SUPPLEMENTATION WITH FOLIC-ACID DARING METHOTREXATE THERAPY FOR RHEUMATOID-ARTHRITIS - A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective: To determine the effect of two different weekly doses of fo lic acid on the toxicity and efficacy of low-dose methotrexate therapy for rheumatoid arthritis. Design: Randomized, double-blind, placebo-c ontrolled study. Patients: 79 persons between 19 and 78 years of age w ho fulfilled the American Rheumatism Association's criteria for rheuma toid arthritis. Intervention: Participants were randomly assigned to v isually identical placebo or to 5 mg or 27.5 mg of folic acid each wee k. Measurements: Duration, intensity, and clinical severity of toxic e vents; efficacy (indices of joint tenderness and swelling and grip str ength); plasma and erythrocyte folate levels; and other laboratory var iables. Results: Polio acid supplementation at either dose did not aff ect the efficacy of methotrexate therapy as judged by joint indices an d patient and physician assessments of disease. Patients given folic a cid supplements had lower toxicity scores than did participants given placebo (P less than or equal to 0.001). Low blood folate levels and i ncreased mean corpuscular volumes were associated with substantial met hotrexate toxicity, whereas daily dietary intakes of more than 900 nmo l (400 mu g) of folic acid were associated with little methotrexate to xicity. Conclusions: Folic acid, an inexpensive vitamin, is safe in a broad range of doses and protects patients with rheumatoid arthritis w ho are taking methotrexate from toxicity while preserving the efficacy of methotrexate.