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.