Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis
Authors: Simpson Eric L. , Gooderham Melinda , Wollenberg Andreas , Weidinger Stephan , Armstrong April , Soung Jennifer , Ferrucci Silvia , Lima Renata Gontijo , Witte Michael M. , Xu Wen , ElMaraghy Hany , Natalie Chitra R. , Pierce Evangeline , Blauvelt Andrew ,   ADhere Investigators, Jarell Abel , Sadick Neil , Sofen Howard , Wallace Paul W , Carpio Jose M , Greenstein David , Moore Angela , Mendez Jose M , Guenthner Scott T , McFalda Wendy L , Laquer Vivian T , Forman Seth , Schlesinger Todd , Blauvelt Andrew , Crowley Jeffrey J , Tan Ricardo , Averill Francis J , George Rosalyn E , Armas Eddie , Lockshin Benjamin , Soung Jennifer , Nahm Walter K , Ehrlich Alison A , Dhawan Sunil S , Simpson Eric L , Sitar Steve , Bagel Jerry , Rich Phoebe , Torkan Bruce , Fivenson David F , Weisman Jamie D , Stone Melody L , Armstrong April , Saifi Mirwais , Glick Brad P , Gooderham Melinda , Day Isaiah , Albrecht Lorne , Wiseman Marni , Gratton David , Hong Chi-Ho , Majorek-Olechowska Bernadetta , Reich Adam , Krecisz Beata , Walecka-Herniczek Irena , Weglowska Jolanta , Bergler-Czop Beata , Cimoszko Boguslawa , Padlewska Kamila , Czubek Maria , Pinter Andreas , Reich Kristian , Wildfeuer Thomas , Aschoff Roland 
Published: January 2023

ImportanceLebrikizumab (LEB), a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD) during 16 weeks of monotherapy in a phase 2b trial, and two 52-week phase 3 trials.ObjectiveTo evaluate efficacy and safety of LEB combined with low- to mid-potency topical corticosteroids (TCS) in patients with moderate-to-severe AD.Design, Setting, and ParticipantsThe ADhere trial was a 16-week randomized, double-blinded, placebo (PBO)-controlled, multicenter, phase 3 clinical trial conducted from February 3, 2020, to September 16, 2021. The study was conducted at 54 outpatient sites across Germany, Poland, Canada, and the US and included adolescent (aged ≥12 to &amp;lt;18 years weighing ≥40 kg) and adult patients with moderate-to-severe AD. The treatment allocation ratio was 2:1 (LEB:PBO).InterventionsOverall, 211 patients were randomized to subcutaneous LEB (loading dose of 500 mg at baseline and week 2, followed by 250 mg every 2 weeks [Q2W] thereafter) or PBO Q2W in combination with TCS for 16 weeks.Main Outcomes and MeasuresEfficacy analyses at week 16 included proportions of patients achieving Investigator’s Global Assessment score of 0 or 1 (IGA [0,1]) with 2 or more points improvement from baseline, and 75% improvement in the Eczema Area and Severity Index (EASI-75). Key secondary end points included evaluation of itch, itch interference on sleep, and quality of life. Safety assessments included monitoring adverse events (AEs).ResultsThe mean (SD) age of patients was 37.2 (19.3) years, 103 (48.8%) patients were women, 31 (14.7%) patients were Asian, and 28 (13.3%) patients were Black/African American. At week 16, IGA (0,1) was achieved by 145 (41.2%) patients in the LEB+TCS group vs 66 (22.1%) receiving PBO+TCS (P = .01); corresponding proportions of patients achieving EASI-75 were 69.5% vs 42.2% (P &amp;lt; .001). The LEB+TCS group showed statistically significant improvements in all key secondary end points. Most treatment-emergent adverse events (TEAEs) were nonserious, mild or moderate in severity, and did not lead to study discontinuation. The TEAEs frequently reported in the LEB+TCS group included conjunctivitis (7 [4.8%]), headache (7 [4.8%]), hypertension (4 [2.8%]), injection site reactions (4 [2.8%]), and herpes infection (5 [3.4%]) vs 1.5% or less patient-reported frequencies in the PBO+TCS group. Similar frequencies of patient-reported serious AEs following LEB+TCS (n = 2, 1.4%) and PBO+TCS (n = 1, 1.5%).Conclusions and RelevanceIn this randomized phase 3 clinical trial, LEB+TCS was associated with improved outcomes in adolescents and adults with moderate-to-severe AD compared with TCS alone, and safety was consistent with previously reported AD trials.Trial RegistrationClinicalTrials.gov Identifier: NCT04250337