Incidence of liver toxicity in inflammatory bowel disease patients treated with methotrexate: A meta‐analysis of clinical trials

Abstract Background: Crohn's disease and ulcerative colitis are chronic debilitating diseases for which there are multiple treatment options. There are limited data on methotrexate's efficacy and safety profile. Our aim was to estimate the hepatotoxicity associated with its use in inflammatory bowel diseases (IBDs). Methods: We systematically searched the Medline, Cochrane Library, Web of Science, and EMBASE databases and manually examined references in selected articles for trials that used methotrexate as a treatment for IBDs. Thirteen trials that fulfilled the inclusion and exclusion criteria were included in the meta‐analysis. Information on trial and patient characteristics, use of methotrexate as well as other treatments or placebo, and levels of hepatic aminotransferase enzymes were abstracted by two independent investigators using a standardized form. A random effects model was used to pool the incidence rates of reported abnormalities in hepatic aminotransferases. Results: The pooled incidence rate of abnormal hepatic aminotransferase levels (defined as up to a 2‐fold increase over the upper limit of the normal range) in patients treated with methotrexate for IBD was 1.4 per 100 person‐months, while the rate of hepatotoxicity (defined as greater than a 2‐fold over the upper limit of the normal range) was 0.9 per 100 person‐months. The rate of withdrawal from treatment due to these abnormalities was 0.8 per 100 person‐months. Conclusions: The incidence of methotrexate‐related hepatotoxicity as measured by elevation in transaminases and drug withdrawal secondary to elevated transaminases is relatively low. (Inflamm Bowel Dis 2011;)