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.
Highlights
As many questions about safety and efficacy of small molecules still remain unclear, in our review we present the current data on approved Janus kinase (JAK) inhibitors, as well as those in clinical development for the treatment of Inflammatory bowel disease (IBD)
Tofacitinib is the first JAKs inhibitor approved by Food and Drug Administration (FDA) in 2018 for the treatment of patients with moderate-to-severe ulcerative colitis (UC) based on two induction and one 52-week maintenance randomized controlled trials (RTCs) [18]
Data from a Phase 2 study of patients with Crohn’s disease (CD) treated with filgotinib, the JAK1-selective inhibitor, showed no differences in serious adverse events (AE) compared with the placebo
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The introduction of antibody-based biologics, mainly tumor necrosis factor-α (TNF-α) inhibitors, has revolutionized the outcomes of IBD therapy, many patients remain unresponsive or lose the response during treatment. Compared to antibody-based biologics, JAK inhibitors are small molecules, with the advantage of being the first targeted IBD therapy administered orally, which is more acceptable than the intravenous or subcutaneous route of administration. In contrast to monoclonal antibodies, which are able to block a single cytokine (TNF-α, IL-12 or IL-23), JAK inhibitors have the potential to affect multiple cytokine-dependent immune pathways, which may improve the therapeutic response of some patients with IBD [12]. As many questions about safety and efficacy of small molecules still remain unclear, in our review we present the current data on approved JAK inhibitors, as well as those in clinical development for the treatment of IBD
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