Azathioprine: an update on clinical efficacy and safety in inflammatory bowel disease

Background: The approval of azathioprine (AZA) for the long-term therapy of patients with Crohn's disease in The Netherlands. Methods: Review and upda te of the literature on clinical efficacy and safety of AZA in inflammatory bowel disease. Results: AZA and its metabolite 6-mercaptopurine (6-MP) are effective in the treatment of active Crohn's disease. However, the onset o f the clinical response is delayed, requiring combination with other active medication in the early phase of treatment. Maintenance therapy with AZA/6 -MP is also effective in the prevention of relapses in patients with Crohn' s disease in remission. Indications for AZA/6-MP therapy further include re fractory, fistulizing and steroid-dependent Crohn's disease. It is not know n whether or when AZA/6-MP can be withdrawn in patients in long-term remiss ion, but most clinicians discontinue therapy after 3-5 years. Although fewe r data are available, AZA/6-PM appears to be effective also in the therapy of patients with ulcerative colitis. Side effects of AZA/6-MP occur in abou t 15% of patients and include skin rash, pancreatitis and hepatitis, dose-r elated neutropenia and thrombocytopenia, and risk of increased occurrence a nd severity of infections. Recent data suggest that the risk of malignancy, other than colorectal cancer, is not increased. Safety in pregnancy has no t been studied extensively, but no increased prevalence of birth defects ha s been reported. Conclusions: AZA/6-MP therapy is efficacious in patients w ith active Crohn's disease, but the drug is especially valuable in the long -term treatment of patients with Crohn's disease and ulcerative colitis. Dr ug-related side effects are frequent and require discontinuation or dose-re duction of the AZA/6-MP therapy. Due to an increased risk of infections sec ondary to myelosuppression, careful follow-up is mandatory. Insufficient da ta are available on safety in pregnancy and on the risk of malignancies, bu t the limited data available in patients with inflammatory bowel disease ap pear to be reassuring.