditions. These challenges highlight the limitations of conventional therapies, underscoring the need for alternative treatments in difficult to treat or protracted cases. This report presents a case of terbinafine-induced SCLE that was unresponsive to systemic steroids and quickly resolved with a short course of upadacitinib, an oral selective JAK-1 inhibitor.

Cylindroma in a Young Woman with a Germline Checkpoint Kinase 2 Gene Mutation Case Report

Rebecca Rist — 2025-03-17

A cylindroma is a benign, slow-growing sweat gland neoplasm that tends to occur on the face or scalp. Cylindromas are often multiple in association with an underlying genetic abnormality such as the germline CYLD mutation seen in Brooke-Spiegler syndrome. Sporadic cylindromas are rare, tend to effect older individuals, and have been associated with MYB overexpression. We present a case report of a cylindroma developing in a young female patient with a known germline Checkpoint Kinase 2 (CHEK2) mutation. We hypothesize that her CHEK2 mutation resulted in cylindroma formation by way of CHEK2’s downstream effects on p53 and MYB.

A Verrucous Lesion on a Nose in HIV Seropositive Female: A Rare Case Report

Supriya Kachare — 2025-03-17

Tuberculosis is a chronic granulomatous infectious disease caused by mycobacterium tuberculosis and mycobacterium bovis. Although commonly affecting lungs, almost all other organ systems may be involved. Cutaneous tuberculosis is one of the most challenging diseases to diagnose. It possesses a wide array of differential diagnosis and is difficult to confirm microbiologically, often leading to delayed diagnosis and treatment. Emergence of resistant strains and the HIV pandemic contribute to distribution of cutaneous tuberculosis worldwide. Clinical findings of cutaneous tuberculosis depend on source of infection and immune status of host. We report an HIV seropositive female presenting with a verrucous fungating growth over nose, which was diagnosed as tuberculosis cutis orificialis likely due to endogenous seeding from pulmonary disease. She was treated with extended anti-tubercular therapy (HRZE) fixed dose combination. The lesion responded remarkably to treatment and resolved completely within 18 months.

A Granular Cell Tumor on the Finger of a 7-Year-Old Boy: A Case Report

Alberto Gómez Trigos — 2025-03-17

Granular cell tumor (GCT) is a rare neoplasm originating from Schwann cells and is classified into benign and malignant subtypes. This report presents the case of a 7-year-old boy with a GCT located on the third finger of his right hand. The lesion measured 1 cm × 1 cm and was characterized by a nodular appearance with a keratotic surface, well-defined borders, and a scaly collar at the base. Histopathological examination revealed the presence of large polyhedral cells with small, centrally located, hyperchromatic nuclei and cytoplasm filled with eosinophilic granules, consistent with a benign granular cell tumor. This case highlights the importance of thorough histopathological evaluation and interdisciplinary collaboration in the accurate diagnosis and management of GCT, particularly in pediatric patients and in atypical locations.

COVID-19 Vaccination as a Precipitating Factor in Cutaneous Lupus Erythematosus with Lupus Nephritis: A Clinical Case Report

Elisha Myers — 2025-03-17

The advent of the COVID-19 vaccine has improved global mortality, but recent literature suggests that COVID-19 vaccinations may induce or exacerbate autoimmune rheumatic diseases. Here, we present a 64-year-old woman with a history of Evans syndrome, pernicious anemia, and positive antinuclear antibody (ANA) who developed systemic lupus erythematosus (LE) presenting with cutaneous involvement following her first Moderna COVID-19 vaccine dose. She presented with a pruritic rash, malaise, and paresthesia ten days after vaccination. Clinical examination revealed erythematous, scaly, annular plaques on her face, ears, upper extremities, and chest, hand edema, and a palatal erosion. Laboratory findings included an elevated ANA titer (1:640), positive anti-RNP and anti-Ro antibodies, hematuria and proteinuria. This contrasted with previous laboratory results from 2019, where her ANA titer was higher at 1:2560, with anti-RNP elevated at 358 and anti-Ro at 252. Skin biopsy confirmed cutaneous LE and renal biopsy confirmed membranous lupus nephritis. Treatment included hydroxychloroquine, mycophenolate mofetil, prednisone, clobetasol ointment, and triamcinolone ointment, with subsequent improvement. Although rare, COVID-19 vaccination should be considered as a potential trigger for LE, particularly in patients with predisposition to autoimmune disease. Vaccination against COVID-19 should still be encouraged among patients with autoimmune rheumatic diseases, preferably during remission and before the initiation of disease-modifying antirheumatic drugs.

Multiple Basal Cell Carcinomas Mimicking Segmental Neurofibromatosis: A Clinical Conundrum

Helen Chen — 2025-03-17

Basal cell carcinomas (BCC) are the most common type of skin cancer, typically presented as pearly pink papules on areas of the body with chronic ultraviolet (UV) exposure. Sporadic segmental BCC has been rarely reported in the literature and can often be mistaken for other skin conditions, such as segmental neurofibromatosis or inherited segmental basal cell nevus syndrome. A comprehensive clinical history, a detailed physical examination with dermoscopy, and maintaining a high index of suspicion for biopsy allowed us to achieve an accurate diagnosis. Initiating targeted therapy with Vismodegib resulted in rapid clinic improvement and a significant enhancement in the patient’s quality of life.

Diagnostic Outcomes of Clinically Diagnosed Lichen Planus-Like Keratosis

Jordan Phillipps — 2025-03-17

Lichen planus-like keratosis (LPLK), also known as benign lichenoid keratosis (BLK), are pink/red-brown papules that are thought to represent regressing inflamed solar lentigo or seborrheic keratosis. Prior studies have evaluated the differential diagnosis before biopsy for histologically diagnosed LPLK/BLK; however, diagnostic outcomes and prevalence of malignancy in clinically appearing LPLK/BLK have not been reported. Here, we report a single-institution, retrospective chart review from 2013-2020 evaluating the prevalence of malignancy in a set of lesions clinically appearing as LPLK/BLK. The most common first differential diagnoses were BCC (42%) and LPLK/BLK (35%). The most common histologic diagnosis was BCC (28%), followed by LPLK/BLK (26%). Considering all lesions, 44% were diagnosed as malignant (28% BCC, 14% SCCIS, 1.4% melanoma) and 26% were diagnosed as LPLK/BLK. Conversely, considering lesions with LPLK/BLK first in the differential diagnosis, 33% had a malignant diagnosis (19% BCC, 13% SCCIS, 1% melanoma) and 36% had a diagnosis of LPLK/BLK. These results provide valuable insight into characterizing diagnostic outcomes and malignancy prevalence for clinically appearing LPLK/BLK to guide patient-centered shared decision-making.

