Janus kinase inhibitors in the management of acute severe ulcerative colitis: a comprehensive review

BACKGROUND: One-third of patients with acute severe ulcerative colitis (ASUC) are steroid-refractory. Cyclosporine and infliximab are currently the mainstays of salvage therapy. Janus kinase inhibitors (JAKi) could play a role in the treatment of ASUC. AIM: To review the evidence on JAKi in the management of ASUC. METHODS: We performed a bibliographic search to identify studies focusing on the treatment of ASUC with JAKi. RESULTS: Potential advantages of JAKi for the management of ASUC include their oral administration, rapid onset of action, short half-life, lack of immunogenicity, and effectiveness in patients with prior biologic exposure. Thirty studies (including 373 patients) have evaluated the efficacy of tofacitinib in ASUC, with a response rate (avoidance of colectomy) ranging between 43% and 100%, with a weighted mean of 82%. Experience with upadacitinib is more limited (only 10 studies and 74 patients are available) but also encouraging: mean colectomy-free rate ranging between 67% and 100%, with a weighted mean of 79%. However, experience with filgotinib in ASUC is currently nonexistent. Regarding safety, the available data does not reveal any new safety concerns when JAKi are used in ASUC, although follow-up periods are still short. CONCLUSION: JAKi seems to be a promising treatment option for ASUC, with both tofacitinib and upadacitinib achieving colectomy-free rates of approximately 80%. Further studies are essential to define whether JAKi can replace cyclosporine/infliximab as second-line therapy for the medical management of ASUC, or whether they can even be used as initial treatment in place of intravenous corticosteroids.