Toxic effects of azathioprine in rheumatoid arthritis. A national post-marketing perspective

Concerns about the short-term and long-term toxic effects of azathioprine (AZA) have limited its use. Accordingly, we surveyed 393 AZA-treated rheumatoid arthritis (RA) patients, who were recruited and enrolled through a nationwide call to rheumatologists. Findings in these patients were compared with the findings, retrieved from the databank of the American Rheumatism Association Medical Information System, on 153 similarly treated RA patients. All 546 patients were surveyed prospectively, using the Health Assessment Questionnaire and information abstracted from hospital records. The 2 groups were closely similar in clinical characteristics. The most frequently reported side effects of AZA treatment were nausea, vomiting, and leukopenia. Gastrointestinal intolerance accounted for nearly 60% of therapy interruptions in 95 patients. Of 81 hospitalizations for all causes, only 8 may have been related in part to AZA, and no deaths were attributed to AZA therapy. No lymphomas or leukemias were encountered and the overall frequency of neoplasms was not significantly different from that seen in RA patients receiving conventional therapy. As used in the treatment of RA, AZA has a surprisingly benign profile with relatively few serious therapeutic mishaps.