Letter: successful mercaptopurine therapy after azathioprine‐related pancreatitis in patients with IBD

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The development of azathioprine-related pancreatitis has previously been considered a strict contraindication to subsequent treatment with mercaptopurine; however, there are few data to support this position. Several small studies have reported that mercaptopurine is tolerated in some patients after azathioprine-related pancreatitis. We report a retrospective clinical audit using a prospectively acquired database of patients with IBD treated with azathioprine therapy between 1999 and 2009. Pancreatitis was diagnosed in the presence of abdominal pain and a raised lipase. Pancreatitis was attributed to azathioprine where there was no other cause identified. All patients who developed pancreatitis were treated conservatively with rest, fluids and withdrawal of drug. After a short period of drug washout, mercaptopurine was introduced at a dose of 0.5 mg/kg and increase to 1– 1.5 mg/kg if tolerated after 1–2 months. Statistical analysis was performed using chi-square and student t-tests. A total of 64 patients with inflammatory bowel disease (50% female patients, mean age 41 years, range: 16– 92 years) commenced azathioprine for Crohn’s disease (78%), ulcerative colitis (19%) or indeterminate colitis. A total of 23 patients were intolerant of azathioprine, including seven patients who developed pancreatitis. Pancreatitis occurred within a mean of 24 (±4.3) days of azathioprine commencement, was of mild severity and resolved within days of azathioprine withdrawal. Of the seven patients with azathioprine-related pancreatitis, four developed recurrent pancreatitis after commencing mercaptopurine. Overall, 43% of patients with prior azathioprine-related pancreatitis tolerated subsequent mercaptopurine therapy. There was no significant difference between those patients who did and did not tolerate mercaptopurine with respect to age, gender, disease distribution, or initiation timing. This data indicates that a sizeable proportion of people who develop pancreatitis with azathioprine therapy will tolerate subsequent mercaptopurine therapy. Azathioprine-associated pancreatitis should not be considered a strict contraindication to the subsequent use of mercaptopurine in patients with IBD.