Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials.
Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials.
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DOI：
10.1136/gutjnl-2016-312735
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发表时间：
2017-06
期刊：
影响因子：
24.5
通讯作者：
Maller E
中科院分区：
文献类型：
--
作者：
Panés J;Sandborn WJ;Schreiber S;Sands BE;Vermeire S;D'Haens G;Panaccione R;Higgins PDR;Colombel JF;Feagan BG;Chan G;Moscariello M;Wang W;Niezychowski W;Marren A;Healey P;Maller E
托法替尼是一种口服小分子 Janus 激酶抑制剂，目前正在研究其治疗 IBD 的效果。我们评估了托法替布用于中重度克罗恩病（CD）患者诱导和维持治疗的有效性和安全性。我们进行了两项随机、双盲、安慰剂对照、多中心 IIb 期研究。患有中重度 CD 的成年患者被随机接受安慰剂诱导治疗，即托法替布 5 或 10 mg，每天两次，持续 8 周。那些达到临床反应 100 或缓解的患者被重新随机分配到安慰剂维持治疗组，即托法替布 5 或 10mg，每天两次，持续 26 周。主要终点是诱导研究结束时的临床缓解，以及维持研究结束时的临床缓解100或缓解。诱导研究中随机分配的 180/280 名患者被纳入维持研究。在诱导第 8 周，每天两次 5 毫克和 10 mg 治疗组中，临床缓解的患者比例分别为 43.5% 和 43.0%，而安慰剂组为 36.7%（每天两次 5 毫克和 10 mg 治疗组与安慰剂组相比，p=0.325 和 0.392）。在维持治疗第 26 周，托法替布 10mg 每日两次的临床缓解或缓解患者比例为 55.8%，而托法替布 5mg 每日两次的比例为 39.5%，安慰剂为 38.1%（10mg 每日两次与安慰剂相比，p=0.130）。与安慰剂相比，在诱导治疗和维持治疗后，每日两次 10 mg 的 C 反应蛋白相对于基线的变化具有统计学显着性 (p<0.0001)。尽管有证据表明治疗效果较小，但主要疗效终点与安慰剂没有显着差异。托法替尼没有观察到新的安全信号。 NCT01393626 和 NCT01393899。
Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p<0.0001) with 10 mg twice daily after both induction and maintenance treatments. Primary efficacy endpoints were not significantly different from placebo, although there was evidence of a minor treatment effect. No new safety signals were observed for tofacitinib. NCT01393626 and NCT01393899.
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