JAK inhibitors: current position in treatment strategies for use in inflammatory bowel disease

Abstract

Our expanding knowledge of the pathophysiology of inflammatory bowel disease (IBD) has led to the development of a multitude of new therapies, including parenterally administrated biologic agents and new oral small molecules. Tofacitinib is the first compound of a promising class of new small molecules approved for the treatment of IBD. This pan-Janus kinase (JAK) inhibitor (JAKi) targets the four isoforms of cytokine associated JAKs (JAK1, JAK2, JAK3 and TYK2). Next generations JAKi with marked selectivity for specific JAK isoforms or gut-restricted effect are in development, with promising results in phase I and II clinical trials. Whether increased JAK selectivity will translate into more favorable clinical efficacy and safety profiles remains to be demonstrated in larger clinical trials. Here we provide an overview of the clinical and pharmacological aspects of these drugs and discuss how they may be incorporated in the current treatment paradigm for Crohn's disease and ulcerative colitis.