Varyani Fumi, Argyriou Konstantinos, Phillips Frank, Tsakiridou Eirini, Moran Gordon William
Queen's Medical Center, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.
Drug Des Devel Ther. 2019 Dec 2;13:4091-4105. doi: 10.2147/DDDT.S182891. eCollection 2019.
Recent advances in the understanding of the pathophysiology of ulcerative colitis (UC) have led to the expansion of our therapeutic arsenal. Conventional treatment options, including aminosalicylates, corticosteroids, thiopurines, and calcineurin inhibitors, fail to control the disease in a significant proportion of patients. Approximately 25-50% of the patients treated with tumor necrosis factor antibodies (anti-TNFα) are primary and secondary non-responders to therapy. Tofacitinib is a novel orally administered small synthetic molecule that inhibits a homologous family of enzymes, termed Janus kinases that modulate multiple key cytokines involved in the pathogenesis of UC. Phase II and III trials showed promising results in UC, leading the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to approve its administration for the induction and maintenance of remission in moderate-to-severe UC. Herein, we review tofacitinib for the management of UC, its mechanism of action pharmacokinetic properties, efficacy, and safety.
近年来,对溃疡性结肠炎(UC)病理生理学认识的进展促使我们的治疗手段得以扩充。传统治疗方案,包括氨基水杨酸类药物、皮质类固醇、硫唑嘌呤和钙调神经磷酸酶抑制剂,在相当一部分患者中无法有效控制病情。接受肿瘤坏死因子抗体(抗TNFα)治疗的患者中,约25%-50%对治疗原发性和继发性无反应。托法替布是一种新型口服小分子合成药物,可抑制一类名为Janus激酶的同源酶家族,这些酶可调节UC发病机制中多种关键细胞因子。II期和III期试验在UC治疗中显示出了有前景的结果,促使美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)批准其用于中重度UC诱导缓解和维持缓解治疗。在此,我们综述托法替布在UC治疗中的应用、作用机制、药代动力学特性、疗效及安全性。