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Abstract：
OBJECTIVE: There is an unmet need in the treatment of perianal fistulising 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 randomised [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 randomised. 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].
METHODS: This phase 2, double-blind, multicentre trial enrolled adults with PFCD and prior treatment failure. Participants were randomised [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 randomised. 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].
摘要：
目的：在治疗肛周吻合性克罗恩病[PFCD]方面存在未满足的需求。这项研究评估了Janus激酶1优先抑制剂的疗效和安全性，filgotinib,用于治疗PFCD。
方法：此阶段2，双盲，多中心试验纳入患有PFCD且先前治疗失败的成人。参与者被随机分配[2：2：1]接受菲尔戈替尼200毫克，菲尔戈替尼100毫克，或安慰剂，每天口服一次，持续24周。主要终点是综合瘘管反应（通过物理评估确定的至少一个引流外部开口从基线减少，在第24周，骨盆磁共振成像[MRI]上没有>1cm的液体收集）。
结果：在2017年4月至2020年7月期间，对106名个体进行了筛查，其中57人被随机分组。在菲尔戈替尼200mg组中，停药率最低（3/17[17.6％]对菲尔戈替尼100mg的13/25[52.0％]和安慰剂的9/15[60.0％]）。在菲尔戈替尼200mg组中，在第24周达到联合瘘管反应的参与者比例为47.1％（8/17;90％置信区间[CI]26.0，68.9％），filgotinib100mg组29.2%[7/24;90%CI14.6,47.9%],安慰剂组为25.0%[3/12；90%CI7.2，52.7%]。使用菲尔戈替尼200mg（5/17[29.4%]）比使用安慰剂（1/15[6.7%]）更频繁地发生严重不良事件。没有治疗相关的严重不良事件或死亡。
结论：Filgotinib200mg与安慰剂相比，根据临床和MRI联合发现，肛周瘘引流数量的减少相关。总体耐受性良好[NCT03077412]。
方法：此阶段2，双盲，多中心试验纳入患有PFCD且先前治疗失败的成人。参与者被随机分配[2：2：1]接受菲尔戈替尼200毫克，菲尔戈替尼100毫克，或安慰剂，每天口服一次，持续24周。主要终点是综合瘘管反应（通过物理评估确定的至少一个引流外部开口从基线减少，在第24周，骨盆磁共振成像[MRI]上没有>1cm的液体收集）。
结果：在2017年4月至2020年7月期间，对106名个体进行了筛查，其中57人被随机分组。在菲尔戈替尼200mg组中，停药率最低（3/17[17.6％]对菲尔戈替尼100mg的13/25[52.0％]和安慰剂的9/15[60.0％]）。在菲尔戈替尼200mg组中，在第24周达到联合瘘管反应的参与者比例为47.1％（8/17;90％置信区间[CI]26.0，68.9％），filgotinib100mg组29.2%[7/24;90%CI14.6,47.9%],安慰剂组为25.0%[3/12；90%CI7.2，52.7%]。使用菲尔戈替尼200mg（5/17[29.4%]）比使用安慰剂（1/15[6.7%]）更频繁地发生严重不良事件。没有治疗相关的严重不良事件或死亡。
结论：Filgotinib200mg与安慰剂相比，根据临床和MRI联合发现，肛周瘘引流数量的减少相关。总体耐受性良好[NCT03077412]。
