Methotrexate Hepatotoxicity in Patients with Rheumatoid Arthritis

BACKGROUND Increases in aminotransferases (transaminitis) are potential major adverse reactions seen with long-term use of methotrexate (MTX). The aim of this study, therefore was to evaluate the incidence of MTX induced hepatotoxicity and its risk factors among rheumatoid arthritis (RA) patients. METHODS This retrospective study described 286 patients with RA who received ≥ 7.5 mg MTX weekly in an academic rheumatology clinic over a 15 year period. The results of serial liver function tests, concurrent MTX dose, cumulative dose and use of hepatotoxic drugs were collected and statistically analyzed according to a consecutive elevation in aminotransferases which occurred over at least a two week interval. RESULTS During the study period, 286 patients (84.4% female) with mean age of 46.6±12.7 years (18-84 years) were enrolled. Transaminitis occurred among 23.7% of patients (incidence: 6.9 per 100 person-years) during 40.5±34.6 month's exposure to MTX (989.6 person-years). The time difference between onset of therapy and occurrence of transaminitis was 22.1±22.0 months. The only significant factor related to the occurrence of transaminitis was the duration of MTX therapy. The average duration of treatment among patients with transaminitis (59.6±42.3 months) was greater than those with no transaminitis (p<0.001). The cumulative dose of MTX was significantly related to the occurrence of transaminitis (p<0.001). CONCLUSION MTX hepatotoxicity is a common complication of long-term treatment with MTX. It is associated with mild liver enzyme elevation and related to the duration of therapy.