Azathioprine or 6‐mercaptopurine for induction of remission in Crohn's disease

Background The results from controlled clinical trials investigating the efficacy of azathioprine and 6‐mercaptopurine for the treatment of active Crohn's disease have been conflicting and controversial. An updated meta‐analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease. Objectives The primary objective was to determine the efficacy and safety of azathioprine and 6‐mercaptopurine for induction of remission in active Crohn's disease. Search methods We searched MEDLINE, EMBASE and the Cochrane Library from inception to 30 October 2015. Review articles and conference proceedings were also searched to identify additional studies. Selection criteria Randomized controlled trials (RCTs) of oral azathioprine or 6‐mercaptopurine compared to placebo or active therapy involving adult patients with active Crohn's disease were selected for inclusion. Data collection and analysis Data were extracted by two independent observers based on the intention‐to‐treat principle. Outcomes of interest included: clinical remission, clinical improvement, fistula improvement or healing, steroid sparing, adverse events, withdrawals due to adverse events and serious adverse events. We calculated the pooled relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria. Main results Thirteen RCTs (n = 1211 patients) of azathioprine and 6‐mercaptopurine therapy in adult patients were identified: nine included placebo comparators and six included active comparators. The majority of included studies were rated as low risk of bias. There was possibly a modest difference in clinical remission rates between azathioprine or 6‐mercaptopurine and placebo. Forty‐eight per cent (95/197) of patients receiving antimetabolites achieved remission compared to 37% (68/183) of placebo patients (5 studies, 380 patients; RR 1.23, 95% CI 0.97 to 1.55; moderate quality evidence). There was possibly a modest difference in clinical improvement rates between azathioprine or 6‐mercaptopurine and placebo. Forty‐eight per cent (107/225) of patients receiving antimetabolites achieved clinical improvement or remission compared to 36% (75/209) of placebo patients (8 studies, 434 patients; RR 1.26, 95% CI 0.98 to 1.62; moderate quality eviden