DOP65 Infliximab plus azathioprine and quick steroids discontinuation versus azathioprine plus steroids in patients with acute severe Ulcerative Colitis responding to intravenous steroids: a parallel, open-label randomized controlled trial

Abstract

Abstract Background In patients admitted for acute severe ulcerative colitis (ASUC) responding to intravenous (IV) steroids, the most effective treatment is unknown. In thiopurine-naive patients, thiopurines are appropriate to maintain remission according to current guidelines while the benefit of early infliximab (IFX) therapy remains to be established. Methods In this multicentre, parallel group, open-label randomised controlled trial, thiopurine and biologics-naïve adults admitted for ASUC defined by a Lichtiger score >10 were included between 2016 and 2021 if they responded to IV steroids. They were randomly assigned to receive either combination therapy with IFX and azathioprine (AZA) with a quick steroid discontinuation (IFX+AZA arm), or AZA and standardized steroid tapering regimen (AZA arm). The primary endpoint was treatment failure at W52, defined as absence of steroid-free clinical remission (MCS≤2 with no individual subscore >1), absence of endoscopic response (Endoscopic subscore ≤1), use of a prohibited treatment, adverse event leading to interruption of allocated treatment, colectomy or death. A sample size of 73 patients per group was initially calculated. Due to challenges in recruiting patient, the steering committee decided to prematurely terminate the study blindly of any study results, after including 64 patients. Results 64 were randomised (32 males, age of 34.5 [26.3-50.3] years, Lichtiger score of 13.0 [12-14], CRP of 29.0 [12.8-96.8] mg/L and serum albumin of 31.2 [27.7-35.6] g/L at baseline): 32 were assigned to IFX+AZA arm and 32 to AZA arm. In ITT population, treatment failure at w52 was observed in 81.5% in the AZA arm versus 53.3% in the IFX+AZA arm (OR 3.85 [1.15-12.88], p=0.03). Components of the composite primary endpoint are given in table 1. In PP population, treatment failure at week 52 was observed in 81.5% (22/27) in the AZA arm versus 50.0% (13/26) in the IFX+AZA arm (OR 4.40 [1.28-15.18], p=0.02). In total 121 adverse events (AE) were reported in 40 patients including 23 serious AE in 18 patients (11 in the IFX + AZA arm and 7 in the AZA arm, p=0.24) and 8 leading to treatment interruption (5 in the IFX+AZA arm and 3 in the AZA arm, p=0.39). Serious AE included infectious AE in 6 cases (1 in the AZA arm and 5 in the IFX+AZA arm, p=0.20) and UC relapse in 9 (4 in the AZA arm and 5 in the IFX+AZA arm, p=0.60). No death was reported. Conclusion At w52, combination therapy with IFX + AZA and quick steroids discontinuation was more effective than AZA with standard steroids tapering regimen to prevent treatment failure in patients with ASUC responding to IV steroids. Combination therapy with IFX and AZA should be encouraged in ASUC patients responding to IV steroids (EudraCT 2014-005212-42; study funded by Pfizer).