Effect of Mirikizumab on Clinical and Endoscopic Outcomes Based on Prior Advanced Therapy Failure in Patients With Moderately to Severely Active Ulcerative Colitis

BACKGROUND: Mirikizumab demonstrated efficacy in moderately-to-severely active ulcerative colitis, including in patients with prior advanced therapy failure (PATF) (Phase 3: LUCENT-1 [NCT03518086], LUCENT-2 [NCT03524092]). This post hoc analysis evaluates mirikizumab efficacy by number/mechanism of PATF. METHODS: LUCENT-1 patients received 300 mg mirikizumab or placebo; mirikizumab induction responders entered LUCENT-2 and received 200 mg mirikizumab or placebo until week (W)52. Mirikizumab induction non-responders received extended induction with open-label 300 mg mirikizumab between W12 and W24. Extended induction responders received open-label 200 mg mirikizumab between W24 and W52. In each population, efficacy was analyzed by subgroups based on PATF number (0, 1, ≥ 2 [2-3]) and mechanism (including difficult-to-treat [DTT]: anti-TNF plus tofacitinib and/or vedolizumab). RESULTS: At baseline, 479/1162 patients (41.2%) had (≥ 1) PATF, of which 177 (37.0%) had DTT. Among mirikizumab-treated patients (n = 868), W12 clinical response was achieved by 69.8%, 63.9%, 45.3%, and 41.9% of the 0-PATF, 1-PATF, ≥ 2-PATF, and DTT subgroups, respectively. 42.1% (365/868) continued with maintenance treatment. Among W12 responders, 51.9% (0-PATF), 44.2% (1-PATF), 49.0% (≥ 2-PATF), and 42.9% (DTT) achieved clinical remission at W52. Over half of the patients (54.0% [147/272]) in the extended induction population had PATF; 51.0% (75/147) were DTT. At W24, clinical response was achieved by 62.4%, 41.4%, 49.5%, and 49.3% of the 0-PATF, 1-PATF, ≥ 2-PATF, and DTT subgroups. Of this 49.3% of the DTT subgroup (extended induction responders), 38.9% (14/36) achieved W52 clinical remission. CONCLUSIONS: Mirikizumab induction and maintenance is efficacious in moderately-to-severely active ulcerative colitis with or without prior failure of advanced therapy, including difficult-to-treat disease. TRAIL REGISTRATION: LUCENT-1: NCT03518086; LUCENT-2: NCT03524092.