Thiopurine-induced Myelotoxicity in Patients with Inflammatory Bowel Disease: a Review

Aim: Probably, the most important and potentially lethal adverse event of azathioprine (AZA) and mercaptopurine (MP) is myelosuppression. Our aim was to conduct a review of AZA/MP-induced myelotoxicity in inflammatory bowel disease (IBD) patients.

Methods: Bibliographical searches were performed in MEDLINE/EMBASE. The studies evaluating thiopurine-induced myelotoxicity in patients with IBD were reviewed. The cumulative incidence and the incidence rate of AZA/MP-induced myelotoxicity were calculated by a meta-analysis.

Results: In total, 66 studies (8,302 patients) were included. The cumulative incidence of AZA/MP-induced myelotoxicity was 7% (95% confidence interval [CI] 6-8%). The incidence rate (per patient and year of treatment) of the drug-induced myelotoxicity was 3% (95% CI 3-4%). The risk was roughly similar with AZA and with MP (7%vs 9%). The duration of AZA/MP treatment in patients with myelotoxicity ranged from 12 days to 27 yr. The cumulative incidence of infections among AZA/MP-induced myelotoxicity patients was 6.5%. The cumulative incidence of severe myelotoxicity was 1.1% (incidence rate 0.9%). Three deaths were reported due to myelotoxicity (cumulative incidence 0.06%, 95% CI 0.02-0.17%). The risk of death among patients who developed myelotoxicity was 0.94% (95% CI 0.32-2.70%).

Conclusion: The incidence rate of myelotoxicity in IBD patients receiving AZA/MP is approximately 3% per patient and year of treatment. Although bone marrow toxicity may develop at any time after starting the therapy, this happens more frequently during the first months. The incidence rate of severe myelotoxicity is less than 1% per patient and year of treatment, and the mortality risk is less than 0.1% (which means that the risk of death among IBD patients who develop myelotoxicity is approximately 1%).