To Örebro University

Introduction: Mirikizumab (MIRI), an anti-IL-23p19 antibody, has demonstrated efficacy and safety in adults with moderately-to-severely active ulcerative colitis (UC) in two Phase 3 trials (LUCENT-1/-2; NCT03518086, NCT03524092). As novel therapies for UC are not well studied in adults ≥60 years (older adults), we aimed to evaluate the efficacy and safety of MIRI compared to placebo (PBO) during induction and maintenance treatment among this especially vulnerable subgroup of patients with UC.

Methods: In LUCENT-1, patients with UC were randomized to receive 3 intravenous (IV) doses of 300mg MIRI or PBO every four weeks (Q4W) at W0, W4, and W8. In LUCENT-2, responders to MIRI induction at W12 were re-randomized to subcutaneous (SC) 200mg MIRI or PBO Q4W for another 40 weeks (until W52 of continuous treatment). Endpoints evaluated in this post-hoc analysis included clinical response, clinical remission, symptomatic remission, endoscopic remission, corticosteroid (CS)-free remission (W52 only), histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR), and bowel urgency (clinically meaningful improvement and remission). Efficacy in the subgroup of older adults was assessed at W12 and W52 using Fisher’s Exact tests. Safety data were summarized among patients aged 60 and older who received at least one dose of study treatment.

Results: At LUCENT-1 baseline, 13.3% of patients (n=154/1162) were ≥60 years, with a median age of 65 [Quartile (Q)1: 62.0, Q3: 69]. Apart from higher prevalence of comorbidities, longer disease duration, older age at diagnosis, and lower frequency of concomitant treatment with thiopurines, the baseline demographics and characteristics were similarto the overall patient population, including disease activity (per modified Mayo Score and Mayo Endoscopic Subscore), disease extent, and prior advanced therapy failure. At W12 and W52, a significantly greater proportion of older adults treated with MIRI vs. PBO achieved clinical response and symptomatic remission. While the studies were not powered to detect differences between MIRI and PBO in this subgroup, there were numerically higher response rates for MIRI vs. PBO for all other outcomes. The safety profile for MIRI in older patients was consistent with the overall study population. There were no deaths and no discontinuations due to adverse events among MIRI-treated older adults.

Conclusion: Mirikizumab induced and maintained clinical response and was well tolerated in patients 60 years of age and older with moderately-to-severely active UC.