Safety Profile of Azathioprine in Inflammatory Bowel Disease

Abstract

Background: Azathioprine (AZA) remains a fundamental pharmacological agent in the treatment of chronic inflammatory bowel disease, particularly in resource-limited settings where biotherapies are less accessible. Despite its therapeutic efficacy, AZA is associated with significant adverse effects, necessitating rigorous monitoring. Objective: The main aim of our work is to assess the safety profile of azathioprine in Moroccan IBD patients by analyzing the incidence, nature, and temporality of adverse events in order to optimize its benefit-to-risk ratio in clinical practice. Methods: We conducted a retrospective, cross-sectional study over an 11-year period (2013-2024) at the Hassan II University Hospital in Fez, Morocco. A total of 250 patients with IBD treated with AZA were included in the analysis. Data were extracted from medical records and included demographic, clinical, and therapeutic variables. Adverse events were carefully recorded and analyzed according to frequency, patient profile, and time of onset. Resu lts: Of the 250 patients included, 62 (24.8%) experienced adverse events requiring temporary or permanent discontinuation of AZA. Hematological toxicity was the most frequent complication, affecting 29 patients (46.8%), followed by digestive intolerance in 15 patients (24.2%), hepatotoxicity in 11 patients (17.7%), pancreatitis in 4 patients (6.5%), and allergic reactions in 3 patients (4.8%). A slightly higher incidence of adverse events was observed in women than in men (56.4% vs. 43.6%). The median time to onset of adverse events varied, with allergic reactions occurring most rapidly (5 days), followed by hematological toxicity (17 days), hepatotoxicity (28 days), and pancreatitis (36 days). A total of 29 patients were re-exposed to AZA, of whom 11 (37.9%) experienced a recurrence of adverse events. Of these, 6 developed hematological toxicity, 3 developed hepatotoxicity, and 2 developed digestive intolerance. In addition, 15 patients who had discontinued AZA were placed on 6-mercaptopurine (6-MP), 10 of whom tolerated this treatment well, while 5 developed new adverse events, mainly allergic reactions and hematological toxicity. Conclusion: AZA remains an essential therapeutic option for IBD in Morocco, but its narrow therapeutic index requires rigorous monitoring. Hematological toxicity emerged as the most frequent complication, underlining the need for an individualized approach to treatment. Future research should explore the value of genetic screening and alternative dosing strategies to reduce toxicity while maintaining therapeutic efficacy.