Gisbert Javier P, Chaparro María
Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
J Crohns Colitis. 2025 Feb 4;19(2). doi: 10.1093/ecco-jcc/jjaf021.
One-third of patients with acute severe ulcerative colitis (ASUC) are steroid-refractory. Cyclosporine and infliximab are currently the mainstays of salvage therapy. Janus kinase inhibitors (JAKi) could play a role in the treatment of ASUC.
To review the evidence on JAKi in the management of ASUC.
We performed a bibliographic search to identify studies focusing on the treatment of ASUC with JAKi.
Potential advantages of JAKi for the management of ASUC include their oral administration, rapid onset of action, short half-life, lack of immunogenicity, and effectiveness in patients with prior biologic exposure. Thirty studies (including 373 patients) have evaluated the efficacy of tofacitinib in ASUC, with a response rate (avoidance of colectomy) ranging between 43% and 100%, with a weighted mean of 82%. Experience with upadacitinib is more limited (only 10 studies and 74 patients are available) but also encouraging: mean colectomy-free rate ranging between 67% and 100%, with a weighted mean of 79%. However, experience with filgotinib in ASUC is currently nonexistent. Regarding safety, the available data does not reveal any new safety concerns when JAKi are used in ASUC, although follow-up periods are still short.
JAKi seems to be a promising treatment option for ASUC, with both tofacitinib and upadacitinib achieving colectomy-free rates of approximately 80%. Further studies are essential to define whether JAKi can replace cyclosporine/infliximab as second-line therapy for the medical management of ASUC, or whether they can even be used as initial treatment in place of intravenous corticosteroids.
三分之一的急性重症溃疡性结肠炎（ASUC）患者对类固醇治疗无效。环孢素和英夫利昔单抗是目前挽救治疗的主要手段。Janus激酶抑制剂（JAKi）可能在ASUC的治疗中发挥作用。
综述JAKi在ASUC治疗中的证据。
我们进行了文献检索，以确定聚焦于用JAKi治疗ASUC的研究。
JAKi用于ASUC治疗的潜在优势包括口服给药、起效迅速、半衰期短、无免疫原性以及对先前接受过生物制剂治疗的患者有效。30项研究（包括373例患者）评估了托法替布在ASUC中的疗效，缓解率（避免结肠切除术）在43%至100%之间，加权平均值为82%。乌帕替尼的经验更为有限（仅有10项研究和74例患者），但也令人鼓舞：无结肠切除率在67%至100%之间，加权平均值为79%。然而，目前尚无filgotinib用于ASUC治疗的经验。关于安全性，尽管随访期仍然较短，但现有数据并未显示在ASUC中使用JAKi时存在任何新的安全问题。
JAKi似乎是ASUC一种有前景的治疗选择，托法替布和乌帕替尼的无结肠切除率均达到约80%。进一步的研究对于确定JAKi是否能够取代环孢素/英夫利昔单抗作为ASUC药物治疗的二线疗法，或者它们是否甚至可以替代静脉注射皮质类固醇作为初始治疗至关重要。
