Department of Gastroenterology, Herlev Hospital, Herlev, Denmark.
J Crohns Colitis. 2023 Aug 21;17(8):1354-1363. doi: 10.1093/ecco-jcc/jjad036.
Tofacitinib has emerged as a new potential treatment for acute severe ulcerative colitis [ASUC]. We conducted a systematic review to assess efficacy, safety and integration in ASUC algorithms.
Systematic searching was done in MEDLINE, EMBASE, Cochrane Library and Clinicaltrials.gov until August 17, 2022, including all studies reporting original observations on tofacitinib for ASUC, preferably defined according to Truelove and Witts criteria. The primary outcome was colectomy-free survival.
Of 1072 publications identified, 21 studies were included of which three were ongoing clinical trials. The remaining comprised a pooled cohort originating from 15 case publications [n = 42], a GETAID cohort study [n = 55], a case-control study [n = 40 cases] and a paediatric cohort [n = 11]. Of these 148 reported cases, tofacitinib was used as second-line treatment after steroid failure in previous infliximab failures or third-line after sequential steroid and infliximab or cyclosporine failure, 69 [47%] were female, median age range was 17-34 years and disease duration was 0.7-10 years. Overall, 30-day colectomy-free survival was 85% [n = 123 of 145; n = 3 without colectomy had follow-up <30 days], 90-day 86% [n = 113 of 132; n = 16 follow-up <90 days] and 180-day 69% [n = 77 of 112; n = 36 follow-up <180 days]. Tofacitinib persistence at follow-up was 68-91%, clinical remission 35-69% and endoscopic remission 55%. Adverse events occurred in 22 patients, predominantly being infectious complications other than herpes zoster [n = 13], and resulted in tofacitinib discontinuation in seven patients.
Tofacitinib appears promising for treatment of ASUC with high short-term colectomy-free survival among refractory patients who are otherwise deemed to require colectomy. However, large high-quality studies are needed.
托法替尼已成为急性重度溃疡性结肠炎（ASUC）的一种新的潜在治疗方法。我们进行了一项系统评价，以评估其在 ASUC 中的疗效、安全性和整合情况。
系统检索 MEDLINE、EMBASE、Cochrane 图书馆和 Clinicaltrials.gov 截至 2022 年 8 月 17 日的所有研究，这些研究均报告了托法替尼治疗 ASUC 的原始观察结果，最好根据特鲁尔夫和威茨标准进行定义。主要结局是免于结肠切除术的生存。
在确定的 1072 篇文献中，纳入了 21 项研究，其中 3 项为正在进行的临床试验。其余的研究包括一项来自 15 篇病例报告的汇总队列研究[42 例]、一项 GETAID 队列研究[55 例]、一项病例对照研究[40 例]和一项儿科队列研究[11 例]。在这 148 例报告的病例中，托法替尼是在先前英夫利昔单抗失败后类固醇失败后的二线治疗，或在类固醇和英夫利昔单抗或环孢素序贯失败后的三线治疗，69 例（47%）为女性，中位年龄范围为 17-34 岁，疾病持续时间为 0.7-10 年。总体而言，30 天免于结肠切除术的生存率为 85%（145 例中有 123 例；3 例无结肠切除术的患者随访时间<30 天），90 天为 86%（132 例中有 113 例；16 例随访时间<90 天），180 天为 69%（112 例中有 77 例；36 例随访时间<180 天）。随访时托法替尼的持续率为 68-91%，临床缓解率为 35-69%，内镜缓解率为 55%。22 例患者发生了不良反应，主要是除带状疱疹以外的感染性并发症（13 例），7 例患者因不良反应停止使用托法替尼。
托法替尼治疗 ASUC 有希望，在需要结肠切除术的难治性患者中，具有较高的短期免于结肠切除术的生存率。然而，需要开展大型高质量的研究。