Thiamidol (isobutylamido thiazolyl resorcinol): A Highly Specific Human Tyrosinase Inhibitor for the Treatment of Hyperpigmentation

Tobias Mann — 2025-03-17

Thiamidol (isobutylamido thiazolyl resorcinol): A Highly Specific Human Tyrosinase Inhibitor for the Treatment of Hyperpigmentation

Tobias Mann¹, Wolfram Gerwat¹, Jan Batzer¹, Kerstin Eggers¹, Cathrin Scherner¹, Horst Wenck¹, Franz Stab¹, Vincent J. Hearing², Klaus-Heinrich Rohm³, Ludger Kolbe¹

¹Front End Innovation, Beiersdorf AG, Hamburg, Germany; ²DASS Manuscript, Haymarket, Virginia, USA; ³Institute of Physiological Chemistry, Philipps University, Marburg, Germany

Tyrosinase is the rate-limiting enzyme of melanin production, and accordingly, is the most prominent target for inhibiting hyperpigmentation. Numerous tyrosinase inhibitors have previously been identified; however, most lack clinical efficacy because they were identified using mushroom tyrosinase as the target substrate. Therefore, we used recombinant human tyrosinase to screen a library of 50,000 compounds and compared the active screening hits with well-known anti-pigmentation ingredients, including 4-butylresorcinol, kojic acid, rhododendrol, hydroquinone, and arbutin. Hydroquinone and its derivative arbutin only weakly inhibited human tyrosinase with a half-maximal inhibitory concentration (IC₅₀) in the millimolar range, and kojic acid showed a weak efficacy (IC₅₀ > 500 mmol/L). The most potent inhibitors of human tyrosinase identified in this screening were resorcinol-thiazole derivatives, specifically the newly identified Thiamidol (Beiersdorf AG, Hamburg, Germany) (isobutylamido thiazolyl resorcinol), which had an IC₅₀ of 1.1 mmol/L. In contrast, Thiamidol only weakly inhibited mushroom tyrosinase (IC₅₀ = 108 mmol/L), demonstrating the specificity of inhibition for human tyrosinase. In melanocyte cultures, Thiamidol strongly, but reversibly, inhibited melanin production (IC₅₀ = 0.9 mmol/L), whereas hydroquinone irreversibly inhibited melanogenesis (IC₅₀ = 16.3 mmol/L), demonstrating Thiamidol’s inhibition of melanin via tyrosinase inhibition as opposed to cytotoxicity. Clinically, Thiamidol visibly reduced the appearance of age spots within 4 weeks, and after 12 weeks, some age spots were indistinguishable from the normal adjacent skin. This data demonstrates the viability of Thiamidol as a suitable anti-melanogenic ingredient for use in topical cosmetic products.

Clinical Efficacy of the Human Tyrosinase Inhibitor Thiamidol (isobutylamido thiazolyl resorcinol) in Melasma

Dennis Roggenkamp — 2025-03-17

Clinical Efficacy of the Human Tyrosinase Inhibitor Thiamidol (isobutylamido thiazolyl resorcinol) in Melasma

Dennis Roggenkamp¹, Adel Sammain¹, Manuela Fürstenau², Martina Kausch², Thierry Passeron^3,4, Ludger Kolbe²

¹International Medical Management, Beiersdorf AG, Hamburg, Germany, ²Research & Development, Beiersdorf AG, Hamburg, Germany, ³Centre Méditerranéen de Médecine Moléculaire – C3M, University Côte d’Azur, INSERM U1065, Nice, France, ⁴Department of Dermatology, University Côte d’Azur, CHU Nice, Nice, France

Thiamidol (isobutylamido thiazolyl resorcinol) was the most potent inhibitor of human tyrosinase identified out of 50,000 screened substances. In vivo, it was well tolerated and improved melasma significantly. This was the first 24-week, randomized, double-blind, vehicle-controlled, cosmetic clinical study to assess the efficacy and tolerability of Thiamidol in moderate-to-severe melasma in phototype III-V subjects with subsequent regression phase. Females allocated to the Thiamidol treatment group (n=23), applied daily Thiamidol-based Serum followed either by a Thiamidol cream with SPF 30 in the morning or by Thiamidol cream without SPF in the evening. The vehicle group (25 females) followed the same skin care routine using the corresponding vehicle formulations. Subjects returned for a follow-up visit 13-20 weeks after treatment (regression phase). Assessments included clinical photography, Melasma Area and Severity Index (MASI), skin lightness, quality of life, and tolerability. Baseline demographics and hyperpigmentation were well balanced across all treatment groups. Clinical photography and MASI improved significantly with Thiamidol versus baseline (p < 0.001) and vehicle (p < 0.001- 0.043) at all time points up to treatment end. At follow-up, MASI was still significantly lower than at baseline but similar for treatment and vehicle groups. Skin lightness and quality of life improved significantly versus baseline without significant differences between treatment and vehicle groups. This study demonstrated that Thiamidol is well tolerated and superior in improving melasma compared to baseline and vehicle over a treatment period of 24 weeks.

Clinical Evaluation of the Human Tyrosinase Inhibitor Thiamidol (isobutylamido thiazolyl resorcinol) in Prevention of UVB-induced Hyperpigmentation

Vasanop Vachiramon — 2025-03-17

Clinical Evaluation of the Human Tyrosinase Inhibitor Thiamidol (isobutylamido thiazolyl resorcinol) in Prevention of UVB-induced Hyperpigmentation

Vasanop Vachiramon, Chaninan Kositkuljorn, Kanchana Leerunyakul, Kumutnart Chanprapaph

Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Background: Thiamidol (isobutylamido thiazolyl resorcinol) has been identified as a potent human tyrosinase inhibitor. A formulation containing Thiamidol has recently shown promising efficacy for the treatment of some hyperpigmentation conditions.

Objectives: This study aimed to evaluate the efficacy and safety of a Thiamidol-based formulation in the prevention of ultraviolet (UV)-induced hyperpigmentation.

Materials and Methods: We performed a randomized, single-blinded, pilot study in healthy participants, N=30. One arm was randomly assigned to receive a Thiamidol-based formulation for three weeks. Three hyperpigmented spots were induced by UVB irradiation on both arms after 3 weeks of ITR application. Outcome evaluations included measuring mean lightness index (*L) obtained by colorimeter, hyperpigmentation scores by visual analog scale (VAS), and adverse effects.

Results: Both experimental sides showed no significant difference in terms of skin lightening after Thiamidol application. However, the Thiamidol-treated sides showed a statistically significant lower mean lightness index compared to control after an induction with UVB. In addition, the Thiamidol-treated sides had an earlier improvement and resumed normal skin color after 3 weeks post-UVB induction. A clinical evaluation by a blinded non-treating physician and subjects was more favorable on the Thiamidol-treated side than the control side (P < .05). No significant side effect was noted.

Conclusions: Thiamidol is an effective agent in the prevention of pigmentary change from UVB irradiation and may serve as a promising agent for preventing other hyperpigmentation conditions.

Effective Reduction of Acne-induced Post-inflammatory Hyperpigmentation with the Human Tyrosinase Inhibitor Thiamidol (isobutylamido thiazolyl resorcinol)

Dennis Roggenkamp — 2025-03-17

Objective: Post-inflammatory hyperpigmentation (PIH) is a major cosmetic concern especially in individuals with darker skin complexion. Unfortunately, treatment with anti-inflammatory ingredients alone does not prevent the development of hyperpigmented spots. Recently, Thiamidol (isobutylamido thiazolyl resorcinol) was described as a very potent inhibitor of human tyrosinase. The objective of this research was to investigate the potential of Thiamidol-based formulations to prevent PIH induced by acne-induced epidermal wounding.

Methods: The effect of skin care formulations containing Thiamidol on acne-related PIH was investigated in two studies; a vehicle-controlled, double-blinded, randomized clinical study, and a clinical observational study. Both studies had a duration of 3 months and included assessments of clinical photography, clinical grading and melanin index measurements.

