Efficacy and safety of lebrikizumab combined with topical corticosteroids in Japanese patients with moderate-to-severe atopic dermatitis: a phase 3, double-blind, placebo-controlled, randomized clinical trial (ADhere-J)

Objective: To evaluate efficacy and safety of lebrikizumab combined with topical corticosteroids (TCS) in Japanese patients with moderate-to-severe atopic dermatitis (AD). Methods: Phase 3, randomized, double-blind, placebo-controlled study (ADhere-J; NCT04760314) conducted at 37 centers in Japan (March 2021-February 2023), comprising 16-week induction (reported herein) and 52-week maintenance periods. Overall, 286 patients aged >= 12 years and >= 40 kg were randomized (interactive web response system) to subcutaneous placebo, lebrikizumab 250 mg every 4 weeks (Q4W), or lebrikizumab 250 mg every 2 weeks (Q2W) with TCS (82, 81, and 123 patients, respectively). Coprimary endpoints were proportions of patients achieving (1) Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with >= 2-point improvement from baseline, and (2) >= 75% improvement from baseline in Eczema Area and Severity Index (EASI 75) at week 16. Results: At week 16, compared with placebo, a significantly greater proportion of the lebrikizumab Q4W and Q2W groups achieved IGA (0,1) (6.1% vs. 29.1% and 33.4%, respectively; both p < 0.001) and EASI 75 (13.4% vs. 47.2% and 51.2%, respectively; both p < 0.001). Serious adverse events (AEs) occurred in 2.4%, 0%, and 0.8% of placebo, lebrikizumab Q4W and Q2W groups, respectively. Common treatment-emergent AEs, including pyrexia (placebo: 15.9%; lebrikizumab Q4W/Q2W: 18.5%/20.3%), conjunctivitis allergic (placebo: 4.9%; lebrikizumab Q4W/Q2W: 12.3%/17.1%), and conjunctivitis (placebo: 2.4%; lebrikizumab Q4W/Q2W: 6.2%/9.8%), were more frequent with lebrikizumab; most were mild or moderate. Conclusion: Consistent with global data, lebrikizumab demonstrated clinical improvements with a positive benefit-risk profile in Japanese adults and adolescents with moderate-to-severe AD through 16 weeks.