Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Aliment Pharmacol Ther. 2020 May;51(9):880-888. doi: 10.1111/apt.15689. Epub 2020 Apr 1.
Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).
To evaluate effectiveness, safety and use of tofacitinib in daily practice.
UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation.
In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively.
Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients.
托法替布是一种已被批准用于治疗溃疡性结肠炎（UC）的 Janus 激酶抑制剂。
评估托法替布在日常实践中的疗效、安全性和使用情况。
在荷兰的 15 家医院，前瞻性招募开始接受托法替布治疗的 UC 患者。在第 12 周和第 24 周，评估无皮质类固醇临床缓解（短临床结肠炎活动指数[SCCAI]≤2）、生化缓解（粪便钙卫蛋白水平≤250μg/g）、无皮质类固醇临床和生化缓解联合、缓解预测因素、安全性结局、治疗剂量以及对血脂的影响。在有常规内镜评估的中心评估内镜结果。
共随访了 123 例 UC 患者（95%抗 TNF、62%vedolizumab 和 3%ustekinumab 经历），中位时间为 24 周（四分位距 12-26 周）。第 24 周时，无皮质类固醇临床、生化和联合无皮质类固醇临床和生化缓解的患者比例分别为 29%（n=22/77）、25%（n=14/57）和 19%（n=11/57）。第 12 周时，21%的患者达到内镜缓解（Mayo=0）（n=7/33）。先前使用 vedolizumab 与临床缓解降低相关（比值比 0.33，95%置信区间[CI]0.11-0.94）。第 24 周时，仍有 33%（n=14/42）的患者使用托法替布 10mg 每日两次。共有 33 例（89 例患者年）托法替布相关不良事件发生，7 例（占总队列的 6%）导致停药。诱导治疗期间，胆固醇、HDL 和 LDL 水平分别升高 18%（95%CI9-26）、18%（95%CI8-28）和 21%（95%CI14-39）。
托法替布是抗 TNF 和 vedolizumab 治疗失败后治疗 UC 的有效药物。然而，观察到较高的不良事件发生率，导致 6%的患者停药。