Results: Subjects’ self-grading demonstrated that Thiamidol significantly improved the visibility of acne-induced hyperpigmentation compared to the vehicle treatment. A skin care regimen with Thiamidol significantly improved acne-related PIH over 12 weeks shown by Mexameter measurements, expert grading, self-grading and clinical photography.

Conclusion: Thiamidol represents a safe and effective ingredient for cosmetic products against post-inflammatory hyperpigmentation.

Combined Thiamidol and Low-fluence Q-switched Nd:YAG Laser for the Treatment of Facial Hyperpigmentation

Vasanop Vachiramon — 2025-03-17

Background: Thiamidol (isobutylamido thiazolyl resorcinol) is a novel human tyrosinase inhibitor recently shown to be effective in the treatment of hyperpigmentation. Low-fluence Q-switched Nd:YAG 1064-nm laser (LFQS) has proven to be effective for various hyperpigmentary conditions. However, there have been no studies to date on the efficacy and safety of combined Thiamidol and LFQS treatment.

Objectives: To compare the efficacy and safety of combined Thiamidol-based serum and LFQS with LFQS monotherapy for facial hyperpigmentation.

Materials and Methods: Patients with symmetrical facial hyperpigmentation were treated with five sessions of once weekly LFQS on the whole face. One side was randomly treated with a Thiamidol-based serum formulation and the other side received a placebo cream for 12 weeks. Patients were followed for 8 weeks after the last laser treatment. Relative lightness index (RL*I), Facial Hyperpigmentation Severity Score on the Malar Area (FHSS_m), patient satisfaction, recurrence, and adverse events were recorded.

Results: Twenty-four (N=24) patients completed the study. Both sides demonstrated significant reductions of mean RL*I and mean FHSS_m from baseline (P < .01). At the 4th week, the Thiamidol-based serum treated side showed more improvement in mean RL*I than the placebo-treated side (62.5% vs 47.3% improvement, P < .05). The mean FHSS_m on the Thiamidol-based serum treated was reduced at a significantly higher percentage than the placebo- treated side (54.4% vs 40.2% reduction, P < .05). Partial recurrence was observed on both sides. No serious side effects were noted.

Conclusion: Combined Thiamidol-based serum and LFQS therapy was more superior than LFQS monotherapy in the treatment of facial hyperpigmentation. Thiamidol-based formulations may serve as adjuvant treatment for patients with hyperpigmentation with standard therapy.

Thiamidol: A Breakthrough Innovation in Treatment of Hyperpigmentation

Seemal Desai — 2025-03-17

Skin hyperpigmentation, including melasma, solar lentigines, and post-inflammatory hyperpigmentation, results in a significant impact on patient quality of life. Unfortunately, to date, many over-the-counter (OTC) options have often been limited by efficacy, safety and tolerability concerns. Additionally, limited education on disease manifestation and root causes of hyperpigmentation often leaves patients undiagnosed and untreated. Melanogenesis is driven by a complex pathway resulting in the ultimate production and deposition of melanin in skin. The major rate-limiting step of melanogenesis centers on the conversion of L-Dopa to melanin mediated by a cellular tyrosinase, resulting in overproduction of melanin in cases of hyperpigmentation. Recently, Thiamidol (isobutylamido thiazolyl resorcinol) has been identified as the most effective inhibitor of human tyrosinase out of 50,000 compounds screened in vitro, and thus, a novel ingredient for inclusion in OTC hyperpigmentation products. Here, we describe the current pre-clinical and clinical safety and efficacy data on Thiamidol formulations, aimed at educating the dermatology community on a safe and effective OTC option for use as part of the overall management of hyperpigmentation in patients.

Evaluating the Quality of Social Media Content on Platelet-Rich Plasma for Androgenetic Alopecia and Facial Aesthetics: A Cross-Sectional Study

Aysham Chaudry — 2025-03-17

Purpose: Platelet-rich plasma (PRP) has gained popularity on social media recently for different forms of alopecia and facial aesthetics. Patients increasingly turn to social media for medical advice to help inform their treatment choice. This study assessed the quality of content, creator type, and engagement of content on PRP.

Methods: TikTok was searched using keywords related to PRP, identifying the top 180 most-liked videos, of which 140 videos met inclusion and exclusion criteria and were analyzed for duration, views, likes, creator type, and content type. Creators were categorized as dermatologists, other physicians, non-physician health care providers (NPHCPs), or laypeople. Three reviewers assessed each video using the modified DISCERN tool. Intra-class correlation (ICC) was used to determine inter-assessor reliability. An analysis of variance (ANOVA) test was used to compare mean scores across creator categories.

Results: Most videos were created by laypeople (61%) and NPHCPs (15%), with dermatologists and other physicians contributing less (11% and 12%, respectively). Most dermatologist and other physician videos were educational, while laypeople’s content was predominantly advertisements or experience-based. Overall, video quality was very poor, with median modified-DISCERN of 1. The grading scale revealed significant differences in the quality of content. Dermatologists and other physicians scored significantly higher than laypeople (p<0.004 and <0.002, respectively) and NPHCPs (p<0.04 and <0.04, respectively) on the modified-DISCERN for androgenetic alopecia. Dermatologists and other physicians scored significantly higher than laypeople (p<0.001 and <0.001, respectively) and NPHCPs (p<0.001 and <0.001, respectively) on the modified-DISCERN for facial aesthetics.

Conclusions: This analysis reveals a significant need for improved regulation and quality of medical information shared on social media platforms and increased content production of physician created videos to ensure patient safety and informed decision making.

Comparison of Dermatology Life Quality Index Scores in Adults and Adolescents With Alopecia Areata

Hannah Humphries — 2025-03-17

None.

Prediction of Long-term Scalp Hair Regrowth at 24 Months in Patients with Alopecia Areata Receiving Ritlecitinib Treatment in the ALLEGRO Clinical Trial Program

Hannah Humphries — 2025-03-17

None.

Longitudinal and Exploratory Genome-Wide Analysis in Alopecia AreaTA (LEGAATA): A Study of FinnGen Participants

Hannah Humphries — 2025-03-17

None.

The i31-SLNB Identifies Patients with Cutaneous Melanoma Who Have Less than 5% Risk of SLN Positivity while the CP-GEP does not

J. Michael Guenther — 2025-03-17

Introduction: Sentinel lymph node biopsy (SLNB) is a prognostic procedure that can help guide surveillance and treatment management plans for patients with cutaneous melanoma. However, up to 88% of SLNBs are negative, suggesting that most patients may not require SLNB. The National Comprehensive Cancer Network guidelines recommend that patients with <5% risk of SLN positivity should avoid SLNB, whereas those with a risk of 5-10% should be considered for SLNB, and those with a risk of >10% should be offered SLNB. This study compared the performance of two gene expression profile (GEP) tests designed to identify patients with low risk (<5% risk) of SLN positivity: the i31-SLNB and CP-GEP.

Methods: SLN false-negative rates were analyzed for the i31-SLNB using data from Whitman et al. (JCO PO 2021; T1-T4: n=1,258) and for the CP-GEP using publicly available data from Sondak et al. (Society for Melanoma Research 2024; T1-T3: n=1,686). Only patients who had an SLNB were included in the analysis. False negative rate (FNR) is calculated as 1-NPV.

