Dal Buono Arianna, Gabbiadini Roberto, Solitano Virginia, Vespa Edoardo, Parigi Tommaso Lorenzo, Repici Alessandro, Spinelli Antonino, Armuzzi Alessandro
IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
Clin Exp Gastroenterol. 2022 Jul 23;15:121-128. doi: 10.2147/CEG.S350193. eCollection 2022.
Patients affected by moderate-to-severe Ulcerative Colitis (UC) demand a challenging management. Small molecules, administrated as oral agents, have the ambition of overcoming the limitations of the biologic agents (ie, parenteral administration, rapidity of action, primary and secondary non-responsiveness). Beyond tofacitinib, a pan-Janus kinase (JAK) inhibitor already approved for the treatment of moderate-to-severe UC, novel more selective molecules like filgotinib are being currently evaluated in randomized clinical trials. We aimed to review the current evidence on filgotinib, a JAK-1 preferential inhibitor, in the treatment of UC and its place in therapy in the current scenario.
PubMed and EMBASE were searched to identify relevant studies: those investigating the efficacy and safety of filgotinib in the treatment of UC patients were included in this narrative review.
The current preliminary data have shown that filgotinib is safe and effective in inducing clinical end endoscopic response in both biologic-naïve and biologic-experienced patients with moderate-to-severe UC, also with high inflammatory burden at baseline. In the SELECTION trial, one case of pulmonary embolism occurred with filgotinib 200 mg induction, and three venous thrombosis cases were observed in the placebo maintenance/LTE; the incidence of herpes zoster was ≤1% in all UC treated patients. Filgotinib represents an appealing treatment option for its high selectiveness, route of administration and rapidity of action; cost-effectiveness studies and head-to-head trials are needed to better define its place in therapy.
中重度溃疡性结肠炎（UC）患者的治疗颇具挑战性。作为口服制剂的小分子药物，有望克服生物制剂的局限性（如肠胃外给药、起效速度、原发性和继发性无反应性）。除了已获批用于治疗中重度UC的泛JAK激酶（JAK）抑制剂托法替布外，新型更具选择性的分子如非戈替尼目前正在随机临床试验中进行评估。我们旨在综述关于JAK-1优先抑制剂非戈替尼治疗UC的现有证据及其在当前治疗方案中的地位。
检索PubMed和EMBASE以确定相关研究：本叙述性综述纳入了那些调查非戈替尼治疗UC患者疗效和安全性的研究。
目前的初步数据表明，非戈替尼在诱导初治生物制剂和有生物制剂治疗史的中重度UC患者的临床和内镜反应方面是安全有效的，这些患者在基线时也有较高的炎症负担。在SELECTION试验中，200mg诱导剂量的非戈替尼治疗出现1例肺栓塞，安慰剂维持/LTE期观察到3例静脉血栓形成病例；所有接受治疗的UC患者中带状疱疹的发生率≤1%。非戈替尼因其高选择性、给药途径和起效速度而成为一种有吸引力的治疗选择；需要进行成本效益研究和头对头试验以更好地确定其在治疗中的地位。
