Sands Bruce E, D'Haens Geert, Clemow David B, Irving Peter M, Johns Jordan T, Gibble Theresa Hunter, Abreu Maria T, Lee Scott D, Hisamatsu Tadakazu, Kobayashi Taku, Dubinsky Marla C, Vermeire Severine, Siegel Corey A, Peyrin-Biroulet Laurent, Moses Richard E, Milata Joe, 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 Oct 25. doi: 10.1093/ibd/izae253.
Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152.
Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance. Of these, 324 completed week 52 and 316 entered extension treatment (286 week 52 responders; 179 week 52 remitters). Efficacy and safety outcomes are reported for mirikizumab-treated LUCENT-3 participants, including biologic-failed patients, with data for week 52 maintenance responders/remitters. Discontinuations or missing data were handled by nonresponder imputation, modified nonresponder imputation (mNRI), and observed cases.
Using mNRI, 81.6% of week 52 responders demonstrated clinical response at week 152. Week 152 remission rates for week 52 responders included clinical (56.1%), corticosteroid-free (CSF; 54.5%), endoscopic (61.0%), histologic-endoscopic mucosal remission (HEMR; 52.6%), symptomatic (74.9%), and bowel urgency (BU; 58.6%). At week 152, 53.3% of week 52 responders achieved histologic-endoscopic mucosal improvement (HEMI) and 74.3% achieved BU clinically meaningful improvement (CMI). Among week 52 remitters, 85.4% showed a clinical response at week 152, with clinical (70.1%), CSF (68.9%), endoscopic (72.0%), HEMR (63.4%), symptomatic (81.4%), and BU (60.8%) remission. At week 152, among week 52 remitters, 64.0% of patients achieved HEMI and 75.6% achieved BU CMI. Stool frequency, rectal bleeding, BU, and abdominal pain score reductions from induction baseline to maintenance week 52 were sustained through week 152 for week 52 completers. Overall, in the safety population, 7.4% of patients reported severe adverse events (AEs); 5.3% discontinued treatment due to AEs. AEs of special interest included opportunistic infection (1.8%), hepatic disorders (3.2%), cerebrocardiovascular events (1.5%), and malignancy (0.3%). Patients with antidrug antibodies reduced over time from 23.6% in year 1 to 3.2% in year 3.
Symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes support long-term sustained benefit of mirikizumab treatment up to 152 weeks in patients with UC, including biologic-failed patients, with no new safety concerns.
ClinicalTrials.gov: NCT03518086; NCT03524092; NCT03519945.
Mirikizumab是一种靶向p19的白细胞介素-23单克隆抗体，已证明在中度至重度活动性溃疡性结肠炎（UC）患者中，第12周可诱导临床缓解，并维持至第104周。本文展示了LUCENT-3开放标签扩展研究至第152周的结果。
在868例接受Mirikizumab治疗诱导的LUCENT临床试验项目患者中，544例有反应，其中365例重新随机分组接受Mirikizumab维持治疗。其中，324例完成了第52周治疗，316例进入扩展治疗（286例第52周有反应者；179例第52周缓解者）。报告了接受Mirikizumab治疗的LUCENT-3参与者的疗效和安全性结果，包括生物制剂治疗失败的患者，并提供了第52周维持治疗有反应者/缓解者的数据。停药或缺失数据通过无反应者插补、改良无反应者插补（mNRI）和观察病例进行处理。
使用mNRI，81.6%的第52周有反应者在第152周表现出临床反应。第52周有反应者的第152周缓解率包括临床缓解（56.1%）、无皮质类固醇缓解（CSF；54.5%）、内镜缓解（61.0%）、组织学-内镜黏膜缓解（HEMR；52.6%）、症状缓解（74.9%）和排便急迫缓解（BU；58.6%）。在第152周，52周有反应者中有53.3%实现了组织学-内镜黏膜改善（HEMI），74.3%实现了排便急迫临床意义改善（CMI）。在第52周缓解者中，85.4%在第152周表现出临床反应，临床缓解（70.1%）、CSF缓解（68.9%）、内镜缓解（72.0%）、HEMR缓解（63.4%）、症状缓解（81.4%）和BU缓解（60.8%）。在第152周，第52周缓解者中有64.0%的患者实现了HEMI，75.6%实现了排便急迫CMI。对于第52周完成治疗者，从诱导期基线到维持治疗第52周的粪便频率、直肠出血、排便急迫和腹痛评分降低在第152周仍持续存在。总体而言，在安全人群中，7.4%的患者报告了严重不良事件（AE）；5.3%因AE停药。特别关注的AE包括机会性感染（1.8%）、肝脏疾病（3.2%）、心脑血管事件（1.5%）和恶性肿瘤（0.3%）。抗药物抗体阳性的患者随时间减少，从第1年的23.6%降至第3年的3.2%。
症状、临床、内镜、组织学和生活质量结果支持Mirikizumab治疗UC患者长达152周的长期持续获益，包括生物制剂治疗失败的患者，且无新的安全问题。
ClinicalTrials.gov：NCT03518086；NCT03524092；NCT03519945。