Results: The i31-SLNB had an FNR = 3.9% in patients classified as low risk (n=233) which is below the 5% guideline cut point for avoiding an SLNB. The CP-GEP had an FNR = 7.1% in patients classified as low risk (n=624) which is above the 5% guideline cut point for avoiding an SLNB. Comparing FNRs in T1b tumors showed that the i31-SLNB had an FNR = 2.8% compared with 5.1% for the CP-GEP. Similar results were seen among T2a tumors, with the i31-SLNB having an FNR = 4.3% compared with an FNR = 7.3% for the CP-GEP.

Conclusions: The i31-SLNB accurately identifies patients with a risk of SLN positivity below the NCCN guideline of 5% risk threshold for avoiding SLNB, with a false-negative rate nearly 50% lower than that of CP-GEP. Conversely, patients identified as low risk by CP-GEP had SLN positivity rates over 5%, suggesting it is not sufficient for informing clinical decisions regarding SLNB.

Enabling Access to Prognostic Gene Expression Profile (GEP) Testing for Invasive Melanoma by Leveraging RNA-based Testing in the Diagnostic Workflow

Brooke Russell — 2025-03-17

Background: 31-GEP prognostic testing is an important tool for patients diagnosed with invasive melanoma and stratifies patients into groups at low, intermediate, or high risk of recurrence, metastasis, or death. The pathway to a melanoma diagnosis is not always straightforward and often dermatopathologists utilize molecular testing to assist in the accurate classification of ambiguous lesions, which utilize varied tissue amounts. Separately, the 23-GEP test is an objective molecular ancillary diagnostic test which uses RNA extracted from 9 unstained slides. Both diagnostic (23-GEP) and prognostic (31-GEP) tests are offered from the same laboratory and can utilize the same RNA. Here, 23-GEP clinical order trends are described March through July 2023.

Methods: 23-GEP orders from March through July 2023 were analyzed.

Results: 23-GEP tissue was primarily obtained from shave biopsies (88.6%, where biopsy type was specified). 57.5% of samples were female and median patient age was 49.5 years old. The test result distribution was 61.8% benign, 20.3% malignant, 13.7% intermediate, and 4.2% technical fail. Median turnaround time (TAT) (calculated as receipt of tissue until report date and inclusive of weekends and holidays) of 23-GEP was 4 days (interquartile range = 2, 5). If a 23-GEP-tested clinical order subsequently receives an invasive melanoma diagnosis, 31-GEP can be utilized efficiently without additional tissue and RNA extraction time.

Conclusions: Overall, when the 23-GEP ancillary test is utilized to achieve a confident diagnosis in an otherwise ambiguous neoplasm, rapid access to 31-GEP prognostication without the need for additional tissue can be achieved.

The Calculated Objective Response Rate (ORR) of 97% from Post-Hoc Analysis of a Phase 2 Multicenter Study to Evaluate the Efficacy of VP-315, an Investigational therapy for Basal Cell Carcinoma (BCC)

Jonathan Kantor — 2025-03-17

Introduction

Objective response rate (ORR), defined as the percentage of patients achieving a complete or partial response to treatment, is a critical endpoint in clinical trials assessing the efficacy of new therapies in solid tumors, including BCC.

We performed a post-hoc analysis exploring ORR as a potential primary endpoint for future studies evaluating the efficacy of VP-315, an intratumorally injected, chemotherapeutic oncolytic peptide.

Objective

To evaluate the effect of various VP-315 8 mg dosing regimens on antitumor response in subjects with BCC.

Methods

Eighty-two 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.

Post-hoc evaluation by ORR was based on response defined a priori as absence of disease progression and ≥30% reduction in lesion size from baseline, or complete resolution of ulceration in all target lesions. Complete response was based upon objective response with no residual BCC on post-treatment excisional biopsy. Partial response was objective response with presence of residual BCC.

Results

Eighty-two subjects (n=91 tumors) treated with VP-315 had a calculated ORR of 97%. Response rates were: 52% complete response and 45% partial response. No TRSAEs were reported. TRAEs were mostly mild to moderate.

Conclusion

These results support further investigation of ORR as a reliable endpoint for VP-315 in future BCC studies. Additional 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.

Factors Associated with Advanced Presentations of Melanoma in the United States from 2004-2015: A National Cancer Database Analysis Cohort Study

Kennedy Sabharwal — 2025-03-17

Purpose: Significant advances have been made in the diagnosis and treatment of melanoma, but mortality remains high. The primary aim of this study was to identify risk factors associated with advanced presentations of melanoma in the US.

Methods and Materials: Stage III and IV melanoma were identified in the National Cancer Database (NCDB) with appropriate staging and pathologic confirmation from 2004-2015. Patient-specific variables were analyzed using chi square and binary logistic regression multivariate analyses to elucidate factors associated with advanced stage melanoma at diagnosis.

Results: There were 477,914 patients meeting inclusion criteria, 63,291 (13.2%) presenting with advanced stage. Factors associated with advanced presentation included lower income, non-Hispanic white race, Medicaid/uninsured insurance, greater distance to treatment centers, male gender, younger age, more medical comorbidities, and southeast U.S. location (p < 0.05, each). All factors were statistically significant on multivariate analysis.

Conclusion: Age, gender, race/ethnicity, geographic location, socioeconomic factors, and distance to treatment center are associated with advanced melanoma diagnosis. Melanoma screening and education should target these groups, and more research is necessary to elucidate causes of the disparities that may preventing the early diagnosis of melanoma for these patients.

Olive Oil in Dermatology: Bridging Ancient Traditions with Modern Medicine

Zaryab Alam — 2025-03-17

Olives, a staple of Mediterranean culture, hold significant historical, spiritual, and cultural importance, particularly in Islamic traditions. This review explores the use of olives and their derivatives in complementary and alternative medicine, focusing on dermatological applications. A systematic literature review using EMBASE and PubMed databases, adhering to PRISMA guidelines, identified 44 articles for inclusion. Olive oil demonstrated effectiveness in reducing erythema, scaling, and pain associated with radiation and contact dermatitis, and in managing symptoms of atopic dermatitis and psoriasis through modulation of inflammatory pathways. It also promoted wound healing, benefiting patients with pressure ulcers, chronic wounds, and burns. Additionally, the Mediterranean diet, rich in olives, was linked to reduced inflammation in conditions like cystic acne and hidradenitis suppurativa. These dermatological benefits are attributed to the antioxidant and anti-inflammatory properties of olive's phenolic compounds. This review highlights olives’ potential in dermatology as a natural, affordable treatment option, encouraging further research into their therapeutic applications.

Ocular Disease as a Comorbidity of Atopic Dermatitis

Kimberlee Tottori — 2025-03-17

A variety of ocular disorders are commonly encountered in individuals affected by atopic dermatitis (AD). In addition to commonly observed ocular surface disease (OSD), other comorbid eye disorders seen inherently with AD include infections, keratoconjunctivitis, cataracts, and keratoconus. Some ocular diseases are recognized as potential adverse effects of therapies used to treat AD, especially topical and systemic corticosteroids, and biologic agents that inhibit interleukins (IL) 4 and/or 13. The latter includes dupilumab (IL-4/IL-13), tralokinumab (IL-13), and lebrikizumab (IL-13), all of which may be associated with OSD. This article serves to provide a thorough review of ocular diseases that are comorbidities of AD and/or occur in association with therapies used to treat AD.

