Sustained Efficacy Following Treatment With Lebrikizumab

Atopic Dermatitis

A subset of moderate-to-severe atopic dermatitis (AD) patients who were randomly withdrawn from lebrikizumab maintained a stable EASI 90 response up to Week 52 with negligible remaining lebrikizumab serum concentrations, according to research presented at the Revolutionizing Atopic Dermatitis (RAD) Conference from June 8-10 in Chicago, Illinois.

Jonathan I. Silverberg, MD, PhD, MPH, and colleagues presented “EASI 90 response sustained up to 38 weeks after lebrikizumab withdrawal despite negligible serum concentrations,” detailing a post-hoc analysis of the Phase 3 Advocate 1 (NCT04146363) and Advocate 2 (NCT04178967) studies. The study was performed to better understand the relationship between lebrikizumab serum concentration levels and sustained clinical response in a subpopulation of lebrikizumab responders who discontinued treatment after completion at 16 weeks.

Lebrikizumab had already demonstrated robust efficacy as monotherapy for moderate-to-severe AD in the two Phase 3, randomized, double-blind, placebo-controlled, 52-week trials (Silverberg, et al. N Engl J Med 2023;388:1080-91; Blauvelt, et al. Br J Dermatol 2023; 188:740–748). Among lebrikizumab responders at the end of the 16-Week induction period, EASI 75 was maintained in 82% of patients treated with continuous lebrikizumab every 4 weeks (Q4W) and by 66% of the patients in the lebrikizumab withdrawal arm at Week 52.

The new study showed that 17 of the 60 lebrikizumab responders (28%) who were withdrawn from treatment maintained EASI 90 for 80% of the visits during the 38-week withdrawal period, achieved EASI 90 at Week 52, and did not use rescue medication. Withdrawal-period pharmacokinetic data were available from 16 of these 17 patients. At Week 16, the mean (SD) serum lebrikizumab concentration was 92.4 (29.9) μg/mL. The mean (SD) serum concentrations decreased to 7.3 (14.0) μg/mL at Week 32 and 0.15 (0.20) μg/mL at Week 52, representing 92% and >99% reductions, respectively. At Week 52, 12 of the 16 patients had serum concentrations below the lower level of quantification (LLOQ: 0.09 μg/mL) for the clinical assay. In the popPK analysis, the mean elimination half-life for lebrikizumab was approximately 24.5 days. Lebrikizumab, therefore, had undergone approximately 5 half-lives at Week 32 and 10.9 half-lives at Week 52; the presenters noted that 5 to 7 half-lives for a biologic are often considered for a washout period (Evans. J Exp Stroke Transl Med 2010; 9:8-18).

“This is the first analysis that could provide additional insights into lebrikizumab therapy-free remission,” the presenters concluded. “Further studies are needed to identify and characterize this subpopulation of AD patients and lebrikizumab’s potential disease-modifying properties.”

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