Pancreatitis associated with azathioprine and 6-mercaptopurine use in Crohn’s disease: A systematic review

Abstract

Background Thiopurines are proven agents in the treatment of Crohn’s disease. While pancreatitis is recognised as an adverse event associated with therapy, the effect-size and morbidity of thiopurine-induced pancreatitis is not known. The aim of this systematic review and meta-analysis was to quantify the risk of pancreatitis with azathioprine and 6-mercaptopurine within Crohn’s disease.
Methods We searched six electronic databases from inception to 29th October 2019. The primary outcomes measures were the occurrence of pancreatitis. We calculated pooled odds ratio with corresponding 95% confidence intervals for risk of pancreatitis. A number needed to harm analysis was performed.
Results The search identified 4,418 studies, of which 25 RCTs met the criteria for inclusion. The number of patients treated with azathioprine to cause an episode of pancreatitis was 36 (induction of remission) and 31 (maintenance of remission).The risk of pancreatitis in patients receiving azathioprine across all contexts was 3.80%, compared to a control risk of 0.2% (placebo) and 0.5% (5-ASA agents). There was no difference seen between 6-MP and placebo, although this was a low certainty result due to imprecision from very low event numbers and patient numbers.
Conclusion
There is a probably increased occurrence of pancreatitis when azathioprine is used in Crohn’s disease (moderate certainty), with incidence overall approximately 3.8%. Most cases are mild and resolve on cessation of therapy and no mortality was reported. There was no increased occurrence seen when using 6-MP, although this is a low certainty finding.