Feinberg School of Medicine, Northwestern University, Evanston, Illinois.
Inflammatory Bowel Disease Unit, Department of Medicine, University of Calgary, Calgary, Canada.
Clin Gastroenterol Hepatol. 2019 Jan;17(1):139-147. doi: 10.1016/j.cgh.2018.07.009. Epub 2018 Sep 10.
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).
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.
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.
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. ClinicalTrials.gov no: NCT01465763 and NCT01458951.
托法替尼是一种用于治疗溃疡性结肠炎（UC）的口服小分子 JAK 抑制剂。我们评估了托法替尼诱导治疗 2 项 3 期临床试验数据的事后分析中症状改善的起始时间，这些研究纳入了对皮质类固醇、巯嘌呤和/或肿瘤坏死因子（TNF）拮抗剂不耐受或先前治疗失败的中重度活动期 UC 患者。患者接受托法替尼（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 Mayo 粪便频率和直肠出血亚评分。我们分析了包括先前抗 TNF 治疗失败、基线时使用皮质类固醇和基线时 C 反应蛋白水平在内的亚组数据。
与安慰剂相比，接受托法替尼治疗的患者在粪便频率亚评分（托法替尼：-0.27 vs 安慰剂：-0.11；P <.01）、每日排便次数（托法替尼：-1.06 vs 安慰剂：-0.27；P <.0001）和直肠出血亚评分（托法替尼：-0.30 vs 安慰剂：-0.14；P <.01）方面的改善幅度明显更大。与安慰剂相比，更多的托法替尼治疗患者的粪便频率亚评分（托法替尼：≥1 分，241/837，28.8% vs 安慰剂：39/218，17.9%）（P <.01）和直肠出血亚评分（托法替尼：≥1 分，266/830，32.0% vs 安慰剂：43/214，20.1%）（P <.01）在第 3 天也有改善。托法替尼在所有亚组中均观察到一致的效果。
在托法替尼诱导治疗 UC 的 3 期临床试验数据的事后分析中，我们发现与安慰剂相比，接受托法替尼治疗的患者在 3 天内症状有显著改善。这些发现表明，该药物在 UC 患者中的作用起效迅速。临床试验注册：NCT01465763 和 NCT01458951。
