Influence of High-Dose Folic Acid on Methotrexate Efficacies and Safety in Japanese Rheumatoid Arthritis Patients

Abstract Backgrounds Folic acid dose at ≦5 mg/week has been recommended for rheumatoid arthritis (RA) patients to decrease risk of methotrexate adverse effects. However, higher doses of folic acid is used in some cases. We examined the influence of high-dose folic acid on methotrexate efficacies and safety in Japanese RA patients. Methods 502 RA patients of four hospitals prescribed methotrexate and folic acid were included. These patients were divided into two subgroups according to the threshold of folic acid dose by 5 mg/week. Basic patient characteristics, methotrexate doses, and the efficacies or adverse effects of methotrexate were retrospectively compared between the two patient subgroups. Results The frequency of folic acid use at doses higher than 5 mg/week was significantly different between the four hospitals (P<0.001). The prevalence of methotrexate adverse effects was not significantly different between the patients taking folic acid less and more than 5 mg/week. However, in the lower dose methotrexate subgroup (≦8 mg/week), the prevalence of patients exhibiting abnormal serum ALT concentrations in the patients using higher (>5 mg/week) dose of folic acid was significantly higher than that in the lower (≦5 mg/week) folic acid-treated subgroup (P=0.029). Folic acid dose between patients taking methotrexate less and more than 8 mg/week was not significantly different. Major conclusion Folic acid dose was dependent on the hospitals, while efficacies and hepatotoxicity of methotrexate was not basically different between patients taking less and more than 5 mg/week of folic acid.