Azathioprine Hepatotoxicity is Uncommon in Patients with Rheumatic Diseases

Abstract

At present, there is no consensus regarding the utility of liver enzyme monitoring in rheumatology patients undergoing treatment with azathioprine (AZA). To further investigate this issue, we retrospectively reviewed for current or past use of AZA all patient records in our Disease Modifying Antirheumatic Drug (DMARD) clinic from May 1986 through September 1996. Information available from individual DMARD charts included AZA data (dates initiated, dose, indication for changing dose or stopping AZA), co-administered DMARDs, and aspartate aminotransferase (AST) serum values. In patients followed in the clinic through February 1994, serum alkaline phosphatase (AP) values additionally were available. Published reports of AZA hepatotoxicity in rheumatoid arthritis (RA) patients were found by a MEDLINE search, supplemented by a manual search of reference lists.We screened 429 patient records, and all patients who had received AZA at any time during the study period (n = 56) were identified for further review. The mean daily AZA dose was 96 mg (median = 100 mg/ day, range = 25-200 mg/day). All of the 56 patients had undergone routine periodic monitoring of serum AST while taking AZA (mean interval = 26 days); 30 of these patients additionally underwent monitoring of serum AP (mean interval = 24 days). Twenty-three (41%) of the patients had at least one episode of an abnormally elevated serum AST and/or AP while taking AZA. Only 1 of these 2 laboratory values was abnormal in 12 patients. The average time from AZA initiation to first appearance of an abnormal AST and/or AP value was 27 days (range = 7-62 days). During observation alone, all abnormal laboratory test results became normalized in 20 of 23 patients (87%) during the study period. There were no interventions in response to an abnormal laboratory value, and no patient experienced an adverse clinical outcome attributable to AZA hepatotoxicity during the 10-year study period.AZA use for rheumatic conditions may be associated with elevations in both the serum AST and/or AP values. Most of these elevations were transient, and none were clinically significant in our patient population. This study supports current American College of Rheumatology guidelines, which do not recommend routine periodic monitoring with liver enzyme tests in RA patients taking AZA. Furthermore, this study suggests that the utility of the baseline liver enzyme test in these patients is not well established.