Sands Bruce E, D'Haens Geert, Clemow David B, Irving Peter M, Johns Jordan T, Hunter Gibble Theresa, Abreu Maria T, Lee Scott, Hisamatsu Tadakazu, Kobayashi Taku, Dubinsky Marla C, Vermeire Severine, Siegel Corey A, Peyrin-Biroulet Laurent, Moses Richard E, Milata Joe, Arora Vipin, Panaccione Remo, Dignass Axel
Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Inflamm Bowel Dis. 2024 Dec 5;30(12):2245-2258. doi: 10.1093/ibd/izae024.
Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at week 12 (W12) and maintaining clinical remission at W52 in patients with moderately to severely active ulcerative colitis. Results are presented from the open-label extension study through W104.
Clinical, symptomatic, quality-of-life, and adverse event outcomes are reported for mirikizumab induction responders and extended induction responders, including biologic-failed patients, who entered LUCENT-3, with data shown for W52 maintenance responders or remitters. Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC).
Among W52 mirikizumab responders, clinical response at W104 was 74.5%, 87.2%, and 96.7% and clinical remission was 54.0%, 62.8%, and 70.1% for NRI, mNRI, and OC, respectively. Among W52 mirikizumab remitters, clinical response at W104 was 76.6%, 89.0%, and 98.3% and clinical remission was 65.6%, 76.1%, and 84.2%. Using mNRI, remission rates at W104 for W52 clinical remitters were 74.7% corticosteroid-free, 79.5% endoscopic, 63.9% histologic-endoscopic mucosal remission, 85.9% symptomatic, 59.8% bowel urgency, 80.5% Inflammatory Bowel Disease Questionnaire (using NRI), 71.2% histologic-endoscopic mucosal improvement, and 77.5% bowel urgency improvement. Previous biologic-failed vs not-biologic-failed patient data were generally similar. Extended induction mNRI clinical response was 81.9%. Serious adverse events were reported in 5.2% of patients; 2.8% discontinued treatment due to adverse events.
Endoscopic, histologic, symptomatic, and quality-of-life outcomes support the long-term benefit of mirikizumab treatment up to 104 weeks in patients with ulcerative colitis, including biologic-failed patients, with no new safety concerns.
Mirikizumab是一种靶向p19的白细胞介素-23单克隆抗体，在中度至重度活动性溃疡性结肠炎患者中，可有效诱导第12周（W12）临床缓解，并维持第52周临床缓解。本文展示了该药物开放标签扩展研究至第104周的结果。
报告了Mirikizumab诱导缓解者和扩展诱导缓解者（包括生物制剂治疗失败的患者）的临床、症状、生活质量和不良事件结局，这些患者进入了LUCENT-3研究，并展示了第52周维持缓解者或疾病缓解者的数据。停药或缺失数据采用无应答者推算（NRI）、改良无应答者推算（mNRI）和观察病例（OC）方法处理。
在第52周Mirikizumab缓解者中，第104周的临床缓解率分别为：NRI法74.5%、mNRI法87.2%、OC法96.7%；临床缓解率分别为：NRI法54.0%、mNRI法62.8%、OC法70.1%。在第52周Mirikizumab疾病缓解者中，第104周的临床缓解率分别为：76.6%、89.0%、98.3%；临床缓解率分别为：65.6%、76.1%、84.2%。采用mNRI法，第104周第52周临床缓解者的缓解率为：无皮质类固醇缓解率74.7%、内镜缓解率79.5%、组织学-内镜黏膜缓解率63.9%、症状缓解率85.9%、排便急迫缓解率59.8%、炎症性肠病问卷缓解率80.5%（采用NRI法）、组织学-内镜黏膜改善率71.2%、排便急迫改善率77.5%。既往生物制剂治疗失败与未失败患者的数据总体相似。扩展诱导mNRI临床缓解率为81.9%。5.2%的患者报告了严重不良事件；2.8%的患者因不良事件停药。
内镜、组织学、症状和生活质量结局支持Mirikizumab治疗溃疡性结肠炎患者长达104周的长期获益，包括生物制剂治疗失败的患者，且无新的安全问题。