Expanding Therapeutic Applications of Tofacitinib in Immune-Mediated Skin Disorders: A Comprehensive Review

Nina Schur — 2025-03-17

Tofacitinib, a Janus kinase (JAK) inhibitor targeting JAK1 and JAK3, has gained attention for its immunomodulatory effects, particularly in autoimmune and inflammatory conditions. While initially approved for rheumatoid arthritis, its off-label uses in dermatology are expanding, with promising results in conditions such as vitiligo, alopecia areata, atopic dermatitis, psoriasis, and plaque psoriasis. By inhibiting the JAK-STAT signaling pathway, tofacitinib reduces cytokine-mediated inflammation and immune cell activation, offering a novel therapeutic option for dermatological disorders where traditional treatments have failed. This review explores the pharmacology of tofacitinib, its current off-label dermatological uses, and future research opportunities. It also addresses challenges related to long-term safety, accessibility, and treatment resistance. Ongoing clinical trials and potential new indications, as well as combination therapies, are discussed, highlighting tofacitinib's evolving role in dermatology.

Challenges in Public Health: The Diagnosis and Treatment of Crusted Scabies

Alyssa Forsyth — 2025-03-17

Introduction: Common scabies is a parasitic dermatologic condition that often presents as an extremely pruritic rash. A rare and highly contagious variant of common scabies is crusted scabies, formerly known as Norwegian scabies. While infection with common scabies typically involves 10 to 20 mites, individuals with crusted scabies are burdened with thousands to millions of mites. Crusted scabies is characterized clinically by hyperkeratotic papules and plaques, most commonly on the palms and soles. Due to the variety of presentations seen in scabies, it can be difficult to diagnose.

Case Presentations: We present four cases of crusted scabies. An 89-year-old male with a history of dementia presented with a two-month history of a generalized pruritic rash. A 22-year-old male with a history of trisomy 21 presented with a 10-month history of mildly pruritic rash on the hands. A 54-year-old female with a history of trisomy 21 and cutaneous T-cell lymphoma presented with a three-week history of a generalized pruritic rash. Lastly, a five-year-old male with acute lymphoblastic leukemia with a minimally pruritic rash on his hands and elbows that had spread to the genitals. The patients were diagnosed with skin scrapings or biopsy showing scabies mites. These patients were all treated with extended courses of oral and topical anti-parasitic medications.

Discussion/Conclusion: Crusted scabies poses a significant challenge to public health as a severe variant of scabies associated with high morbidity and mortality. It is most commonly seen in persons who are immunosuppressed, have an underlying neurologic disorder, or are immobile. Patients may present with skin eruption and pruritus. Patients can also present with severe illness such as erythroderma, which poses a risk for hypothermia, acute respiratory distress syndrome, sepsis, and high-output heart failure. Scabies-related mortality in crusted scabies is high. Management of crusted scabies is different than for other types of scabies because the patient is infested with large numbers of mites. Patients may also have an altered immune response. Treatment of crusted scabies requires a combination of oral and topical treatments. Lastly, the large number of mites in crusted scabies requires more rigorous evaluation and treatment of contacts than other types of scabies. This is necessary to prevent or limit scabies outbreaks and re-infection. As many patients with crusted scabies live in congregate facilities, this requires prompt evaluation of contacts with treatment of cases and public health treatment of asymptomatic residents, staff, and visitors.

Early Acne Improvements With Fixed-Combination Topical Therapy: Analysis of the First 4 Weeks of Treatment

Steven R. Feldman — 2025-03-17

Background: Acne treatment can take weeks to result in noticeable improvements, which may diminish patients’ perception of treatment effectiveness and negatively affect treatment adherence. Acne treatments that deliver early visible improvements may encourage treatment adherence and bolster overall treatment effectiveness. Combination topical treatments that target multiple acne pathophysiological pathways are more efficacious than monotherapies and simplifying the treatment regimen by delivering multiple active ingredients as fixed combinations may improve adherence.

Objective: To evaluate early acne improvements in clinical trials of fixed-combination acne topicals.

Methods: Week 4 efficacy data for fixed-combination topical treatments were gathered from US Food and Drug Administration medical reviews, prescribing information, and/or publications of pivotal phase 2 and phase 3 clinical trials of 7 acne topicals, comprising fixed combinations of adapalene (ADAP), benzoyl peroxide (BPO), clindamycin phosphate (CLIN), and tretinoin. For the triple-combination formulation (CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel), data from a nonpivotal phase 2 study with dyad combination treatment arms were also included. Outcomes included reductions from baseline in inflammatory lesions (ILs) and noninflammatory lesions (NILs) and treatment success (≥2-grade reduction in global acne severity score and clear/almost clear skin).

Results: At week 4, IL reductions from baseline ranged from 32-54% while NIL reductions ranged from 25-45%. Rates of treatment success ranged from 3-12%. Overall, efficacy was greatest with triple-combination CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel (IL: 54-55%; NIL: 43-45%; treatment success: 8-12%), followed by combinations of ADAP/BPO (IL: ~42-48%; NIL: ~38%; treatment success: 4-~7%). None of the branded topical products were evaluated in a head-to-head study.

Conclusions: In pivotal clinical trials of topical fixed-combination formulations for acne, triple-combination CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel yielded greater lesion reductions and rates of treatment success after 4 weeks of treatment than dyad formulations. Even greater differences may be expected with real-world world use, as early improvements may foster better long-term outcomes by increasing patients’ confidence in and adherence to the treatment.

Funding: Ortho Dermatologics

Fixed‑Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Versus Adapalene 0.3%/Benzoyl Peroxide 2.5% Gels for Moderate‑to‑Severe Acne: Comparative Patient Journey

Lawrence Green — 2025-03-17

Background: The American Academy of Dermatology recommends combination treatment for most patients with acne, but adding ingredients to a treatment regimen may increase the risk of adverse effects. Clindamycin phosphate 1.2%/adapalene (ADAP) 0.15%/benzoyl peroxide (BPO) 3.1% (CAB) gel is the only triple-combination fixed-dose topical formulation for acne. In clinical studies, CAB gel demonstrated superior efficacy to vehicle and component dyad gels, with good safety/tolerability.

Objectives: Document the treatment journey of clinical trial participants treated with either CAB gel or branded ADAP 0.3%/BPO 2.5% gel.

Methods: In a phase 2, double-blind, 12-week study (NCT04892706), participants aged ≥12 years with moderate to severe acne were randomized to once-daily CAB, branded ADAP 0.3%/BPO 2.5% (ADAP/BPO), or vehicle gel. Assessments included treatment success (≥2-grade reduction in Evaluator’s Global Severity Score [EGSS] and clear/almost clear skin), change from baseline in inflammatory (IL) and noninflammatory lesions (NIL), treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. Descriptive data are summarized for 4 pairs of participants treated with CAB or ADAP/BPO; each pair was matched for baseline characteristics, acne severity, and lesion counts.

