Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis

Abstract

Background and aim: There are limited evidence based data concerning the use of azathioprine in ulcerative colitis. We aimed to compare the efficacy of azathioprine and oral 5-aminosalicylic acid in inducing remission of steroid dependent ulcerative colitis. Methods: Seventy two patients with steroid dependent ulcerative colitis were admitted to this investigatorblind study. Steroid dependence was defined as a requirement for steroid therapy >10 mg/day during the preceding six months, with at least two attempts to discontinue the medication. The disease had to be clinically and endoscopically active at study entry, and all patients were taking systemic prednisolone (40 mg/day). Patients were randomised to receive azathioprine 2 mg/kg/day or oral 5-aminosalicylic acid 3.2 g/day, for a six month follow up period. The outcome of the treatment was defined as (1) success, indicating induction of clinical and endoscopic remission and steroid discontinuation, or (2) failure, indicating the absence of clinical and endoscopic remission and therefore the need for at least one further cycle of systemic steroids to control symptoms, apart from the initial one, or colectomy. Results: Significantly more patients in the azathioprine than in the 5-aminosalicylic acid group had clinical and endoscopic remission, and discontinued steroid therapy, both in the intention to treat (azathioprine v 5-aminosalicylic acid: 19/36 patients (53%) v 7/36 (21%); odds ratio (OR) 4.78 (95% confidence interval (CI) 1.57-14.5)) and per protocol (azathioprine v 5-aminosalicylic acid: 19/33 patients (58%) v 7/34 (21%); OR 5.26 (95% CI 1.59-18.1)) analysis. Conclusions: Azathioprine is significantly more effective than 5-aminosalicylic acid in inducing clinical and endoscopic remission and avoiding steroid requirement in the treatment of steroid dependent ulcerative colitis.

Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis

“…Ardizzone et al 17 randomized 72 patients with steroid-dependent UC between azathioprine and mesalamine. At 6 months, 53% of patients who received azathioprine were in steroid-free remission vs 21% of those who received mesalamine (odds ratio = 4.78; 95% CI: 1.57-14.5).…”

“…We hypothesized that the effect of parenteral methotrexate in steroid-dependent UC was in the same order of magnitude as rates of remission observed in open trials with methotrexate in UC 16 ; rate of steroid-free remission observed with azathioprine in steroid-dependent UC 17 ; and rate of steroid-free remission observed in CD with parenteral methotrexate. 9 Considering a 2-sided test, a type I error rate of 5%, a statistical power of 80% and an allocation ratio of 1:1, 110 patients were required (PASS 12).…”

Treatment Targets in Inflammatory Bowel Disease: Current Status in Daily Practice

“…However, it remains important to realise that we cannot achieve MH in all IBD patients with the currently available therapies. In UC, varying data on achieving MH with the use of 5-ASA (36,9%-80%) [31,32], azathioprine (53%) [33] and biologics 32%-62% [34][35][36][37] exist, depending on the used definition of MH and duration of follow up. In the case of CD similar results for budesonide (24%) [38], azathioprine (16.5-73%) [38][39][40], combinations of azathioprine and biologics (43,.4%) [39,40], and biologics (20%-63%) [39][40][41][42] exist.…”

Ulcerative proctitis: an update on the pharmacotherapy and management

“…The 1-year relapse rates were significantly lower in patients taking AZA (36%) compared with placebo (59%, p = 0.04) [76]. In a recent randomized clinical trial, steroid-dependent UC patients treated with AZA (2 mg/kg/d) had a significantly higher rate of clinical and endoscopic remission, leading to steroids withdrawal in a greater percentage of cases compared with patients receiving only high-dose oral 5-ASA (53 vs 19%, p = 0.006) [77]. Finally, a randomized study suggests a favourable role of probiotics, which was comparable to mesalamine in the maintenance treatment in UC [78].…”