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A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta‐analysis
Author(s) -
Kennedy N. A.,
Rhatigan E.,
Arnott I. D. R.,
Noble C. L.,
Shand A. G.,
Satsangi J.,
Lees C. W.
Publication year - 2013
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12511
Subject(s) - azathioprine , mercaptopurine , medicine , thiopurine methyltransferase , ulcerative colitis , inflammatory bowel disease , adverse effect , gastroenterology , disease
Summary Background Thiopurines maintain remission and modify disease course in inflammatory bowel disease. Use is limited by intolerance and subsequent drug withdrawal in approximately 17% of patients treated with azathioprine. Previous case series have addressed the success rates of re‐treatment with mercaptopurine in these individuals. Aims To determine the rate of tolerance when trialling mercaptopurine in azathioprine‐intolerant patients and the factors predictive of success, and to perform a systematic review and meta‐analysis of these data with other published data sets. Methods A retrospective observational study of 149 patients with IBD (82 with Crohn's disease and 67 with ulcerative colitis) previously intolerant of azathioprine subsequently treated with mercaptopurine was performed. A meta‐analysis was undertaken of all published studies of mercaptopurine use in azathioprine‐intolerant patients (455 patients in 11 included studies). Results Mercaptopurine was tolerated by 58% of azathioprine‐intolerant patients in the Edinburgh cohort. In the meta‐analysis, 68% tolerated mercaptopurine. A higher proportion of those in the meta‐analysis with GI toxicity (62%) or hepatotoxicity (81%) were able to tolerate mercaptopurine than those with flu‐like illness (36%). Among those patients who ceased mercaptopurine for further adverse effects, 59% experienced the same adverse effect as they had with azathioprine. Conclusions This meta‐analysis shows that switching to mercaptopurine is a safe therapeutic strategy for over two‐thirds of azathioprine‐intolerant patients and may help optimise immunomodulatory therapy in inflammatory bowel disease. A trial of mercaptopurine should be attempted in IBD patients (except those with acute pancreatitis or bone marrow aplasia) before considering thiopurine intolerance.