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Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review

S L Whittle1, R A Hughes

  • 1Department of Rheumatology, Ashford & St Peters NHS Trust, St Peter's Hospital, Guildford Road, Chertsey, Surrey KT16 0PZ, UK.

Rheumatology (Oxford, England)
|February 14, 2004
PubMed
Abstract

Insights

Supplementing methotrexate (MTX) with folic acid in rheumatoid arthritis (RA) patients improves drug adherence by reducing adverse effects. This strategy also helps lower cardiovascular risk by managing homocysteine levels.

Area of Science:

  • Rheumatology
  • Pharmacology
  • Nutritional Science

Background:

  • Methotrexate (MTX) is a primary disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA).
  • Adverse effects of MTX, potentially due to folate antagonism, often lead to treatment discontinuation.
  • Cardiovascular disease risk is elevated in RA patients, with hyperhomocysteinemia as a contributing factor.

Purpose of the Study:

  • To review current data on folate supplementation with MTX in RA.
  • To assess the impact of folates on MTX-related adverse effects.
  • To evaluate the role of folate supplementation in mitigating cardiovascular risk in RA patients.

Main Methods:

  • A comprehensive Medline search was conducted using keywords related to methotrexate, folic acid, folinic acid, folate, and homocysteine.
  • Literature focusing on folate supplementation in MTX-treated RA patients was reviewed.
  • References from relevant papers were also explored to gather additional data.

Main Results:

  • Folate supplementation (folic and folinic acid) significantly improves MTX continuation rates in RA patients.
  • Supplements reduce the incidence of liver function abnormalities and gastrointestinal intolerance.
  • Folic acid supplementation counteracts MTX-induced elevations in plasma homocysteine, potentially reducing cardiovascular risk without compromising MTX efficacy.

Conclusions:

  • Routine prescription of folic acid supplements is recommended for all RA patients on MTX therapy.
  • A recommended dosage is 5 mg of oral folic acid daily, taken the morning after MTX administration.
  • This approach aims to enhance treatment adherence and manage associated cardiovascular risks.

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