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

Abstract

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.

Spesolimab: a comprehensive review on the anti‐IL‐36 receptor antibody in dermatology

“…Spesolimab did not show a significant difference in efficacy compared with placebo in a multicenter phase IIa randomized controlled trial on 51 patients with moderate‐to‐severe atopic dermatitis. Spesolimab was well tolerated, and no new clinically relevant adverse effects were reported 16 . Further development for atopic dermatitis was terminated.…”

“…15 Atopic dermatitis-related Staphylococcus aureus infection promotes cutaneous inflammation through the IL-36-mediated T-cell response. 16 Many studies have reported enhanced IL-36 activity in the lesional skin of atopic dermatitis but not to the extent seen in psoriasis. 17 The expression of IL-36 is higher in chronic AD lesions compared with acute lesions, suggesting the probable role of IL-36 in disease progression.…”

“…The common AEs (≥2 patients) observed were worsening atopic dermatitis, upper respiratory tract infections, nasopharyngitis, folliculitis, staphylococcal skin infection, headache, and nausea. 16 In the phase IIa, multicenter, double-blind, randomized, placebo-controlled pilot study of spesolimab for palmoplantar pustulosis, the drug was found to be well tolerated. Around 42.1% of patients in the spesolimab group had an investigator-defined drug-related AE through 32 weeks, mostly of mild to moderate severity.…”

“…Spesolimab was well tolerated, and no new clinically relevant adverse effects were reported. 16 Further development for atopic dermatitis was terminated.…”

“…Atopic dermatitis‐related Staphylococcus aureus infection promotes cutaneous inflammation through the IL‐36‐mediated T‐cell response 16 . Many studies have reported enhanced IL‐36 activity in the lesional skin of atopic dermatitis but not to the extent seen in psoriasis 17 .…”