Spesolimab, an anti-interleukin-36 receptor antibody, in patients with moderate-to-severe atopic dermatitis: Results from a multicentre, randomized, double-blind, placebo-controlled, phase IIa study.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, and there is increasing evidence that the interleukin (IL)-36 pathway may play a role in the pathogenesis of AD. OBJECTIVES: To evaluate the efficacy and safety of spesolimab, a novel anti-IL-36 receptor antibody, in adult patients with moderate-to-severe AD. METHODS: In this phase IIa study, 51 eligible patients were randomized 2:1 to receive intravenous doses of spesolimab 600 mg or placebo every 4 weeks. The primary endpoint was the percentage change from baseline in Eczema Area and Severity Index (EASI) score at Week 16. RESULTS: The decrease in EASI score from baseline to Week 16 was -37.9% for spesolimab versus -12.3% for placebo (adjusted mean difference -25.6%, p = 0.149). A predefined sensitivity analysis, excluding data from patients who used restricted corticosteroids, resulted in an adjusted mean difference of -48.3% (nominal p = 0.024). Spesolimab was well tolerated, with no clinically relevant safety signals. CONCLUSIONS: This is the first study to evaluate the IL-36 pathway inhibition in AD. Although not statistically significant, numerical improvements were observed in the primary endpoint of change from baseline in the EASI score. Spesolimab had an acceptable safety profile, with no unexcepted safety concerns.