Results: Participant ages ranged from 13-21 years. At week 12, 3 of 4 CAB-treated and 1 of 4 ADAP/BPO-treated participants achieved treatment success. IL reductions from baseline with CAB and ADAP/BPO ranged from 63.1%-100% and 40.6%-81.8% respectively. NIL reductions ranged from 55.8%-98.0% with CAB and 32.4%-94.3% with ADAP/BPO. One participant reported a treatment-related TEAE (CAB-treated; moderate stinging; resolved) and no serious treatment-related TEAEs were reported. Transient increases in cutaneous safety/tolerability resolved to or near baseline by week 12.

Conclusions: In 4 matched participant pairs, treatment success and lesion reductions were greater overall with CAB gel than with ADAP/BPO gel, with similar safety/tolerability findings. In conjunction with results from the overall participant populations of CAB clinical trials, these data illustrate the potential of CAB gel as the only triple fixed-combination treatment option in the acne armamentarium.

Funding: Ortho Dermatologics

Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Acne: Association of Efficacy With Cutaneous Safety/Tolerability Events

Steven R. Feldman — 2025-03-17

Background: Topical treatment of acne—particularly with retinoids—often incurs a transient period of dermal irritation characterized by erythema, scaling, and other dermal changes that may reflect the same mechanisms of action by which acne pathophysiology is addressed. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel demonstrated efficacy in the treatment of acne, with a safety/tolerability profile typical of topical acne treatment. The objective of this post-hoc analysis is to determine whether CAB efficacy was related to occurrence of cutaneous safety/tolerability events.

Methods: Data were pooled from 4 double-blind, 12-week studies of participants with moderate-to-severe acne. Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory (IL) and noninflammatory lesions (NIL). Cutaneous safety/tolerability assessments of erythema and scaling (investigator-assessed) and itching, burning, and stinging (participant-assessed) were graded on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). To determine if CAB efficacy was associated with cutaneous events, efficacy endpoints at week 12 were compared for CAB-treated participants who experienced no increase versus ≥1-grade (any) increase in any safety/tolerability score at weeks 2, 4, or 8.

Results: At week 12, CAB-treated participants experiencing any safety/tolerability event (n=411) had significantly greater rates of treatment success and IL reductions, and numerically greater NIL reductions, than those without events (n=188; treatment success: 55.0% vs 43.0%; P<0.01; IL reductions: 79.1% vs 72.3%; P<0.001; NIL reductions: 73.1% vs 68.1%). At weeks 2, 4, and 8, IL/NIL reductions were significantly greater among participants experiencing any cutaneous event than those without events (P<0.05, all). Overall, improved efficacy appeared to be driven by events of scaling, itching, and burning.

Conclusions: Across four clinical studies, CAB-treated participants who experienced safety/tolerability events at weeks 2, 4, or 8 also experienced greater lesion reductions across 12 weeks of treatment and greater rates of treatment success at week 12. These findings are consistent with the theory that early instances of cutaneous irritation during topical acne treatment may reflect therapeutic mechanisms of action. Setting patient expectations regarding the potential for transient irritation during treatment may contribute to greater adherence and efficacy with CAB gel.

Funding: Ortho Dermatologics

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

Glynis Ablon — 2025-03-17

Background: Triple-combination therapies for acne including an antibiotic, topical retinoid, and benzoyl peroxide (BPO) are more effective than dual combinations or topical monotherapy. In clinical studies of participants with moderate to severe acne, clindamycin phosphate (CLIN) 1.2%/adapalene (ADAP) 0.15%/BPO 3.1% (CAB) gel demonstrated superior efficacy to vehicle and component dyads, with good safety and tolerability. Because acne pathogenesis and presentation can vary by skin type and ethnicity, it is important to assess treatment outcomes for specific populations. This post hoc analysis assessed efficacy and safety of CAB gel in Caucasian participants.

Methods: Data were pooled from two phase 2 and two phase 3 double-blind, 12-week studies of participants with moderate to severe acne (N=1787). The pooled population included 1283 self-identified Caucasian participants, randomized to 6 treatment arms: once-daily CAB gel (n=446), ADAP 0.15%/BPO 3.1% gel (n=109), CLIN 1.2%/BPO 3.1% gel (n=101), CLIN 1.2%/ADAP 0.15% gel (n=109), branded ADAP 0.3%/BPO 2.5% gel (n=165), and vehicle (n=353). Endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory/noninflammatory lesions. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were also assessed.

Results: At week 12, a significantly greater percentage of Caucasian participants achieved treatment success with CAB gel (51.5%) than dyads (range, 31.7%-34.3%), randed ADAP 0.3%/BPO 2.5% gel (33.5%), or vehicle (17.9%; P<0.01, all). CAB yielded significantly greater reductions from baseline in inflammatory and noninflammatory lesions (76.8% and 73.0%, respectively) than dyads (62.7%-70.2% and 60.9%-63.4%, P<0.01, all), randed ADAP 0.3%/BPO 2.5% gel (72.6% and 65.7%, P<0.05, both) and vehicle (52.3% and 44.8%, P<0.001, both). Most TEAEs were of mild to moderate severity; the most common treatment-related TEAEs were application site pain, dryness, dermatitis, and erythema. Transient increases in cutaneous safety/tolerability scores beginning at week 2 resolved back to or near baseline by week 12; all scores were <1 (mild) at all post-baseline assessments.

Conclusions: In Caucasian participants with moderate to severe acne across 4 clinical studies, triple-combination CAB gel demonstrated significantly greater efficacy without worsening tolerability vs dyad gels, randed ADAP 0.3%/BPO 2.5% gel, or vehicle.

Funding: Ortho Dermatologics

Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Acne: Pooled Analysis by Age and Sex

Julie C. Harper — 2025-03-17

Background: Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel demonstrated efficacy in the treatment of acne, with a good safety/tolerability profile, in participants with moderate to severe acne. Acne clinical presentation and response to treatment may differ between males and females as well as between pediatric-postadolescent (<24 years) and adult (≥25 years) patients. The objective of this post hoc analysis was to evaluate the impact of age and sex on the efficacy and safety of CAB gel.

Methods: In one phase 2 and two phase 3 double-blind, 12-week studies, participants with moderate-to-severe acne were randomized to once-daily CAB or vehicle (Veh). Data were analyzed post hoc for participants categorized by age and sex: females 9-24 or ≥25 years (ns=274 and 121) and males 9-24 or ≥25 years (ns=241 and 21). Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory and noninflammatory lesions (IL/NIL). Treatment-emergent adverse events (TEAEs) were also assessed.

Results: At week 12, a greater percentage of participants in all sex/age subgroups achieved treatment success with CAB (42.3-54.1%) than Veh (15.0-22.5%). Similarly, lesion reductions were larger with CAB than Veh (IL: CAB, 75.9-77.8%; Veh, 50.8-65.2%; NIL: CAB, 69.7-73.7%; Veh, 44.5-55.2%). For all efficacy endpoints, CAB was statistically superior to Veh among males and females 9-24 years and females ≥25 years (P≤0.05, all). For males ≥25 years, only NIL reductions were significantly greater with CAB (P≤0.05), likely due to the small population. For all CAB-treated groups, most TEAEs were of mild-moderate severity. Rates of TEAEs deemed related to CAB treatment were similar for males and females 9-24 years (19.7% and 18.6%, respectively) and somewhat higher for females ≥25 years (24.4%). Considerably lower treatment-related TEAE rates in males ≥25 years (8.3%) may reflect the low number of participants in this group (n=12 treated with CAB).

