Methotrexate hepatotoxicity in patients with rheumatoid arthritis

ABSTRACT

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. 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. 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]. 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