THE EFFECT OF AGE AND RENAL-FUNCTION ON THE EFFICACY AND TOXICITY OF METHOTREXATE IN RHEUMATOID-ARTHRITIS

Objective. To evaluate whether age and renal impairment affect the rat e of side effects or expected efficacy of methotrexate (MTX) in rheuma toid arthritis (RA). Methods. Data was pooled from 11 MTX clinical tri als containing 496 patients treated with MTX. We evaluated those patie nts less than 60 years old and those in 5-year groupings of age over a ge 60. Using serum creatinine, weight, and age, we calculated creatini ne clearance and placed patients into quartiles based on their baselin e creatinine clearance. To evaluate efficacy, we used changes in Ameri can College of Rheumatology core set efficacy measures available in th ese trials. To quantify side effects, we scored each side effect based on a modified Fries toxicity score and assigned each patient a score based on the worst side effect experienced during the trial. We also s eparately evaluated liver toxicities (twice normal elevation of AST or ALT), respiratory toxicity and severe toxicities. Intent-to-treat ana lyses were performed, adjusting for study of origin. Results were conf irmed by placebo controlled trials, comparing MTX and placebo treated patients. Results. Neither age nor renal impairment had any effect on the efficacy of MTX. Those in the oldest age groups (65-69 years, grea ter than or equal to 70 years) were not at higher risk of side effects from MTX. However, patients with renal impairment had a higher overal l rate of toxicity and were at higher risk of severe and respiratory t oxicities than those whose creatinine clearances were at least 99.8 mI /min (reference group). The odds of severe toxicity were increased rou ghly 4-fold in those with renal impairment. Conclusion. Among clinical trial patients, age does not affect MTX efficacy or the rate of side effects. Renal impairment, however, increases the risk of side effects .