Lebrikizumab Dosed Every 8 Weeks as Maintenance Provides Long-Lasting Response in Patients with Moderate-to-Severe Atopic Dermatitis

Abstract

Introduction Lebrikizumab dosed every 4 weeks (LEBQ4W) in ADjoin demonstrated sustained response up to 3 years in patients with atopic dermatitis (AD) who were Week-16 responders. In ADvocate1/ADvocate2 during the maintenance period (Weeks 16-52), a high proportion of patients exhibited durable efficacy in the lebrikizumab withdrawal (placebo) arm, suggesting the possibility of less frequent dosing. We report results from a 32-week extension to ADjoin assessing efficacy and safety of LEBQ8W.

Methods ADjoin is a 100-week long-term extension study assessing lebrikizumab 250 mg every 2 weeks (LEBQ2W) and every 4 weeks (LEBQ4W) in patients who completed qualifying parent studies. Qualifying patients from ADvocate1, ADvocate2, ADore, and ADopt-VA who completed ADjoin Week 100 were re-randomized to open-label LEBQ8W or LEBQ4W for a 32-week extension. Primary outcomes were percentages of patients achieving Investigator’s Global Assessment score of 0 or 1 (IGA 0/1) and ≥75% improvement in Eczema Area and Severity Index (EASI 75) at Week 32. Key secondary outcomes included percentage of patients achieving EASI 90 and change from baseline in the Patient-Oriented Eczema Measure (POEM). Safety data were collected throughout the extension. A combined non-responder imputation and multiple imputation method were used to address intercurrent events and missing data. The study was not powered to detect if LEBQ4W dosing is comparable to LEBQ8W dosing.

Results 103 patients (LEBQ8W, N=51; LEBQ4W, N=52) enrolled in the 32-week extension (mean 60 days without lebrikizumab from ADjoin Week 100 to start of extension). Mean values for parent study baseline characteristics in LEBQ8W and LEBQ4W, respectively, were: AD disease duration, 17.1 and 17.7 years; EASI, 31.0 and 26.6; body surface area, 48.3% and 39.3%; and POEM, 20.9 and 19.8. Upon entering the extension, 64.7% and 73.1% of LEBQ8W and LEBQ4W patients, respectively, had achieved EASI 90, and mean (SD) POEM scores were 8.7 (7.6) and 6.0 (5.4), respectively. At Week 32 of the extension, percentages of patients (95% confidence interval) who achieved IGA 0/1 were 62.0% (48.3, 75.8) and 73.0% (60.9, 85.1) in LEBQ8W and LEBQ4W, respectively; 79.1% (67.6, 90.5) and 86.2% (76.8, 95.7) of patients achieved EASI 75 and 68.7% (55.8, 81.6) and 78.2% (66.8, 89.5) achieved EASI 90; POEM mean (SD) absolute scores (as observed) were 9.2 (7.3) in LEBQ8W and 5.4 (5.2) in LEBQ4W. All adverse events (AEs) were mild or moderate in severity. No serious AEs or AEs leading to discontinuation were reported; there was no evidence of increased risk of anti-drug antibodies with less frequent dosing.

Conclusion Lebrikizumab dosed every 8 or 4 weeks provided long-lasting response in patients with moderate-to-severe AD, supporting its durable and potential disease-modifying effect in AD.