METHOTREXATE IN RHEUMATOID-ARTHRITIS - FOLATE SUPPLEMENTATION SHOULD ALWAYS BE GIVEN

Methotrexate is now the disease-modifying antirheumatic drug prescribe d most frequently For the treatment of rheumatoid arthritis. Methotrex ate is an antifolate that inhibits methylation reactions and reactions of amino acid, purine and pyrimidine metabolism. Toxic manifestations of methotrexate administration for rheumatoid arthritis (at relativel y low doses compared with those used in cancer chemotherapy) include c ytopenias, gastrointestinal intolerance, liver disease, pulmonary inju ry, central nervous system dysfunction, skin rashes and nodulosis. Del ayed wound healing and increased risk for infections with opportunisti c organisms also occur. Some of these toxic manifestations respond to supplementation with folates [folic acid or folinic acid (calcium foli nate)]. The folate status of patients has been shown to be impaired af ter prolonged treatment with methotrexate, and poor baseline folate st atus is an independent risk factor for subsequent toxicity. Numerous s tudies have now documented that folic acid, even in high doses, and mo derate doses of folinic acid are beneficial in preventing methotrexate : toxicity without affecting efficacy. In this article we present guid elines and rationale for monitoring methotrexate therapy, and guidelin es for folate supplementation during methotrexate therapy for rheumato id arthritis. It is our recommendation that folic acid should be empir ically supplemented in all patients at the initiation of methotrexate therapy. This regimen is associated with a high benefit : risk ratio a nd is likely to be cost effective.