Outcome of patients on azathioprine: a need for a better pre-treatment assessment and dosing guideline

Abstract

Background: Azathioprine (AZA) is a commonly used drug for the management of various rheumatologic disorders. Due to individual variation of the metabolism of AZA, related to genetic polymorphism of the thiopurine methyl transferase (TPMT), serious toxic effects can result if inappropriate dose is administered. AZA dosing according to patients TPMT status can reduce drug-induced morbidity and can be cost effective.

Aim: To determine the current local practice of AZA dosing, identify AZA-related toxicity and to compare the local practice with the British Society of Rheumatology (BSR) recommendations.

Methods: Retrospective review of patients on AZA for various rheumatologic conditions from inpatient (n=22) and outpatient (n=38) database at Middlemore Hospital, from January 2003 to January 2007. Data were collected on patient's demographics, treatment history including AZA dosing regimen, TPMT testing, drug-related toxicities and their management.

Results: The mean age was 53 years; 73% were females. 43% of European ethnicity; mean weight of patient was 75±25 kg. 42% had SLE, 22% had rheumatoid arthritis, and 13% had systemic vasculitis. Average initial dose of AZA prescribed was 100±37 mg. 45% developed AZA related toxicity. AZA was withdrawn in 35 % of patients due to drug-related side-effects and inefficacy.15% of the patients required dose reduction. TPMT status was tested in 6 (10%) patients; three had low TMPT level, needing dose reduction. BSR recommendation for AZA dosing was followed in 15% cases.

Conclusion: A significant proportion of the studied cohort of rheumatologic patients on AZA had drug-related toxicity resulting in discontinuation of AZA. Our data suggests that better pre-treatment assessment including TPMT testing and the practice of guideline based dosing regimen would reduce the incidence of undue side-effects and discontinuation of such treatment.