a Inflammatory Bowel Disease Group , Institut d'Investigacions Biomètiques August Pi I Sunyer (IDIBAPS) , Barcelona , Spain.
b Department of Gastroenterology , Hospital Clínic de Barcelona , Barcelona , Spain.
Expert Rev Clin Immunol. 2018 Nov;14(11):881-892. doi: 10.1080/1744666X.2018.1532291. Epub 2018 Oct 11.
New generations of small molecules are being developed for the treatment of ulcerative colitis. Among them, tofatinib (a Janus kinase (JAK) inhibitor) has demonstrated efficacy for inducing and maintaining remission and achieving mucosal healing with a reasonable safety profile. Oral administration is attractive for patients and lack of immunogenicity represents an advantage over biologic drugs. Areas covered: This review discusses the molecular aspects of the JAK-STAT pathway; the mechanism of action of tofacitinib pertinent to ulcerative colitis and the evidence on the efficacy of tofacitinib for achieving clinically relevant outcomes, including clinical remission, mucosal healing, and normalization of quality of life, as well as safety aspects with special attention to adverse events related to the mode of action of the drug. Expert commentary: Tofacitinib will be the first drug on the class of JAK inhibitors to be available for treatment of ulcerative colitis. The efficacy of the drug, with a rapid onset of action even in cases of severe colitis, oral administration, and possibility to use the drug intermittently without generating immunogenicity, will bring about a redesign of current treatment paradigms for ulcerative colitis.
新一代小分子药物正在被开发用于治疗溃疡性结肠炎。其中,托法替尼(一种 Janus 激酶(JAK)抑制剂)已被证明在诱导和维持缓解以及实现黏膜愈合方面具有疗效,且安全性良好。口服给药对患者具有吸引力,而且与生物药物相比,其缺乏免疫原性是一个优势。
本综述讨论了 JAK-STAT 通路的分子方面;托法替尼在溃疡性结肠炎中的作用机制以及托法替尼在实现临床相关结局方面的疗效证据,包括临床缓解、黏膜愈合和生活质量的正常化,以及特别关注与药物作用模式相关的不良事件的安全性方面。
托法替尼将成为首个用于治疗溃疡性结肠炎的 JAK 抑制剂类药物。该药具有快速的作用机制(甚至在严重结肠炎的情况下)、口服给药、以及无需产生免疫原性即可间歇性使用的可能性,这将彻底改变溃疡性结肠炎的现有治疗模式。