Long-term management of moderate-to-severe atopic dermatitis with lebrikizumab and concomitant topical corticosteroids: a 68-week randomized double-blind placebo-controlled phase III trial in Japan (ADhere-J)

Abstract Background Moderate-to-severe atopic dermatitis (AD) affects the quality of life of patients. More treatment options are urgently needed to manage this chronic disease. Lebrikizumab is a monoclonal antibody that binds to interleukin-13, a key mediator in AD pathogenesis. In Japanese patients, lebrikizumab has been evaluated through week 16 in the randomized placebo-controlled phase III ADhere-J study. Objectives To evaluate the long-term efficacy and safety of lebrikizumab in combination with topical corticosteroids (TCS) in the ADhere-J study. Methods Patients aged ≥12 years weighing ≥ 40 kg with moderate-to-severe AD and receiving either subcutaneous lebrikizumab 250 mg ­every 2 weeks (Q2W)/every 4 weeks (Q4W) or placebo during the 16-week induction period were evaluated during the long-term maintenance period from week 16 to week 68. Responders achieved the co-primary endpoints at week 16: an Investigator’s Global Assessment score of 0 or 1 [IGA (0,1)] with ≥ 2-point improvement from baseline and/or ≥ 75% improvement from baseline in Eczema Area and Severity Index (EASI 75). In this analysis, week 16 responders received lebrikizumab 250 mg Q2W or Q4W combined with TCS during the maintenance period (maintenance primary population; MPP); week 16 per-protocol nonresponders received lebrikizumab Q2W with TCS (maintenance escape population; MEP). Major endpoints included IGA (0,1) with ≥ 2-point improvement from baseline and EASI 75 through week 68. Other outcomes included quality of life, itch and serum thymus and activation-regulated chemokine. The trial was registered with ClinicalTrials.gov (NCT04760314). Results At week 68, 66–81% of 103 patients in the MPP and 32–38% of 168 patients in the MEP achieved IGA (0,1) with ≥ 2-point improvement from baseline. EASI 75 was maintained by 83–89% of patients in the MPP, while 71–80% of patients in the MEP achieved this outcome by week 68. Across treatment arms, patients in the MPP tended to maintain improvements recorded at week 16, while patients in the MEP steadily improved across the maintenance period. No new safety signals were reported, and most treatment-emergent adverse events were mild or moderate in severity in both populations. Safety outcomes were consistent with previous reports for lebrikizumab treatment in global studies. Conclusions These results support the use of lebrikizumab in combination with TCS for the treatment of moderate-to-severe AD in the Japanese population in the long term.