Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn's Disease
Endoscopic, Radiologic, and Histologic Healing With Vedolizumab in Patients With Active Crohn's Disease
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DOI：
10.1053/j.gastro.2019.06.038
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发表时间：
2019-10-01
期刊：
影响因子：
29.4
通讯作者：
Feagan, Brian G.
中科院分区：
文献类型：
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作者：
Danese, Silvio;Sandborn, William J.;Feagan, Brian G.
背景与目的：Vedolizumab是一种用于治疗中度至重度活动性克罗恩病（CD）的肠道选择性单克隆抗体。我们对接受维多单抗治疗的乳糜泻患者的内窥镜、放射学和组织学愈合进行了前瞻性研究。方法：我们在2015年3月至2017年12月期间对101例至少3个月活动性CD （CD活动指数[CDAI]评分为220-450，CD [SES-CD]评分为7或以上，1个或更多粘膜溃疡[由内窥镜确定]，常规治疗失败）的患者进行了一项3b期，开放标签单组研究。在纳入的患者中，54.5%的患者既往有1种或1种以上肿瘤坏死因子（TNF）拮抗剂治疗失败，44.6%的患者在基线时有严重的内窥镜疾病活动性（SES-CD评分高于15）。参与者在第0,2和6周接受vedolizumab （300mg静脉注射），然后每8周一次，持续26周（主要研究）或52周（亚研究，56例患者）。第26周的主要终点是内镜缓解（SES-CD评分为4分或更低）；其他终点包括内镜反应（SES-CD减少50%）、放射学缓解（磁共振活动指数评分低于7）和组织学反应（修改后的总体组织学疾病活动评分为4或更低）。结果：在第26周，11.9%的患者在内镜下缓解（95%可信区间[CI] 6.3-9.8）；在第52周，17.9%的患者内镜缓解（95% CI 8.9-30.4）。在第26周和第52周，首次使用TNF拮抗剂的患者比TNF拮抗剂失效的患者获得内窥镜缓解的比例更高。中度CD患者（SES-CD评分为7-15）在26周和52周内窥镜缓解的比例高于重度CD患者（SES-CD评分高于15）。粘膜完全愈合的患者比例随着时间的推移而增加，结肠的愈合率高于回肠。在第26周，21.9%的患者通过磁共振肠造影（95% CI 9.3-40.0）和38.1%的患者在第52周（95% CI 18.1-61.6）检测到缓解。在第26周，24.4%的患者在结肠有组织学反应（95% CI 15.3-35.4）， 28.3%的患者在回肠有组织学反应（95% CI 17.5-41.4）。在第52周，20.5%的患者在结肠有组织学反应（95% CI 9.8-35.3）， 34.3%的患者在回肠有组织学反应（95% CI 19.1-52.2）。没有明显的安全性问题，包括肠外症状的恶化。结论：在一项3b期试验中，我们发现26周和52周的vedolizumab治疗（300mg，在第0、2和6周，之后每8周）可诱导中重度活动性CD患者的内镜、放射学和组织学愈合。
BACKGROUND & AIMS: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy. METHODS: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017. Among the patients enrolled, 54.5% had previous failure of 1 or more tumor necrosis factor (TNF) antagonists and 44.6% had severe endoscopic disease activity (SES-CD scores above 15) at baseline. Participants received vedolizumab (300 mg intravenously) at weeks 0, 2, and 6, and then every 8 weeks thereafter, for 26 weeks (primary study) or 52 weeks (substudy, 56 patients). The primary endpoint at week 26 was endoscopic remission (SES-CD score of 4 or less); other endpoints included endoscopic response (50% reduction in SES-CD), radiologic remission (magnetic resonance index of activity score below 7), and histologic response (modified global histologic disease activity score of 4 or less). RESULTS: At week 26, 11.9% of patients were in endoscopic remission (95% confidence interval [CI] 6.3-9.8); at week 52, 17.9% of the patients were in endoscopic remission (95% CI 8.9-30.4). Higher proportions of patients naive to TNF antagonists achieved endoscopic remission than patients with TNF-antagonist-failure at weeks 26 and 52. Higher proportion of patients with moderate CD (SES-CD scores, 7-15) achieved endoscopic remission at weeks 26 and 52 than patients with severe CD (SES-CD scores above 15). The proportion of patients with complete mucosal healing increased over time, with greater rates of healing in the colon than in the ileum. Remission was detected by magnetic resonance enterography in 21.9% of patients at week 26 (95% CI 9.3-40.0) and in 38.1% at week 52 (95% CI 18.1-61.6). At week 26, 24.4% of patients had a histologic response in the colon (95% CI 15.3-35.4) and 28.3% of patients had a histologic response in the ileum (95% CI 17.5-41.4). At week 52, 20.5% of patients had a histologic response in the colon (95% CI 9.8-35.3) and 34.3% of patients had a histologic response in the ileum (95% CI 19.1-52.2). There were no notable safety issues, including worsening of extraintestinal manifestations. CONCLUSIONS: In a phase 3b trial, we found that 26 and 52 weeks of treatment with vedolizumab (300 mg, at weeks 0, 2, and 6, and then every 8 weeks thereafter) induces endoscopic, radiologic, and histologic healing in patients with moderately to severely active CD.