[Reducing toxicity of methotrexate with folic acid]

Methotrexate is considered to have the best ratio of efficacy to toxicity of the disease modifying antirheumatic drugs. Recently it has been shown to enhance the life expectancy of patients with rheumatoid arthritis. Some 30-60% of RA patients discontinue MTX treatment within 1 year because of side-effects. In this review, the current data about supplementation with folate or folinic acid and their effect on the toxicity and efficacy of low-dose methotrexate therapy are analysed.

A Medline search was performed using "folate", "folic acid", "folinic acid", "homocysteine", "methotrexate", "cardiovascular", "heart infarction" and "rheumatoid arthritis" as search terms. The relevant literature was reviewed and other papers referred to as references were explored.

Both folate and folinic acid reduce methotrexate toxicity and the discontinuation rate, and decrease methotrexate-induced hyperhomocysteinemia. Folate is less expensive, more secure and easier to handle than folinic acid. The efficacy of methotrexate probably decreases slightly, but the benefit outweighs the risk. Folate supplementation should, therefore, be routinely prescribed to every patient taking low-dose methotrexate.