Editorial: is tofacitinib another rescue option for acute severe ulcerative colitis?

Abstract

Acute severe ulcerative colitis (ASUC) is associated with a high risk of colectomy with 20% requiring surgery during the first admission, increasing to 40% at the second admission.1 Medical options for rescue therapy after corticosteroid failure are limited to infliximab and ciclosporin. However, there has been recent interest in the use of tofacitinib, an orally administered Janus kinase (JAK) inhibitor, as a rescue agent for ASUC due to its potency and rapid onset of action.2,3 In a recent issue of Alimentary Pharmacology & Therapeutics, Uzzan et al present a multicentre cohort study of tofacitinib use in a biologicrefractory, hospitalised cohort with severe UC.4 This GETAID study comprised a mix of retrospective and prospective data from 55 patients across 14 centres; the primary outcome was survival without colectomy. At 3 months, the rate of colectomyfree survival was 78.9% (95% CI, 68.590.9), remaining almost unchanged at 6 months. Postinduction clinical response, clinical remission and steroidfree clinical remission rates at week 14 were 41.8%, 34.5% and 32.7% respectively. There were no factors predictive of colectomy, and no new safety signals were identified. This is the largest study examining tofacitinib s safety and effectiveness in this setting; hitherto, data were limited to small case series only.58 It is important to recognise the study limitations. This is a realworld, largely retrospective study, with limited followup. As such, collected data are of variable quality and completeness. For example, postinduction endoscopy was seldom performed so mucosal response data are unavailable, and the completeness of biomarker data such as CRP is limited. Equally importantly, the context in which tofacitinib was used needs careful consideration; 53% received intravenous corticosteroids prior to tofacitinib, and only 14.5% and 3.6% received ciclosporin and infliximab, respectively, during the admission. Furthermore, this was a mixed group in terms of disease severity, rather than a pure, ASUC cohort; the mean CRP on admission was 17.2mg/L, and approximately one third of patients had a Mayo endoscopic score of 2. Nevertheless, the results suggest that a proportion of this difficult to treat group of patients respond to tofacitinib. Such benefit needs weighing up with risk which in turn is driven in part by dose. At week 14, 23% of patients had undergone dose reduction of tofacitinib to 5 mg bd based on the treating physician s opinion. As is evident from the registration trials and realworld data, the higher maintenance dose is superior to the lower dose in patients with refractory disease but is also associated with greater risk of adverse events. Longer term followup will help to clarify the riskbenefit balance in patients more likely to require longterm treatment with 10 mg bd. The prospect of another rescue option for ASUC is highly attractive; antiTNF failure is common and longterm ciclosporin use is limited by its side effect profile. This cohort represents a valuable addition to the literature and the authors should be congratulated for assembling the data. Further highquality, controlled studies are warranted to evaluate the efficacy, safety and optimal dosing strategies of JAK inhibition in this setting.