Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis
Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis
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DOI：
10.1056/nejmoa1606910
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发表时间：
2017-05-04
影响因子：
158.5
通讯作者：
Panes, Julian
中科院分区：
文献类型：
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作者：
Sandborn, William J.;Su, Chinyu;Panes, Julian
研究背景Tofacitinib是一种口服小分子Janus激酶抑制剂，在一项2期试验中显示其作为溃疡性结肠炎的诱导治疗具有潜在疗效。我们进一步评估了托法替尼作为诱导和维持therapy.METHODSWe进行了3期，随机，双盲，安慰剂对照试验的托法替尼治疗成人溃疡性结肠炎的疗效。在OCTAVE诱导1和2试验中，分别有598例和541例既往接受过常规治疗或肿瘤坏死因子拮抗剂治疗的中重度活动性溃疡性结肠炎患者被随机分配接受托法替尼（10 mg，每日两次）或安慰剂诱导治疗8周。主要终点是8周时缓解。在OCTAVE Sustain试验中，593例对诱导治疗有临床应答的患者被随机分配接受托法替尼（5 mg或10 mg，每日两次）或安慰剂维持治疗52周。主要终点是52周时的缓解。在OCTAVE诱导1期试验中，托法替尼组8周时的缓解率为18.5%，安慰剂组为8.2%（P = 0.007）;在OCTAVE诱导2期试验中，托法替尼组8周时的缓解率为16.6%，安慰剂组为3.6%（P
BACKGROUNDTofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy.METHODSWe conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks.RESULTSIn the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P = 0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P