Background and Aims There is an unmet need for the treatment of perianal fistulizing Crohn’s disease [PFCD]. This study evaluated the efficacy and safety of the Janus kinase 1 preferential inhibitor filgotinib, for the treatment of PFCD. Methods This phase 2, double-blind, multicentre trial enrolled adults with PFCD and prior treatment failure. Participants were randomized [2:2:1] to receive filgotinib 200 mg, filgotinib 100 mg, or placebo once-daily orally for up to 24 weeks. The primary endpoint was combined fistula response [reduction from baseline of at least one draining external opening determined by physical assessment, and no fluid collections >1 cm on pelvic magnetic resonance imaging (MRI)] at week 24. Results Between April 2017 and July 2020, 106 individuals were screened and 57 were randomized. Discontinuations were lowest in the filgotinib 200 mg group [3/17 (17.6%) versus 13/25 (52.0%) for filgotinib 100 mg and 9/15 (60.0%) for placebo]. The proportion of participants who achieved a combined fistula response at week 24 was 47.1% [8/17; 90% confidence interval (CI) 26.0, 68.9%] in the filgotinib 200 mg group, 29.2% [7/24; 90% CI 14.6, 47.9%] in the filgotinib 100 mg group, and 25.0% [3/12; 90% CI 7.2, 52.7%] in the placebo group. Serious adverse events occurred more frequently with filgotinib 200 mg [5/17 (29.4%)] than with placebo [1/15 (6.7%)]. There were no treatment-related serious adverse events or deaths. Conclusions Filgotinib 200 mg was associated with numerical reductions in the number of draining perianal fistulas based on combined clinical and MRI findings compared with placebo, and was generally well tolerated. [NCT03077412]

中文翻译：

---

Filgotinib 治疗肛周瘘管性克罗恩病的功效和安全性 [DIVERGENCE 2]：2 期、随机、安慰剂对照试验

背景和目的 肛周瘘管克罗恩病 [PFCD] 的治疗需求尚未得到满足。本研究评估了 Janus 激酶 1 优先抑制剂 filgotinib 治疗 PFCD 的有效性和安全性。方法 这项 2 期、双盲、多中心试验招募了患有 PFCD 且既往治疗失败的成年人。参与者被随机 [2:2:1] 接受 filgotinib 200 mg、filgotinib 100 mg 或安慰剂，每日口服一次，持续长达 24 周。主要终点是第 24 周时的综合瘘管反应 [通过物理评估确定至少一个引流外部开口较基线减少，盆腔磁共振成像 (MRI) 上没有积液超过 1 cm]。 2017 年 4 月至 7 月的结果2020 年，对 106 人进行了筛查，其中 57 人被随机分配。filgotinib 200 mg 组的停药率最低 [filgotinib 100 mg 组为 3/17 (17.6%)，filgotinib 100 mg 组为 13/25 (52.0%)，安慰剂组为 9/15 (60.0%)]。第 24 周达到联合瘘管反应的参与者比例为 47.1% [8/17; filgotinib 200 mg 组的 90% 置信区间 (CI) 26.0, 68.9%] 29.2% [7/24; filgotinib 100 mg 组的 90% CI 14.6, 47.9%]，以及 25.0% [3/12；安慰剂组的 90% CI 7.2, 52.7%]。filgotinib 200 mg [5/17 (29.4%)] 比安慰剂 [1/15 (6.7%)] 更频繁地发生严重不良事件。没有发生与治疗相关的严重不良事件或死亡。结论 根据临床和 MRI 综合结果，与安慰剂相比，200 mg Filgotinib 与引流肛周瘘管数量减少相关，并且总体耐受性良好。[NCT03077412]