Folate supplementation and MTX treatment in RA: a review

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Rheumatology Advance Access originally published online on January 6,

2004

Rheumatology 2004; 43: 267-271

Rheumatology Vol. 43 No. 3 © British Society for Rheumatology 2003;

all rights reserved

Review

Folate supplementation and methotrexate treatment in rheumatoid

arthritis: a review

S. L. Whittle and R. A.

Department of Rheumatology, Ashford & St s NHS Trust, Chertsey, UK.

Correspondence to: R. A. , Department of Rheumatology, St 's

Hospital, Guildford Road, Chertsey, Surrey KT16 0PZ, UK. E-mail:

Rod.@...

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.

KEY WORDS: Methotrexate, Folic acid, Folinic acid, Homocysteine.

http://rheumatology.oupjournals.org/cgi/content/abstract/43/3/267

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