BACKGROUND We aimed to evaluate the real-world effectiveness and safety of ustekinumab for the treatment of both bio-naïve and bio-exposed ulcerative colitis (UC) patients in a real-world setting. METHODS Retrospective, Canadian multicenter cohort study. Primary outcomes were clinical remission and endoscopic remission. Key secondary outcomes included composite clinical and endoscopic response, safety, and persistence. Univariable logistic regression was conducted to examine associations between baseline factors and 12 month clinical and endoscopic response and remission. The primary focus was on the association between these outcomes and bio-exposure status. RESULTS A total of 198 patients were included, of whom 47.5% were female and 85.9% under 65 years. The majority had severe endoscopic activity at baseline (47.5%, n=87) and were bio-exposed (88.8%, n=176; 33%, n=66 prior failure of 3 or more biologics). Patients were followed for a median of 12.8 (IQR 8.2 to 22.1) months after induction. The overall clinical remission rates were 41.3% (69/167), 38.1% (56/147), and 43.6% (58/133) at 3, 6 and 12 months, respectively. Endoscopic remission rates (MES=0) were 8.0% (7/88), 18.7% (23/123), and 12.5% (11/88) at 3, 6, and 12 months, respectively, and consistently higher in bio-naïve patients compared to bio-exposed patients through 12 months (p<0.05 at all time points). Bio-naive patients were more likely to achieve endoscopic remission compared to bio-exposed (HR=5.40, 95% CI: 1.08-26.93). Adverse events were reported in 14.1% (18/198). DISCUSSION In a highly refractory and largely bio-exposed population, a substantial proportion of patients with UC treated with ustekinumab can achieve clinical and endoscopic outcomes of importance after 12 months. Prior biologic exposure is associated with lower rates of endoscopic remission.

中文翻译：

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乌司奴单抗对中度至重度溃疡性结肠炎患者的疗效：一项多中心真实世界加拿大研究。


背景 我们旨在评估乌司奴单抗在真实环境中治疗生物初治和生物暴露溃疡性结肠炎 （UC） 患者的真实世界有效性和安全性。方法 回顾性、加拿大多中心队列研究。主要结局是临床缓解和内窥镜缓解。关键的次要结局包括复合临床和内窥镜反应、安全性和持久性。进行单变量 logistic 回归以检查基线因素与 12 个月临床和内窥镜反应和缓解之间的关联。主要关注点是这些结局与生物暴露状况之间的关联。结果 共纳入 198 例患者，其中女性 47.5%，65 岁以下 85.9%。大多数患者在基线时具有严重的内窥镜活动 （47.5%，n=87） 并且有生物暴露 （88.8%，n=176;33%，n=66 既往 3 种或更多生物制剂失败）。患者在诱导后随访中位时间为 12.8 （IQR 8.2 至 22.1）。3 、 6 和 12 个月时总体临床缓解率分别为 41.3% （69/167） 、 38.1% （56/147） 和 43.6% （58/133）。3 、 6 和 12 个月的内窥镜缓解率 （MES=0） 分别为 8.0% （7/88） 、 18.7% （23/123） 和 12.5% （11/88），并且在 12 个月内与生物暴露患者相比，生物初治患者的缓解率 （MES=0） 始终较高 （p<0.05在所有时间点）。与生物暴露患者相比，生物初治患者更有可能实现内窥镜缓解 （HR=5.40,95% CI： 1.08-26.93）。不良事件报告率为 14.1% （18/198）。讨论 在高度难治性和大部分生物暴露的人群中，很大一部分接受乌司奴单抗治疗的 UC 患者可以在 12 个月后获得重要的临床和内窥镜结局。 既往生物暴露与内镜下缓解率较低相关。