Long-Term Safety of Mirikizumab in Patients With Moderately to Severely Active Ulcerative Colitis: An Integrated 2-Year Safety Analysis.

Abstract

Ulcerative colitis (UC) is a chronic immune-mediated disease requiring ongoing treatment to maintain remission. This report presents the 2-year safety outcomes of mirikizumab, a humanized immunoglobulin G4 anti-interleukin-23p19 monoclonal antibody, in moderately to severely active UC from phase 3 studies LUCENT-1 (NCT03518086), LUCENT-2 (NCT03524092), and LUCENT-3 (NCT03519945). Patients who underwent induction (LUCENT-1) and maintenance (LUCENT-2), and entered long-term maintenance (LUCENT-3) were assessed in 2 cohorts: induction responders and extended-induction responders. Both cohorts underwent up to 104 weeks of continuous treatment with mirikizumab. Adverse events (AEs) were assessed in these 2 cohorts and within subsets of patients aged 60 years or older and patients using corticosteroids, immunomodulators, or both at baseline. Safety was generally consistent across induction responders (N = 333) and extended-induction responders (N = 149) and across patient subsets. Nasopharyngitis, COVID-19, arthralgia, UC (worsening/reoccurrence of symptoms), and headache were the most common AEs. Serious AEs were reported in less than 10% of both cohorts. Infections (mostly mild), cerebrocardiovascular events, and malignancies occurred in 47.4% and 49.7%, 0.9% and 1.3%, and 0% and 3.4% of induction responders and extended-induction responders, respectively. Injection-site reactions (induction responders: 10.2% and extended-induction responders: 8.1%) declined over time. Safety profiles in patient subsets and in the whole population were similar, except for hypertension, which was more frequent in patients aged 60 years or older. The mirikizumab 2-year integrated safety profile in patients with moderately to severely active UC was consistent across subgroups and with previous findings, without new significant safety concerns.