Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada.
Alimentiv, Inc., London, Ontario, Canada.
Inflamm Bowel Dis. 2023 Jun 1;29(6):866-874. doi: 10.1093/ibd/izac149.
With the expanding therapeutic armamentarium for inflammatory bowel disease (IBD), real-world data may help inform drug positioning. We assessed clinical, endoscopic, imaging, and biochemical response/remission outcomes in patients with Crohn's disease (CD) treated with ustekinumab in a large Canadian IBD center.
A retrospective cohort study of CD patients was treated with ustekinumab. Clinical, endoscopic, radiological, and biochemical response and remission outcomes were stratified by prior biologic exposure status. Hazard ratios for biologic exposure status were estimated using Cox proportional hazard models and subgroup-specific incidence rates for healing.
A total of 231 patients (55.9% female, median 45.8 years) were identified as receiving ustekinumab during the study period, with 2 patients subsequently excluded (N = 229). Of these patients, 79.0% (181 of 229) were bio-experienced, with 38.7% (70 of 181) having failed 1 biologic and 61.3% (111 of 181) having failed ≥2 biologics. At 3 months of follow-up after induction, clinical remission (Harvey-Bradshaw Index ≤4) was achieved by 59.1% (62 of 105) of bio-experienced patients and 79.4% (27 of 34) of bio-naïve patients (relative risk [RR], 1.34; 95% CI, 1.06-1.70; P = .013). Endoscopic remission (absence of mucosal ulcers) was achieved in 37.9% (33 of 87) cases. Rate of endoscopic healing (either endoscopic response or remission) per 1000 person-months was 72.7 (95% CI, 42.4-125.1) and 50.2 (37.9-66.4); and the median time to endoscopic response was 8.4 months (95% CI, 6.4-9.8) and 15.4 months (95% CI, 10.3-17.9) in bio-naïve vs bio-experienced patients, respectively. Imaging response/remission and steroid-free remission rates were higher in bio-naïve patients.
In this large real-world cohort of CD patients with complex phenotypes and high rates of prior biologic exposure, we observed that ustekinumab was effective and safe with higher rates of improvement in bio-naïve subjects across a range of end points.
随着炎症性肠病（IBD）治疗方法的不断增加，真实世界的数据可能有助于确定药物定位。我们评估了在加拿大一个大型 IBD 中心接受乌司奴单抗治疗的克罗恩病（CD）患者的临床、内镜、影像学和生化反应/缓解结果。
对接受乌司奴单抗治疗的 CD 患者进行回顾性队列研究。根据先前生物制剂暴露状况对临床、内镜、放射学和生化反应和缓解结果进行分层。使用 Cox 比例风险模型估计生物制剂暴露状况的风险比，并计算愈合的亚组特定发生率。
研究期间共确定 231 例（55.9%为女性，中位年龄 45.8 岁）患者接受乌司奴单抗治疗，其中 2 例患者随后被排除（N=229）。这些患者中，79.0%（181/229）为生物制剂经验丰富者，其中 38.7%（70/181）曾使用过 1 种生物制剂，61.3%（111/181）曾使用过≥2 种生物制剂。在诱导后 3 个月的随访中，生物制剂经验丰富的患者中有 59.1%（62/105）达到临床缓解（Harvey-Bradshaw 指数≤4），生物制剂初治患者中有 79.4%（27/34）达到临床缓解（相对风险[RR]，1.34；95%CI，1.06-1.70；P=0.013）。内镜缓解（无黏膜溃疡）在 37.9%（33/87）的病例中实现。每 1000 人月的内镜愈合率为 72.7（95%CI，42.4-125.1）和 50.2（37.9-66.4）；内镜反应或缓解的中位时间分别为 8.4 个月（95%CI，6.4-9.8）和 15.4 个月（95%CI，10.3-17.9），在生物制剂初治和生物制剂经验丰富的患者中。生物制剂初治患者的影像学反应/缓解和无类固醇缓解率更高。
在这项大型真实世界的 CD 患者队列研究中，患者具有复杂的表型和高比例的先前生物制剂暴露，我们观察到乌司奴单抗在生物制剂初治患者中有效且安全，在一系列终点上提高的比例更高。
