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Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review.
Rheumatology (Oxford) 2004; 43(3):267-71R

Abstract

OBJECTIVES

The folate antagonist methotrexate (MTX) has become established as the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA) but is commonly discontinued due to adverse effects. Adverse effects are thought to be mediated via folate antagonism. In this paper we summarize the current data on the use of folates as a supplement to MTX use in RA for the prevention of adverse effects and as a potential modulator of cardiovascular risk, and propose guidelines for standard practice.

METHODS

A Medline search was performed using the search terms "methotrexate", "folic acid", "folinic acid", "folate" and "homocysteine". Literature relevant to the use of folates as a supplement to MTX in the treatment of RA was reviewed and other papers referred to as references were explored.

RESULTS

The use of supplemental folates, including folic and folinic acid, in RA patients treated with MTX has been shown to improve continuation rates by reducing the incidence of liver function test abnormalities and gastrointestinal intolerance. Folate supplements do not appear to significantly reduce the effectiveness of MTX in the treatment of RA. Furthermore, supplemental folic acid offsets the elevation in plasma homocysteine associated with the use of MTX. This may in turn reduce the risk of cardiovascular disease, which is over-represented amongst patients with RA, and for which hyperhomocysteinaemia is now recognized as an independent risk factor.

CONCLUSIONS

We propose that folic acid supplements be prescribed routinely to all patients receiving MTX for the treatment of RA. We recommend a pragmatic dosing schedule of 5 mg of oral folic acid given on the morning following the day of MTX administration.

Authors+Show Affiliations

Department of Rheumatology, Ashford & St Peters NHS Trust, St Peter's Hospital, Guildford Road, Chertsey, Surrey KT16 0PZ, UK.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

14963199

Citation

Whittle, S L., and R A. Hughes. "Folate Supplementation and Methotrexate Treatment in Rheumatoid Arthritis: a Review." Rheumatology (Oxford, England), vol. 43, no. 3, 2004, pp. 267-71.
Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology (Oxford). 2004;43(3):267-71.
Whittle, S. L., & Hughes, R. A. (2004). Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology (Oxford, England), 43(3), pp. 267-71.
Whittle SL, Hughes RA. Folate Supplementation and Methotrexate Treatment in Rheumatoid Arthritis: a Review. Rheumatology (Oxford). 2004;43(3):267-71. PubMed PMID: 14963199.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. AU - Whittle,S L, AU - Hughes,R A, Y1 - 2004/01/06/ PY - 2004/2/14/pubmed PY - 2004/5/21/medline PY - 2004/2/14/entrez SP - 267 EP - 71 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 43 IS - 3 N2 - OBJECTIVES: The folate antagonist methotrexate (MTX) has become established as the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA) but is commonly discontinued due to adverse effects. Adverse effects are thought to be mediated via folate antagonism. In this paper we summarize the current data on the use of folates as a supplement to MTX use in RA for the prevention of adverse effects and as a potential modulator of cardiovascular risk, and propose guidelines for standard practice. METHODS: A Medline search was performed using the search terms "methotrexate", "folic acid", "folinic acid", "folate" and "homocysteine". Literature relevant to the use of folates as a supplement to MTX in the treatment of RA was reviewed and other papers referred to as references were explored. RESULTS: The use of supplemental folates, including folic and folinic acid, in RA patients treated with MTX has been shown to improve continuation rates by reducing the incidence of liver function test abnormalities and gastrointestinal intolerance. Folate supplements do not appear to significantly reduce the effectiveness of MTX in the treatment of RA. Furthermore, supplemental folic acid offsets the elevation in plasma homocysteine associated with the use of MTX. This may in turn reduce the risk of cardiovascular disease, which is over-represented amongst patients with RA, and for which hyperhomocysteinaemia is now recognized as an independent risk factor. CONCLUSIONS: We propose that folic acid supplements be prescribed routinely to all patients receiving MTX for the treatment of RA. We recommend a pragmatic dosing schedule of 5 mg of oral folic acid given on the morning following the day of MTX administration. SN - 1462-0324 UR - https://www.unboundmedicine.com/medline/citation/14963199/Folate_supplementation_and_methotrexate_treatment_in_rheumatoid_arthritis:_a_review_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/keh088 DB - PRIME DP - Unbound Medicine ER -