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.