Azathioprine and 6‐mercaptopurine for maintenance of remission in ulcerative colitis

Background Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6‐mercaptopurine for the maintenance of remission is still controversial. Objectives To assess the effectiveness and safety of azathioprine and 6‐mercaptopurine for maintaining remission of ulcerative colitis. Search methods The MEDLINE, EMBASE and Cochrane Library databases were searched from inception to 30 July 2015. Both full randomized controlled trials and associated s were included. Selection criteria Randomized controlled trials of at least 12 months duration that compared azathioprine or 6‐mercaptopurine with placebo or standard maintenance therapy (e.g. mesalazine) were included. Data collection and analysis Two authors independently extracted data using standard forms. Disagreements were solved by consensus including a third author. Study quality was assessed using the Cochrane risk of bias tool. The primary outcome was failure to maintain clinical or endoscopic remission. Secondary outcomes included adverse events and withdrawal due to adverse events. Analyses were performed separately by type of control (placebo, or active comparator). Pooled risk ratios were calculated based on the fixed‐effect model unless heterogeneity was shown. The GRADE approach was used to assess the overall quality of evidence for pooled outcomes. Main results Seven studies including 302 patients with ulcerative colitis were included in the review. The risk of bias was high in three of the studies due to lack of blinding. Azathioprine was shown to be significantly superior to placebo for maintenance of remission. Fourty‐four per cent (51/115) of azathioprine patients failed to maintain remission compared to 65% (76/117) of placebo patients (4 studies, 232 patients; RR 0.68, 95% CI 0.54 to 0.86). A GRADE analysis rated the overall quality of the evidence for this outcome as low due to risk of bias and imprecision (sparse data). Two trials that compared 6‐mercaptopurine to mesalazine, or azathioprine to sulfasalazine showed significant heterogeneity and thus were not pooled. Fifty per cent (7/14) of 6‐mercaptopurine patients failed to maintain remission compared to 100% (8/8) of mesalazine patients (1 study, 22 patients; RR 0.53, 95% CI 0.31 to 0.90). Fifty‐eight per cent (7/12) of azathioprine patients failed to maintain remission compared to 38% (5/13) of sulfasalazine patients (1 study, 25 patients; RR 1.52,