OBJECTIVE: To evaluate whether age and renal impairment affect the rate of side effects or expected efficacy of methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Data was pooled from 11 MTX clinical trials containing 496 patients treated withMTX. We evaluated those patients less than 60 years old and those in 5-year groupings of age over age 60. Using serum creatinine, weight, and age, we calculated creatinine clearance and placed patients into quartiles based on their baseline creatinine clearance. To evaluate efficacy, we used changes in American College of Rheumatology core set efficacy measures available in these 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 separately evaluated liver toxicities (twice normal elevation of AST or ALT), respiratory toxicity and severe toxicities. Intent-to-treat analyses were performed, adjusting for study of origin. Results were confirmed 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, > or = 70 years) were not at higher risk of side effects from MTX. However, patients with renal impairment had a higher overall rate of toxicity and were at higher risk of severe and respiratory toxicities than those whose creatinine clearances were at least 99.8 ml/min (reference group). The odds of severe toxicity were increased roughly 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.
RCT Entities:
OBJECTIVE: To evaluate whether age and renal impairment affect the rate of side effects or expected efficacy of methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Data was pooled from 11 MTX clinical trials containing 496 patients treated with MTX. We evaluated those patients less than 60 years old and those in 5-year groupings of age over age 60. Using serum creatinine, weight, and age, we calculated creatinine clearance and placed patients into quartiles based on their baseline creatinine clearance. To evaluate efficacy, we used changes in American College of Rheumatology core set efficacy measures available in these 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 separately evaluated liver toxicities (twice normal elevation of AST or ALT), respiratory toxicity and severe toxicities. Intent-to-treat analyses were performed, adjusting for study of origin. Results were confirmed 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, > or = 70 years) were not at higher risk of side effects from MTX. However, patients with renal impairment had a higher overall rate of toxicity and were at higher risk of severe and respiratory toxicities than those whose creatinine clearances were at least 99.8 ml/min (reference group). The odds of severe toxicity were increased roughly 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.