Safety and tolerability of spesolimab in patients with ulcerative colitis

Background: Interleukin (IL)-36 signaling has been shown to be increased in ulcerative colitis (UC). Spesolimab, a novel humanized monoclonal antibody, targets the IL-36 pathway. Research Design and Methods: We report safety, immunogenicity, and efficacy data of intravenous (IV) spesolimab in UC. Study 1: phase II, randomized, placebo-controlled trial (300 mg single dose; 450 mg every 4 weeks [q4w]; or 1,200 mg q4w, three doses). Study 2: phase IIa, randomized, placebo-controlled trial (1,200 mg q4w). Study 3: phase IIa, open-label, single-arm trial (1,200 mg q4w). Studies lasted 12 weeks, with a 12-, 24-, and 16-week safety follow-up, respectively. Results: Adver+se event (AE) rates were similar for spesolimab and placebo in Studies 1 (N = 98; 64.9%; 65.2%) and 2 (N = 22; 86.7%; 71.4%); all patients in Study 3 (N = 8) experienced AEs. The most frequent investigator-assessed drug-related (spesolimab; placebo) AEs were skin rash (5.4%; 0%) and nasopharyngitis (4.1%; 0%) in Study 1; acne (13.3%; 0%) in Study 2; one patient reported skin rash, nasopharyngitis, headache, and acne in Study 3. Efficacy endpoints were not met. Conclusions: Spesolimab was generally well tolerated, with no unexpected safety concerns. The safety data are consistent with studies in other inflammatory diseases.