Colon to Rectum
Gut. 2025;74(2):197-205
Top-down infliximab plus azathioprine versus azathioprine alone in patients with acute severe ulcerative colitis responsive to intravenous steroids: A parallel, open-label randomised controlled trial, the ACTIVE trial
Background: It is unknown which maintenance therapy is the most effective option for patients admitted for an acute severe ulcerative colitis (ASUC) episode responding to intravenous steroids.
Methods: The authors conducted a multicentre, parallel-group, open-label randomised controlled trial among 23 French centres in thiopurine and biologics-naïve adults admitted for ASUC responding to intravenous steroids. Eligible patients were randomly assigned to receive infliximab (IFX) and azathioprine (AZA) with a 7-day steroid tapering scheme (IFX + AZA arm) or AZA and conventional standardised steroid tapering regimen (AZA arm). The primary composite endpoint was treatment failure at week 52, defined as the absence of steroid-free clinical remission, the absence of endoscopic response, the use of a prohibited treatment for relapse, severe adverse event leading to treatment interruption, colectomy or death. Multiple imputation for missing data was performed.
Findings: Among the 64 patients randomised (Lichtiger score 13.5 ± 2.0; median age of 34.5 [P25–P75 26.3–50.3] years, median C reactive protein of 29.0 [12.8–96.8] mg/l at baseline): 32 were assigned to the IFX + AZA arm and 32 to the AZA arm. In the intention-to-treat population, treatment failure at week 52 was observed in 22 of 27 (81.5%) in the AZA arm and 16 of 30 (53.3%) in the IFX + AZA arm (risk ratio = 3.85, 95% confidence interval: 1.15–12.88, p = 0.03). 29 adverse events were severe, including 13 disease exacerbations, 6 severe infections without any difference between both arms.
Interpretation: Combination therapy with infliximab and azathioprine was more effective at 1 year than azathioprine alone to avoid treatment failure in patients with acute severe ulcerative colitis responding to intravenous steroids.