Abstract and Introduction
Abstract
Background: Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In patients hospitalised for severe flare, who previously experienced multiple drug failures, including steroids and anti-TNF agents, new quick-acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid onset of action.
Aim: To evaluate effectiveness and safety of tofacitinib as rescue therapy in patients hospitalised for UC flare.
Methods: We conducted an observational and multicentre study with both retrospective and prospective collections in 14 GETAID centres. The primary objective was to assess the survival without colectomy following tofacitinib initiation in patients hospitalised for a UC flare. We determined rates of clinical response, clinical remission, and steroid-free clinical remission at week 6 and week 14 and safety.
Results: Fifty-five patients were included (49 with prior infliximab failure and 19 previously exposed to ciclosporin). With a median follow-up of 6.5 months (interquartile range [IQR] [3–12.3]), rate of colectomy-free survival was estimated at 78.9% (95 CI [68.5–90.9]) and 73.6% (95 CI [61.9–87.3]) at 3 and 6 months, respectively. Rates of clinical response, clinical remission and steroid-free clinical remission were 60%, 45.5% and 37.5% at week 6 and 41.8%, 34.5% and 32.7% at week 14. Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zoster infections occurred in patients aged over 60 years old. No venous thrombotic or major adverse cardiovascular events occurred.
Conclusion: Tofacitinib appears as a promising option in patients hospitalised with a UC flare but needs further validation in controlled trials.
Introduction
Fifteen to 25% of patients with ulcerative colitis (UC) have a severe flare that requires an admission to hospital.[1] Standard of care for acute severe ulcerative colitis currently relies on the administration of intravenous steroids. However, up to 40% of patients do not respond to steroids alone and require a second line of treatment. As a second line therapy, infliximab and ciclosporin have a similar efficacy.[2,3] These treatments decrease the rate of colectomy but 20% of patients undergo a colectomy within 3 months.[2] Yet, ciclosporin has a safety profile allowing only a short course of treatment. In addition, many patients have been exposed to an anti-tumour necrosis factor (TNF) agent and are therefore less likely to respond to infliximab. Therefore, additional treatments are needed for patients hospitalised for refractory severe colitis.
Tofacitinib is a rapidly acting, oral, small-molecule Janus kinase inhibitor that is approved for the treatment of UC.[4] It was recently reported in four acute severe colitis patients with a high likelihood of steroids failure that high-intensity tofacitinib could lead to rapid improvement in clinical symptoms and inflammatory biomarkers. One of the four patients did not receive any concomitant steroids along with tofacitinib providing positive perspectives for the use of tofacitinib in severe acute colitis.[5] Subsequently, the effectiveness of tofacitinib in acute severe colitis in two small series gathering a total of 11 anti-TNF-experienced patients has been reported.[6,7] In addition, the rapid onset of action supports the early use of tofacitinib rescue and the quick plasma clearance profile of tofacitinib has the potential advantage of leading patients to surgery cleared from treatment in case of treatment failure.[5]
In the present study, we aimed to determine the effectiveness and the safety of tofacitinib in patients hospitalised for a severe flare of UC. We further evaluated factors associated with colectomy in this setting.
Aliment Pharmacol Ther. 2021;54(3):312-319. © 2021 Blackwell Publishing
