Nguyen Chuong Dinh, Dang Luan Minh, Vo Thong Duy, Bui Hoang Huu, Kim Eun Soo, Mak Joyce Wing Yan, Ooi Choon Jin
Department of Gastroenterology, University Medical Center, Ho Chi Minh City, Vietnam.
Clinical Sciences (International Program), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Therap Adv Gastroenterol. 2025 Sep 11;18:17562848251374638. doi: 10.1177/17562848251374638. eCollection 2025.
Tofacitinib, an oral Janus kinase (JAK) inhibitor, shows promise as a rescue therapy for acute severe ulcerative colitis (ASUC), a life-threatening condition marked by high colectomy rates. This narrative review synthesizes evidence from randomized controlled trials (RCTs), observational studies, and systematic reviews. The efficacy of tofacitinib has been documented, with an 83.01% day-7 response rate in the TACOS trial and 79.9%-86% 90-day colectomy-free survival in steroid-refractory ASUC. However, seven unmet needs impede the adoption of tofacitinib treatment for managing ASUC: (1) a lack of head-to-head RCTs comparing tofacitinib not only to standard rescue therapies like infliximab and ciclosporin but also to other JAK inhibitors like upadacitinib, (2) uncertainty in optimal dosing and duration, (3) ambiguity in positioning tofacitinib in the treatment algorithm, (4) undefined patient selection criteria, notably for those with prior biologic exposure, (5) limited long-term efficacy and cost-utilization data, (6) unresolved safety risks (e.g., infections, thrombosis), and (7) underexplored potential for combination therapy. These gaps undermine the widespread use of tofacitinib in reducing surgical burden and improving outcomes. Collaborative research-especially multi-center RCTs comparing tofacitinib to infliximab, ciclosporin, and next-generation JAK inhibitors-is vital for establishing evidence-based protocols. Addressing these needs could optimize tofacitinib-based ASUC management, offering a rapid, oral alternative to enhance patient care.
托法替布是一种口服的 Janus 激酶（JAK）抑制剂，有望作为急性重症溃疡性结肠炎（ASUC）的挽救疗法，ASUC 是一种以高结肠切除术发生率为特征的危及生命的疾病。本叙述性综述综合了来自随机对照试验（RCT）、观察性研究和系统评价的证据。托法替布的疗效已有记录，在 TACOS 试验中第 7 天的缓解率为 83.01%，在类固醇难治性 ASUC 中 90 天无结肠切除术生存率为 79.9%-86%。然而，有七个未满足的需求阻碍了托法替布用于 ASUC 的治疗：（1）缺乏头对头的 RCT，不仅将托法替布与英夫利昔单抗和环孢素等标准挽救疗法进行比较，还与乌帕替尼等其他 JAK 抑制剂进行比较；（2）最佳剂量和疗程的不确定性；（3）在治疗方案中托法替布定位的模糊性；（4）未明确的患者选择标准，特别是对于那些既往有生物制剂暴露史的患者；（5）长期疗效和成本效益数据有限；（6）未解决的安全风险（如感染、血栓形成）；（7）联合治疗的潜力未得到充分探索。这些差距削弱了托法替布在减轻手术负担和改善结局方面的广泛应用。合作研究——尤其是将托法替布与英夫利昔单抗、环孢素和下一代 JAK 抑制剂进行比较的多中心 RCT——对于建立基于证据的方案至关重要。满足这些需求可以优化基于托法替布的 ASUC 管理，提供一种快速的口服替代方案以加强患者护理。
