The Role of Methotrexate in Azathioprine and 6-Mercaptopurine-induced Pancreatitis in Inflammatory Bowel Disease Patients

Abstract

Purpose: Immunomodulators are frequently used in the treatment of inflammatory bowel disease (IBD). Although uncommon, azathioprine (AZA) and 6-mercaptopurine (6MP) can cause drug-induced pancreatitis, which prevents any future use of these medications. We propose that in these patients who require immunomodulator therapy, methotrexate could be used as an alternative when AZA or 6MP is contraindicated. In our study, we followed a series of patients who developed drug-induced pancreatitis on AZA or 6MP, and monitored the outcome after switching to methotrexate. Methods: Between 2008 and 2013, IBD patients with a diagnosis of pancreatitis induced by AZA or 6MP were identified from our prospectively maintained and institutional review board-approved IBD database. Demographic, clinical, and medication history were reviewed. Patients started on methotrexate were evaluated. Results: Eight patients (six female, two male, six Crohn's disease, two ulcerative colitis) were identified to have had AZA or 6MP induced pancreatitis. Other common etiologies were ruled out by negative testing at the onset of pancreatitis. Two required hospitalization, but all eight recovered without longterm complications. Five patients were started on methotrexate (three oral, two subcutaneous route). One of the five patients developed an increase in transaminases, and thereby discontinued its use. One patient developed a local reaction to the injection site that was controlled with antihistamines for initial doses and resolved with continued use of methotrexate. Another patient transitioned successfully from oral to subcutaneous route of administration due to nausea. None developed any further episodes of pancreatitis to date. Conclusion: Of the five patients who were started on methotrexate after AZA or 6MP induced pancreatitis, none had a recurrence of pancreatitis. One patient eventually discontinued methotrexate use due to an increase in transaminases. Although further studies will be needed to confirm safety across a larger group of patients, in our case series of IBD patients with drug-induced pancreatitis, methotrexate was used as an alternate immunomodulator without pancreatitis recurrence.