Characterisation of the safety profile of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus: an integrated safety analysis

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 94; no. 1; pp. 1 - 9
• Main Authors: Montalban, Xavier, Wallace, Daniel, Genovese, Mark C, Tomic, Davorka, Parsons-Rich, Dana, Le Bolay, Claire, Kao, Amy H, Guehring, Hans
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.01.2023; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Antibodies; Arthritis, Rheumatoid - drug therapy; Autoimmune diseases; Clinical trials; Dose-Response Relationship, Drug; Double-Blind Method; Double-blind studies; Humans; IMMUNOLOGY; Lupus; Lupus Erythematosus, Systemic - drug therapy; Multiple Sclerosis; Multiple Sclerosis - drug therapy; Nervous system; Patients; Rheumatoid arthritis; RHEUMATOLOGY; SLE; Streptococcus infections; Treatment Outcome; IMMUNOLOGY; RHEUMATOLOGY; MULTIPLE SCLEROSIS; SLE
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp-2022-328799

ObjectiveAnalyse the integrated safety profile of evobrutinib, a Bruton’s tyrosine kinase inhibitor (BTKi), using pooled data from multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) trials.MethodsPhase II, randomised, double-blind, placebo-controlled trial data were analysed (N=1083; MS: n=213, 48 weeks (W); RA: n=390, 12W; SLE: n=480, 52W). The analysis included all patients who received ≥1 dose of evobrutinib (25 mg or 75 mg once daily, or 50 mg or 75 mgtwice daily) or placebo. Descriptive statistics and exposure-adjusted incidence rates (EAIR) were used to report treatment-emergent adverse events (TEAEs).ResultsData from 1083 patients were pooled: evobrutinib, n=861; placebo, n=271 (sum >1083 due to MS trial design: n=49 received both placebo (W0–24) and evobrutinib 25 mg (W25–48)); median follow-up time (pt-years): evobrutinib, 0.501; placebo, 0.463. Across indications, the proportion of patients with TEAEs and the EAIR were similar for evobrutinib and placebo (66.2% (247.6 events/100 pt-years) vs 62.4% (261.4 events/100 pt-years)). By indication, the EAIR (events/100 pt-years) of TEAEs for evobrutinib versus placebo were: MS: 119.7 vs 148.3; RA: 331.8 vs 306.8; SLE: 343.0 vs 302.1. Two fatal events occurred (in SLE). The serious infections EAIR was 2.7 and 2.1 events/100 pt-years for evobrutinib and placebo. For previously reported BTKi-class effects, the EAIR of transient elevated alanine aminotransferase/aspartate aminotransferase TEAEs (events/100 pt-years) with evobrutinib versus placebo was 4.8 vs 2.8/3.5 vs 0.7, respectively. IgG levels were similar in evobrutinib/placebo-treated patients.ConclusionsThis is the first BTKi-integrated safety analysis that includes patients with MS. Overall, evobrutinib treatment (all doses) was generally well tolerated across indications.Trial registration numbers NCT02975349, NCT03233230, NCT02975336.