Efficacy and Safety of Janus Kinase-Inhibitors in Ulcerative Colitis

Abstract

Background: Janus kinase-inhibitors (JAK-i) have recently been approved for treating patients with Ulcerative Colitis (UC); therefore, further information is needed, particularly regarding efficacy and safety. Objectives: To provide a comprehensive review regarding the efficacy and safety of currently available JAK-i in UC. Methods: The PubMed and Scopus databases were considered, searching for ‘JAK’, ‘JAK-inhibitor’, ‘Janus Kinases’, ‘Tofacitinib’, ‘Filgotinib’, ‘Upadacitinib’, individually or in combination with ‘IBD’, ‘Ulcerative Colitis’, ‘safety’, ‘efficacy’, ‘study’ and ‘trial’. The search was focused on full-text papers published in English, with no publication date restrictions. Results: The efficacy and safety of JAK-i approved for treating patients with UC have been summarized. These included Tofacitinib, Filgotinib and Upadacitinib. Findings from both clinical trials and real-life studies in UC were reported, with particular regard to their efficacy in inducing clinical response and remission, steroid-free remission and endoscopic and histological healing. Overall, JAK-i proved to be effective and safe in selected subgroups of patients with UC. The rapid onset of action and the oral route of administration represent the most relevant characteristics of these drugs. Safety concerns using Tofacitinib in subgroups of patients (infections, hypercholesterolemia, venous thromboembolism and cardiovascular events) were initially raised. More recently, all JAK-i for UC showed an overall satisfactory safety profile. However, indication should be carefully given. Conclusions: The use of JAK-i UC is promising, although no predictive markers of response are currently available. Optimizing their use, as monotherapy or combined with other immunomodulators, may increase their efficacy in appropriately selected subgroups of patients with UC.