Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment

Abstract

Although development of biologics has importantly improved the effectiveness in inducing and maintaining remission in inflammatory bowel disease (IBD), biologic therapies still have several limitations. Effective, low-cost drug therapy with good safety profile and compliance is therefore a substantial unmet medical need. A promising target for IBD treatment strategies are Janus kinase (JAK) inhibitors, which are small molecules that interact with cytokines implicated in pathogenesis of IBD. In contrast to monoclonal antibodies, which are able to block a single cytokine, JAK inhibitors have the potential to affect multiple cytokine-dependent immune pathways, which may improve the therapeutic response in some IBD patients. Tofacitinib, inhibiting signaling via different types of JAKs, has been already approved for ulcerative colitis, and several other small-molecule are still under investigation. However, one of the main concerns about using JAK inhibitors is the risk of thromboembolic events. Moreover, patients with COVID-19 appear to have an increased susceptibility for immunothrombosis. Therefore, thrombotic complications may become a serious limitation in the use of JAK inhibitors in the SARS-CoV-2 pandemic. As many questions about safety and efficacy of small molecules still remain unclear, in our review we present the current data regarding approved JAK inhibitors, as well as those in clinical development for the treatment of IBD.