Despite rescue therapy, acute severe ulcerative colitis (ASUC) is associated with a high risk of colectomy, while treatment options remain limited. Tofacitinib, a rapidly acting Janus Kinase (JAK) inhibitor, is gaining ground as an effective alternative treatment option for the management of acute severe ulcerative colitis, which may prevent emergency colectomy.
A systematic literature search of PubMed and Embase was undertaken for studies of adult patients with ASUC treated with tofacitinib.
In total, two observational studies, seven case series and five case reports incorporating 134 patients who received tofacitinib in ASUC were identified with a follow-up period ranging from 30 days to 14 months. Overall, the pooled colectomy rate was 23.9% (95% CI 16.6–31.2). The pooled 90-day and 6-month colectomy free rate were 79.9% (95% CI 73.1–86.7) and 71.6% (95% CI 64–79.2) respectively. The most frequent adverse event was C. Difficile infection.
Tofacitinib may be appropriate as both a first-line and secondline treatment in patients with steroid-resistance ASUC, given the increasing number of patients with primary or secondary failure to anti-TNF. It is estimated that about one third of IBD patients do not respond to anti-TNF therapy , while a loss of response is reported annually in approximately 20% of patients receiving antiTNF therapy. One advantage of tofacitinib as an option for ASUC is that it is a small molecule, and as a result is less affected by hypoalbuminemia and colonic protein loss compared to infliximab . In addition, infliximab has a long half-life, approximately 14 days, and more time may be needed to evaluate the effectiveness compared to tofacitinib. Furthermore, sequential therapy, following non-response to infliximab or cyclosporine remain debated and the existing evidence cannot support a decision for or against the use of sequential rescue therapy due to high risk of severe infections. Tofacitinib may also be considered as first-line rescue therapy since in case of failure, its short half-life and rapid clearance may permit a second line rescue therapy with infliximab or cyclosporine with complete washout from the system within 1–2 days of stopping therapy. This could theoretically lower the risk of cumulative immunosuppression and help mitigate the increased infection risk that has been observed in case series of sequential therapy with infliximab and cyclosporine.
Tofacitinib appears to be a promising option for the treatment of ASUC. Randomized clinical trials are required to further access the efficacy, safety and optimal dose of tofacitinib in cases of ASUC.