Lebrikizumab Confirms a Consistent Safety Profile in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis: Data From 11 Trials With Over 3000 Patient-Years of Exposure

Introduction: We provide updated long-term safety data for lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis (AD). Methods: Integrated data from 11 phase 2/3 clinical trials were summarized in 2 datasets: 1) All-placebo-controlled Week 0-16 (All-PC; lebrikizumab 250 mg every 2 weeks [LEBQ2W] vs placebo); and 2) All-LEB (includes patients who received ≥1 dose of lebrikizumab any time during the 11 studies). All-PC includes phase 3 studies ADvocate 1 and 2, ADhere, ADhere-J, ADopt-VA, and ADvantage, and phase 2b KGAF; All-LEB includes phase 3 ADore and ADjoin and phase 2 Treble and KGAH, in addition to those in All-PC. Percentage and exposure-adjusted incidence rates (IR)/100 patient-years exposure are provided for All-PC and All-LEB, with study-size adjusted for All-PC. Results: In All-PC, there were 719 patients (205.9 PYE) in the placebo group and 1251 (375.8 PYE) in the LEBQ2W group. All-LEB had 2415 patients (3167.8 PYE). In All-PC, the frequency of treatment-emergent adverse events (TEAEs) was similar between treatment groups; most were nonserious and mild/moderate in severity and did not lead to treatment discontinuation. Frequencies of SAEs were low in All-PC (placebo, 1.7%; LEBQ2W, 1.2%), and IR decreased with longer lebrikizumab exposure (IR LEBQ2W in All-PC, 3.9; IR All-LEB, 2.9). One death was reported in the placebo group in All-PC and 4 deaths in All-LEB (no deaths were considered related to the study drug by investigators). The most frequently reported TEAE (Preferred Terms) in All-PC was atopic dermatitis (12.8%) for placebo and conjunctivitis (7.1%) for LEBQ2W. In the placebo-controlled period, frequencies of the following AEs were: conjunctivitis cluster (placebo, 3.0%; LEBQ2W, 11.7%), injection site reactions (placebo, 1.6%; LEBQ2W, 2.9%); and herpes zoster (placebo, 0.1%; LEBQ2W, 0.4%). Skin infections were reported less frequently with lebrikizumab (placebo, 6.0%; LEBQ2W, 2.4%). The IRs of the AEs of special interest decreased (conjunctivitis cluster, injection site reactions) or remained stable (herpes zoster) with increased exposure years to lebrikizumab. Conclusion: Results of this updated integrated safety analysis are consistent with previously reported data1 from the lebrikizumab clinical trial program. IRs of most TEAEs did not increase with longer duration of exposure to lebrikizumab in adolescents and adults with AD.