Department of Internal Medicine, Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan; Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan; Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan.
Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan.
Clin Gastroenterol Hepatol. 2021 Oct;19(10):2112-2120.e1. doi: 10.1016/j.cgh.2021.05.038. Epub 2021 May 25.
BACKGROUND & AIMS: Despite rescue therapy, more than 30% of patients with acute severe ulcerative colitis (ASUC) require colectomy. Tofacitinib is a rapidly acting Janus kinase inhibitor with proven efficacy in ulcerative colitis. Tofacitinib may provide additional means for preventing colectomy in patients with ASUC.
A retrospective case-control study was performed evaluating the efficacy of tofacitinib induction in biologic-experienced patients admitted with ASUC requiring intravenous corticosteroids. Tofacitinib patients were matched 1:3 to controls according to gender and date of admission. Using Cox regression adjusted for disease severity, we estimated the 90-day risk of colectomy. Rates of complications and steroid dependence were examined as secondary outcomes.
Forty patients who received tofacitinib were matched 1:3 to controls (n = 113). Tofacitinib was protective against colectomy at 90 days compared with matched controls (hazard ratio [HR], 0.28, 95% confidence interval [CI], 0.10-0.81; P = .018). When stratifying according to treatment dose, 10 mg three times daily (HR, 0.11; 95% CI, 0.02-0.56; P = .008) was protective, whereas 10 mg twice daily was not significantly protective (HR, 0.66; 95% CI, 0.21-2.09; P = .5). Rate of complications and steroid dependence were similar between tofacitinib and controls.
Tofacitinib with concomitant intravenous corticosteroids may be an effective induction strategy in biologic-experienced patients hospitalized with ASUC. Prospective trials are needed to identify the safety, optimal dose, frequency, and duration of tofacitinib for ASUC.
尽管进行了挽救性治疗，但仍有 30%以上的急性重度溃疡性结肠炎（ASUC）患者需要结肠切除术。托法替尼是一种快速起效的 Janus 激酶抑制剂，已被证实对溃疡性结肠炎有效。托法替尼可能为 ASUC 患者预防结肠切除术提供了额外的手段。
我们进行了一项回顾性病例对照研究，评估了生物制剂经验性治疗的 ASUC 患者接受静脉用皮质类固醇治疗后使用托法替尼诱导治疗的疗效。根据性别和入院日期，托法替尼患者与对照组进行 1:3 匹配。使用 Cox 回归校正疾病严重程度，我们估计了 90 天内结肠切除术的风险。作为次要结局，我们还检查了并发症和激素依赖的发生率。
40 例接受托法替尼治疗的患者与对照组（n=113）进行了 1:3 匹配。与对照组相比，托法替尼在 90 天内可降低结肠切除术的风险（风险比[HR]，0.28，95%置信区间[CI]，0.10-0.81；P=0.018）。根据治疗剂量分层，10 mg，每日 3 次（HR，0.11；95%CI，0.02-0.56；P=0.008）具有保护作用，而 10 mg，每日 2 次则没有明显的保护作用（HR，0.66；95%CI，0.21-2.09；P=0.5）。托法替尼组和对照组的并发症发生率和激素依赖性相似。
托法替尼联合静脉用皮质类固醇可能是生物制剂经验性治疗的 ASUC 住院患者的有效诱导策略。需要前瞻性试验来确定托法替尼治疗 ASUC 的安全性、最佳剂量、频率和持续时间。
