Lebrikizumab Dosed Every 8 Weeks as Maintenance Provides Durable Response in Adolescent Patients With Moderate-toSevere Atopic Dermatitis

Introduction: In the maintenance periods of ADvocate1 and ADvocate2, efficacy was consistent between the every 2 weeks and every 4 weeks (Q4W) maintenance dosing regimens, and a high proportion of Week 16 responders in the lebrikizumab withdrawal arm exhibited durable efficacy, suggesting less frequent dosing could maintain effectiveness in atopic dermatitis (AD). An extension to the ADjoin long-term study (ADjoin extension) subsequently evaluated the Q8W interval as a maintenance regimen. In the overall ADjoin extension population, Q8W has been reported to provide clinical responses consistent with Q4W dosing. As approximately 10% of adolescents have AD, this analysis describes whether adolescents in the ADjoin extension had a durable response over 32 weeks of Q4W or Q8W dosing. Methods: ADjoin extension was a 32-week study that enrolled patients with AD who had completed the 100-week long-term ADjoin study (NCT04392154) after participation in the parent studies. Key eligibility criteria included being adults or adolescents (≥12–<18 years at parent study baseline; weight ≥40 kg) and moderate-to-severe AD for ≥1 year at parent study entry. At ADjoin extension baseline, patients were re-randomized to receive open label lebrikizumab 250 mg Q4W or Q8W. The two primary endpoints were percentages of patients achieving ≥75% improvement (from parent study baseline) in Eczema Area and Severity Index (EASI 75) and Investigator’s Global Assessment score of 0/1 (IGA 0,1) at Week 32. Proportion of patients requiring concomitant treatment for AD was also reported. In this post-hoc analysis, a combined non-responder imputation and multiple imputation method was used for intercurrent events and missing data. Efficacy outcomes were summarized descriptively within each maintenance regimen. Results: Overall, 40 adolescent patients (Q4W, N=22; Q8W, N=18) enrolled in the 32-week extension. At extension baseline, 86.4% and 83.3% of Q4W and Q8W patients had an EASI 75 and 68.2% and 66.7% had an IGA (0,1), respectively. In both arms, mean response rates remained high through extension Week 32: percentages of patients (95% confidence interval) who met an EASI 75 were 81.8% (65.7%-97.9%) and 70.9% (49.4%-92.4%) in the Q4W and Q8W groups, respectively; 68.2% (48.7%-87.6%) and 63.1% (40.2%-86.0%) met an IGA (0,1). Six (27.3%) Q4W and seven (38.9%) Q8W patients required concomitant AD treatment. Conclusions: Lebrikizumab dosed every 4 or 8 weeks as maintenance provides durable response in adolescent patients with moderate to severe AD. The availability of Q4W and Q8W maintenance regimens for lebrikizumab provide clinicians with greater flexibility to individualize treatment for adolescents