Background Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Objective To assess colectomy incidence rates (IRs) and baseline characteristics for the presence of identified colectomy risk factors among patients in the tofacitinib OCTAVE UC clinical program. Design This post hoc analysis evaluated patients in the 8-week OCTAVE Induction 1 and 2, 52-week OCTAVE Sustain, and OCTAVE Open (open-label, long-term extension) studies. Methods IRs [95% confidence interval (CI)] for colectomy were analyzed. Baseline risk factors based on clinical guidelines: aged <40 years at diagnosis, extensive colitis, severe endoscopic disease [Mayo endoscopic subscore (MES) = 3], hospitalization for UC within 12 months, C-reactive protein (CRP) >3 mg/L, and serum albumin <3.5 g/dL. Baseline risk factors were evaluated in patients who underwent colectomy by study and summarized descriptively. Results Over a maximum of 7.8 years of tofacitinib exposure, 14 patients underwent colectomy: 3/1139 (0.3%) in OCTAVE Induction 1 and 2 [tofacitinib 10 mg twice daily (BID): n = 2; placebo: n = 1], 3/593 (0.5%) in OCTAVE Sustain (placebo: n = 3), and 8/944 (0.8%) in OCTAVE Open (tofacitinib 10 mg BID: n = 8). Colectomy IR per 100 patient-years for all patients who received ⩾1 tofacitinib dose was 0.34 (95% CI: 0.16-0.63). All patients who underwent colectomy had ⩾1 risk factor and prior tumor necrosis factor inhibitor (TNFi) failure, among which the most common risk factors were a MES of 3 (n = 13), CRP >3 mg/L (n = 11), and aged <40 years at diagnosis (n = 9). Conclusions Among patients with moderate to severe UC receiving tofacitinib, colectomies were infrequent; all patients undergoing colectomy had prior TNFi failure, and most had multiple additional risk factors. This provides important information to discuss with patients and inform management decisions. Registration NCT01465763; NCT01458951; NCT01458574; and NCT01470612.

中文翻译：

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溃疡性结肠炎患者中存在与结肠切除术相关的危险因素：托法替布 OCTAVE 溃疡性结肠炎临床项目数据的事后分析。

背景托法替布是一种口服小分子 Janus 激酶抑制剂，用于治疗溃疡性结肠炎 (UC)。目的 评估托法替尼 OCTAVE UC 临床项目患者中结肠切除术发生率 (IR) 和是否存在已确定的结肠切除术危险因素的基线特征。设计 这项事后分析评估了 8 周 OCTAVE 诱导 1 和 2、52 周 OCTAVE 维持和 OCTAVE Open（开放标签、长期扩展）研究中的患者。方法 分析结肠切除术的 IR [95% 置信区间 (CI)]。基于临床指南的基线危险因素：诊断时年龄 <40 岁、广泛性结肠炎、严重内镜疾病 [Mayo 内镜评分 (MES) = 3]、12 个月内因 UC 住院、C 反应蛋白 (CRP) >3 mg/ L，血清白蛋白<3.5 g/dL。通过研究评估接受结肠切除术的患者的基线危险因素并进行描述性总结。结果 在托法替布暴露最长 7.8 年的时间里，14 名患者接受了结肠切除术：OCTAVE 诱导 1 和 2 中的 3/1139 (0.3%) [托法替布 10 mg 每天两次 (BID)：n = 2；安慰剂：n = 1]，OCTAVE Sustain 中为 3/593 (0.5%)（安慰剂：n = 3），OCTAVE Open 中为 8/944 (0.8%)（托法替尼 10 mg BID：n = 8）。对于所有接受 1 剂量托法替布的患者，每 100 患者年的结肠切除术 IR 为 0.34（95% CI：0.16-0.63）。所有接受结肠切除术的患者均存在 1 个危险因素且既往肿瘤坏死因子抑制剂 (TNFi) 失败，其中最常见的危险因素是 MES 为 3 (n = 13)、CRP > 3 mg/L (n = 11) ，诊断时年龄 <40 岁 (n = 9)。结论 在接受托法替布治疗的中重度 UC 患者中，结肠切除术很少见；所有接受结肠切除术的患者均曾出现过 TNFi 失败，并且大多数患者还有多种其他危险因素。这提供了与患者讨论并为管理决策提供信息的重要信息。注册号NCT01465763；NCT01458951；NCT01458574；和NCT01470612。