Conclusions: In 3 clinical trials, participants treated with CAB gel—the only fixed-dose, triple-combination topical for acne—experienced ≥70% lesion reductions, and approximately half achieved clear or almost clear skin. CAB gel demonstrated good efficacy and tolerability regardless of participants’ sex or age.

Funding: Ortho Dermatologics

Bimekizumab Impact on Flare in Hidradenitis Suppurativa Over 2 Years: Data from BE HEARD EXT

Haley B. Naik — 2025-03-17

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterised by recurrent nodules, abscesses and draining tunnels, with patients often experiencing periodic worsening of symptoms, known as flares.¹ Achieving disease control is important to reduce flare frequency.¹ Bimekizumab (BKZ) is a humanised monoclonal IgG1 antibody which selectively inhibits interleukin (IL)-17A and F.² We report the proportion of patients who experienced a flare at a given visit and the cumulative proportion of patients who remained flare-free up to Weeks (Wks)48 and 96, from the BE HEARD I&II trials and their OLE, BE HEARD EXT, in patients with moderate-to-severe HS.^3,4

Procedure: Data pooled from the BE HEARD I&II studies and BE HEARD EXT. Wk48 completers could enroll in BE HEARD EXT and receive open-label BKZ 320 mg Q2W/Q4W based on ≥90% HS Clinical Response (averaged from BE HEARD I&II Wks36, 40 and 44).

Patients randomised to receive BKZ from baseline in BE HEARD I&II and who entered BE HEARD EXT were included (BKZ Total). Flare defined as ≥25% increase in abscess and inflammatory nodule (AN) count with an absolute increase in AN count of ≥2 relative to baseline. Proportion of patients who experienced a flare at the given visit (single point) and cumulative proportion (any visit up to and including the given timepoint) who remained flare-free up to Wks48 and 96 are reported as OC.

Results: 556 patients randomised to BKZ in BE HEARD I&II completed Wk48 and entered BE HEARD EXT; 446 of these completed a lesion count assessment at Wk96. At Wk48, (12/556 [2.2%]) patients in BKZ Total experienced a flare. This low rate was maintained at Wk96 (5/446 [1.1%]). Most (466/556 [83.8%]) patients in BKZ Total remained flare-free to Wk48; this was maintained through Wk96 (372/446 [83.4%]).

Conclusion: The majority of patients with moderate-to-severe HS treated with bimekizumab did not experience a flare at any given study visit and remained flare-free through 2 years.

Funding: UCB. Medical writing provided by Costello Medical. Previously submitted to EHSF 2025.

Topical Antifungals for Onychomycosis: In Vitro Antifungal Activity, Ex Vivo Nail Penetration, and Clinical Efficacy

Ali Elabbasi — 2025-03-17

Background: Topical treatment of toenail onychomycosis may be preferred for patients for whom systemic adverse events, drug-drug interactions, and contraindications associated with oral antifungals are of concern. Three topical antifungals have been approved by the US Food and Drug Administration (FDA) for the treatment of toenail onychomycosis: ciclopirox 8% lacquer, efinaconazole 10% solution, and tavaborole 5% solution. In the absence of head-to-head clinical trials, the objective of this review is to compare in vitro antifungal activity, ex vivo human nail penetration, and clinical efficacy of these topical onychomycosis treatments.

Methods: In vitro antifungal activity, defined as the minimum concentration of drug needed to inhibit 90% of fungal growth (MIC₉₀), was assessed for each antifungal against Trichophyton rubrum and T. mentagrophytes, the most common causative fungi in onychomycosis (lower MIC=greater antifungal activity). To assess nail penetration, each antifungal was applied to a human cadaverous toenail; disks punched from the coated nails were placed onto agar plates seeded with clinical isolates of each fungal species. After incubation, antifungal activity was measured as the radius of the area of no fungal growth (zone of inhibition; ZI). Clinical efficacy data were gathered from prescribing information and/or publications of pivotal phase 3 clinical trials, in which each drug was applied daily for 48 weeks (plus debridement with ciclopirox). Outcomes were mycologic cure (negative fungal culture and negative KOH staining), complete/almost complete cure (mycologic cure and ≤5-10% target nail involvement), and complete cure (mycologic cure and 0% target nail involvement).

Results: Efinaconazole demonstrated the greatest in vitro antifungal activity against both Trichophyton species. MIC₉₀ values for efinaconazole ranged from 0.008-0.125 mg/mL, compared with 0.25-0.5 mg/mL for ciclopirox and 8 mg/mL for tavaborole. In the ex vivo nail penetration assay, ZIs for efinaconazole (T. rubrum: 82.1 mm; T. mentagrophytes: 63.8 mm) were significantly greater than for ciclopirox and tavaborole (7.4-63.5 mm and 3.6-39.1 mm, respectively; P<0.001, all). Accordingly, efinaconazole demonstrated greater clinical efficacy, with higher rates of mycological cure (53.4-55.2% vs 29.0-36.0% for ciclopirox and tavaborole), complete/almost complete cure (23.4-26.4% vs 6.5-17.9%), and complete cure (15.2-17.8% vs 5.5-9.1%).

Conclusions: Among FDA-approved topical therapies approved for the treatment of toenail onychomycosis, efinaconazole 10% solution demonstrated the greatest in vitro antifungal activity, human nail penetration, and clinical efficacy.

Funding: Ortho Dermatologics.

Efficacy and Safety of Efinaconazole 10% Topical Solution for Onychomycosis Treatment in Older Adults

Shari Lipner — 2025-03-17

Background: Toenail onychomycosis treatment is challenging, especially in older adults, due to slower nail growth, increased nail thickness, and greater likelihood of concomitant medication use and comorbidities (eg, diabetes, peripheral vascular disease, reduced renal function). Unfortunately, published efficacy and safety data in older adults are limited. Efinaconazole 10% solution has demonstrated efficacy and favorable tolerability in two phase 3 studies and in post hoc analyses of participant sex, ethnicity, age, baseline disease severity, and concurrent diabetes. Here, pooled post hoc analyses were conducted to evaluate efficacy and safety of efinaconazole in participants aged ≥65 years with mild to moderate onychomycosis.

Methods: Data were pooled from 2 multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (NCT01008033, NCT01007708) of participants aged 18-70 years with mild to moderate distal lateral subungual onychomycosis affecting ≥1 great toenail. Participants (n=1,655) were randomized (3:1) to topical efinaconazole 10% or vehicle applied once daily for 48 weeks, with a follow-up visit at week 52. Efficacy endpoints included rates of complete cure (0% clinical involvement of target toenail + negative potassium hydroxide [KOH] examination + negative fungal culture), mycologic cure (negative KOH + negative fungal culture), complete/almost complete cure (≤5% clinical involvement + mycologic cure), unaffected new toenail growth (change from baseline in unaffected toenail measurement), and clinical efficacy (<10% clinical involvement) at week 52. Adverse events (AEs) were also assessed. Only participants aged ≥65 years were included in these analyses (n=162 efinaconazole; n=56 vehicle).

