Editorial: Corticosteroid Responsive Acute Severe Ulcerative Colitis—Revisiting Maintenance Approaches in the Era of Advanced Therapies

Abstract

Acute severe ulcerative colitis (ASUC) is a severe form of ulcerative colitis (UC) flare that requires urgent and timely intervention. Approximately one-fourth of patients with UC experience ASUC during their lifetime [1]. ASUC is characterised by frequent bloody bowel movements and systemic inflammatory features. If not adequately controlled, it can lead to toxic megacolon and colonic perforation, often necessitating emergency colectomy. Intravenous corticosteroids remain the first-line treatment, although only about two-thirds of patients respond [2, 3]. For non-responders, medical rescue therapy with cyclosporin, infliximab, or off-label JAK inhibitors (JAKi) may induce response. The primary goal of medical therapy in ASUC is rapid induction of remission, followed by effective maintenance therapy. However, there is limited evidence to guide optimal maintenance therapy following successful induction with corticosteroids.

Singh et al. [4] reported a retrospective propensity-matched analysis comparing the effectiveness and safety of azathioprine and tofacitinib as maintenance therapy in 115 adult patients with ASUC who responded to intravenous corticosteroids. The authors reported a significantly lower cumulative probability of event-free survival (defined as absence of rehospitalization, corticosteroid use, therapy escalation, or colectomy) at 1 year in the azathioprine than in the tofacitinib group (44.0% vs. 75.0%; p = 0.01). Patients managed with azathioprine had higher rates of re-hospitalisation (15.4% vs. 0%; p = 0.003) and treatment escalation (13.8% vs. 2.0%; p = 0.02), and lower rates of symptomatic remission and combined symptomatic plus biomarker remission at 1 year (40.0% vs. 23.1%; p = 0.05; 22.0% vs. 16.9%; p = 0.49, respectively). Although colectomy rates were comparable between the tofacitinib and azathioprine groups, the overall incidence of colectomy remained very low. On multivariate analysis, prior exposure to immunomodulators was associated with reduced maintenance success. A sensitivity analysis excluding patients with prior azathioprine exposure yielded similar results. These findings are consistent with the randomised controlled ACTIVE trial, in which steroid-responsive patients were randomised to receive infliximab and azathioprine or azathioprine alone. The combination therapy group had significantly lower rates of treatment failure over 12 months' follow-up compared to the azathioprine monotherapy group (53.3% vs. 81.5%; p = 0.03) [1].

A single episode of ASUC substantially increases the risk of colectomy, with the risk rising further with subsequent episodes [1]. Even in patients who initially respond to intravenous corticosteroids, the likelihood of relapse and eventual colectomy remains high. While steroid responders may have a lower colectomy risk than those who required medical rescue therapy due to steroid-refractory disease [5], the relapse rate in this group is still considerably high [6]. Notably, although most patients of Singh et al. and all participants in the ACTIVE trial were azathioprine-naïve, a significant proportion on azathioprine monotherapy experienced relapse within 1 year. Although current consensus guidelines recommend thiopurines for maintenance in immunomodulator-naïve patients [7], emerging evidence indicates that azathioprine monotherapy may be less effective than advanced therapies. Therefore, advanced therapies should be considered for long-term maintenance after an ASUC episode, regardless of the initial corticosteroid response.

Mukesh Kumar Ranjan: writing – review and editing, writing – original draft. Sudheer Kumar Vuyyuru: writing – original draft, writing – review and editing.

This article is linked to Singh et al. paper. To view this article, visit https://doi.org/10.1111/apt.70246.