Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis
Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis
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DOI：
10.1016/j.cgh.2018.07.009
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发表时间：
2019-01-01
影响因子：
12.6
通讯作者：
Su, Chinyu
中科院分区：
文献类型：
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作者：
Hanauer, Stephen;Panaccione, Remo;Su, Chinyu
背景与目的：托法替尼是一种口服小分子JAK抑制剂，用于治疗溃疡性结肠炎（UC）。我们通过对2项使用托法替尼诱导治疗UC患者的3期试验（OCTAVE诱导1和2）数据的事后分析，评估了症状改善的开始。方法：研究纳入了中度至重度活动性UC患者，这些患者对皮质类固醇、硫嘌呤和/或肿瘤坏死因子（TNF）拮抗剂不耐受或先前治疗失败。患者接受tofacitinib （10 mg，每日2次，n = 905）或安慰剂（n = 234）治疗8周。使用治疗前15天的日记数据计算每日梅奥大便频率和直肠出血亚评分。我们分析了来自亚组的数据，包括先前抗肿瘤坏死因子治疗失败、基线皮质类固醇使用和基线血清c反应蛋白水平。结果：在第3天，托法替尼与安慰剂组患者在基线大便频率亚评分（托法替尼：-0.27 vs安慰剂：-0.11;P < 0.01）、每日排便次数（-1.06 vs -0.27; P < 0.0001）和直肠出血亚评分（-0.30 vs -0.14; P < 0.01）的降低方面的平均变化显著大于安慰剂组。与安慰剂相比，更多接受托法替尼治疗的患者在第3天大便频率亚评分（托法替尼组降低>= 1分，241/ 837,28.8%,39/ 218,17.9%）和直肠出血亚评分（托法替尼组降低>= 1分，266/ 830,32.0%,43/ 214,20.1%）较基线降低（P < 0.01）。在所有亚组中观察到托法替尼的一致效果。结论：在对UC患者使用托法替尼诱导治疗的3期试验数据的事后分析中，我们发现与安慰剂相比，使用托法替尼的患者在3天内症状有显著改善。这些发现表明该药物对UC患者起效迅速。
BACKGROUND & AIMS: Tofacitinib is an oral, small molecule inhibitor of JAK for the treatment of ulcerative colitis (UC). We evaluated the onset of symptom improvement in post-hoc analyses of data from 2 phase 3 trials of induction therapy with tofacitinib in patients with UC (OCTAVE Induction 1 and 2).METHODS: The studies comprised patients with moderate to severe active UC who were intolerant to, or failed by previous treatment with, corticosteroids, thiopurines, and/or tumor necrosis factor (TNF) antagonists. Patients received tofacitinib (10 mg twice daily, n = 905) or placebo (n = 234) for 8 weeks. Daily Mayo stool frequency and rectal bleeding subscores were calculated using diary data from the first 15 days of therapy. We analyzed data from subgroups including failure of prior anti-TNF therapy, baseline corticosteroid use, and baseline serum levels of C-reactive protein.RESULTS: Mean changes were significantly greater in patients given tofacitinib vs placebo in reductions from baseline stool frequency subscore (tofacitinib: -0.27 vs placebo: -0.11; P < .01), total number of daily bowel movements (-1.06 vs -0.27; P < .0001), and rectal bleeding subscore (-0.30 vs -0.14; P < .01) by day 3. Compared with placebo, more tofacitinib-treated patients had reductions from baseline in stool frequency subscore (by >= 1 point for tofacitinib, 241/837, 28.8% vs placebo, 39/218, 17.9%) (P < .01) and rectal bleeding subscore (by >= 1 point for tofacitinib, 266/830, 32.0% vs placebo, 43/214, 20.1%) (P < .01) by day 3. A consistent effect of tofacitinib was observed in all subgroups.CONCLUSIONS: In a post-hoc analysis of data from phase 3 trials of induction therapy with tofacitinib in patients with UC, we found significant improvements in symptoms among patients given tofacitinib compared with placebo within 3 days. These findings indicate the rapid onset of effect of this drug in patients with UC.