Results: At week 52, significantly more older adults treated with efinaconazole vs vehicle achieved a complete cure (13.6% vs 3.6%) or a complete/almost complete cure (19.1% vs 5.4%; P<0.05, both). Over half of participants treated with efinaconazole (59.2%) achieved mycologic cure vs 12.5% with vehicle (P<0.001). Least squares mean unaffected new nail growth was significantly greater with efinaconazole vs vehicle (3.9 mm vs 0 mm; P<0.001), and a quarter of participants achieved clinical efficacy with efinaconazole (25.3%) vs 14.3% with vehicle (P<0.05). Most treatment-emergent AEs with efinaconazole were mild to moderate in severity, and discontinuation rates were low (<4.5%), in line with the overall phase 3 populations.

Conclusions: Topical efinaconazole 10% solution showed good efficacy and safety in participants aged ≥65 years with mild to moderate onychomycosis, despite possible age-related changes in nail growth. These results were in line with the overall phase 3 populations, demonstrating that efinaconazole is an efficacious treatment for older adults for whom there is a dearth of clinical data.

Funding: Ortho Dermatologics

Inclusion of the Patient Voice in Developing Holistic Treatment Goals for Rare Skin Diseases

Emmylou Casanova — 2025-03-17

Treatment goals for generalized pustular psoriasis (GPP) are poorly defined, based mostly on data from plaque psoriasis, and are not reflective of the patient experience. Shared decision-making between patients and physicians around treatment goals can lead to improved outcomes and patient satisfaction. Furthermore, health regulatory bodies have issued guidance on the integration of patient experience data, along with other insights from patients and caregivers into the development of new treatments. Patient perspectives have been incorporated into consensus-shaping exercises to better understand treatment goals for plaque psoriasis, though a similar approach has been lacking in GPP. Here, we report insights from the first consensus-shaping exercise in GPP to incorporate the patient perspective.

An expert panel was assembled comprising patient representatives and dermatologists with recent or current experience in treating GPP. Through the use of a targeted questionnaire (based on a systematic literature review), the objective was to achieve consensus on key principles of GPP treatment, including short-term and long-term goals. Patients and physicians rated their level of agreement on 26 different statements and gave additional comments in a free-text field. Consensus per statement was defined as ≥80% agreement across the panel.

The panel comprised 30 dermatologists and 3 patient representatives. Each of the 3 patients (Asia, n=2; USA, n=1) had >10 years’ lived experience of GPP; one patient was a member of a GPP patient advocacy group. Consensus between physicians and patients was reached on all statements relating to effective disease management, including the need for tailored treatment plans. Overall, physicians considered the treatment of certain symptoms (e.g. skin pustules) as the most important clinical goal and metric for treatment success. However, patients considered alleviation of other symptoms (alongside skin and systemic symptoms) to be equally important due to the psychological and emotional impact of this in their daily lives.

Developing treatment goals for rare skin diseases such as GPP is challenging due to limited published evidence on symptom burden and a relative lack of approved treatment options. The inclusion of patient representatives in this consensus-shaping exercise for GPP provided personal insights regarding the wider impact of the disease on patients’ lived experience. Patients should be empowered as active, shared decision-makers to ensure that treatment goals for chronic diseases are holistic, reflecting not only clinical outcomes, but also symptoms that have the greatest impact on quality of life.

Funding

This study was supported and funded by Boehringer Ingelheim.

Emotional Anatomy: Botulinum Toxin and the Regulation of Mood

Robert Vanaria — 2025-03-17

Purpose: Emotions are expressed via coordinated contraction of the small muscles of the face to convey psychological expression. Manipulation of this coordinated movement can affect the emotions that patients experience and results in an influence of limbic system activity. Botulinum toxin is the most popular cosmetic procedure for correction of contraction-associated fine lines and wrinkles, and acts via temporary muscle relaxation. This review explores the effects that botulinum toxin has on specific muscle groups and thereby on emotional expression and feeling.

Methods: A literature review regarding understanding of facial anatomy and expressions as well as botulinum toxin’s effect on emotions and communication was conducted via PubMed using search terms such as “botulinum toxin” AND “emotion”. Results were screened for relevance and to include English-only articles. Further articles were included through citation tracking. Authors’ clinical experience was also included.

Results: A total of 50 articles were included based on relevance and search terms. Two additional book chapters were added from author knowledge. Biological feedback from the facial feedback, facial mimicry, and emotional contagion are the basis of botulinum toxin-induced emotional influence. The paralysis of muscles associated with frowning (glabellar complex) and smiling (zygomaticus and orbicularis oculi) as a treatment for wrinkles and fine lines can result in patients experiencing more or less positive or negative emotions, depending on which muscles are targeted. Patients treated in the glabellar region only with botulinum toxin reported significant increases in their mood, which was attributed to their acquired inability to produce a frown. This included clinically depressed patients who experienced a significant improvement in depression scores or resolution of depression altogether. Treatment of the “crow’s feet” region canceled the glabella effect when treated alone, resulting in a more negative mood.

Conclusions: Facial expressions can influence mood states and perception of emotions. Although known traditionally as a cosmetic treatment, botulinum toxin can also be used to influence patient mood via facial muscle paralysis, and importantly, offers an alternative treatment modality for depression.

Ratio of Nonmelanoma Skin Cancer Histologic Subtypes in a South Florida Dermatology Practice: High Incidence of Squamous Cell Carcinoma Subtypes

Angelica Marrero-Perez — 2025-03-19

Background: Ultraviolet Radiation (UVR), both UVA and UVB, are established causes of nonmelanoma skin cancers (NMSC); primarily basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) subtypes. Because of its demographics and geographic location, the population of Florida is at risk for some of the highest rates of NMSC in the world. While current dermatologic epidemiology states that over 70% of NMSC are BCC, a previous 2012 study in South Florida showed a much higher incidence of SCC subtypes.

Methods: The electronic histopathology database associated with a clinical dermatology practice in South Florida was searched for all histologically-confirmed NMSC results across all ages for the full year of 2024.

Results: A total of 856 lesions with biopsy-proven NMSCs were assessed and categorized into BCC and SCC subgroups. BCC subgroups included superficial, nodular, morpheaform, and other subtypes. SCC subgroups included in situ SCC (isSCC) and all invasive SCC subtypes, including SCC and keratoacanthoma type. Among these lesions, 247 (28.9%) were BCC subtypes and 609 (71.1%) were SCC subtypes. Further categorized, 54 were superficial BCC (6.24%), 193 were BCC (22.31%), 268 were isSCC (30.98%), and 341 were SCC (39.42%).

Discussion: The 2024 incidence rates reveal very high ratios of SCC versus BCC. Our findings are in line with the findings from the previous study from South Florida, which may challenge the historical ratio of BCC to SCC. In this study, SCC subtypes including isSCC represented over 70% of all biopsy-confirmed NMSC. We hypothesize this trend may be attributed to different factors. First, the historical use of UVB-specific over more modern broad-spectrum sunscreens allowed for much greater UVA exposure without UVB burns may account for the higher rates of SCC. Indeed, the ratio of this patient cohort more closely mimics long term PUVA or organ transplant populations. Since many SCC subtypes may arise from Actinic Keratoses (AK) current dermatologists may be misdiagnosing early SCC including isSCC as AK and directly destroying the lesions with liquid nitrogen instead of taking a biopsy to determine if they are SCC. Additionally, this study highlights the importance of treating AK to prevent future SCC.

Conclusion: Our patient population showed a significantly higher incidence of SCC than BCC within NMSC, which contradicts current teachings. Further study is warranted.