A review on Janus Kinase (JAK) inhibitors in ulcerative colitis: A new frontier in GI pharmacotherapy

Ulcerative colitis (UC) is a chronic inflammatory bowel disease significantly impairing patient quality of life and usually requiring a long-term immunosuppressive regime. As far as treatment is concerned, the classical methodsaminosalicylates, corticosteroids, and biologics-have indeed helped to achieve better control; however, a number of patients are not responding adequately or are losing their response during the course of their treatment. JAK inhibitors have emerged as a very interesting class of oral small molecules which target the intracellular JAK-STAT signaling pathway that plays a central role in the pathogenesis of UC. Tofacitinib, as the first JAK inhibitor licensed for the treatment of moderate to severe UC, has been shown in clinical trials to exhibit a swift onset of action with maintenance of remission over the long term. With JAK1-selective agents such as upadacitinib and filgotinib currently being developed further into the therapeutic arena, some safety concerns about infections, thromboembolic events, and long-term safety emerge. This review covers the mechanism behind, clinical efficacy, and safety profile of JAK inhibitors and their place in the management of UC, portraying them as the newest frontier in personalized gastrointestinal pharmacotherapy. Keywords: Ulcerative colitis, Janus kinase inhibitors, JAK-STAT pathway, Tofacitinib, Upadacitinib, Filgotinib, Inflammatory bowel disease, Targeted therapy, Immunomodulators, Gastrointestinal pharmacotherapy