REVIEW - Effect of folic or folinic acid supplementation on MTX-associated safety and efficacy in inflammatory disease

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Br J Dermatol. 2009 Mar;160(3):622-8. Epub 2008 Oct 20.

Effect of folic or folinic acid supplementation on

methotrexate-associated safety and efficacy in inflammatory disease: a

systematic review.

Prey S, C.

Department of Dermatology, Sabatier University and Purpan

Hospital, 31 059 Toulouse cedex 9, France.

Abstract

BACKGROUND: Methotrexate is a folic acid antagonist widely used for

the treatment of inflammatory disorders for more than 50 years.

Methotrexate is a standard systemic therapy for severe psoriasis and

rheumatoid arthritis. Folic acid supplementation has been advocated to

limit the toxicity of methotrexate on blood cells, gastrointestinal

tract and liver. However, there is still controversy regarding the

usefulness of folic acid supplementation.

OBJECTIVES: We sought to assess the evidence for the efficacy of folic

acid supplementation in patients treated with methotrexate for

inflammatory diseases. We also investigated whether folic acid

supplementation may decrease the efficacy of methotrexate.

METHODS: Cochrane and MEDLINE databases were systematically searched.

Randomized controlled trials in patients treated with methotrexate for

rheumatoid arthritis or psoriasis with or without arthritis were

included. Study selection, assessment of methodological quality, data

extraction and analysis were carried out by two independent

researchers. We selected double-blind randomized placebo-controlled

trials. Analysis was performed for each subgroup of side-effects:

gastrointestinal, mucocutaneous, haematological and hepatic.

RESULTS: Six randomized controlled trials met the inclusion criteria,

with a total sample of 648 patients. There were 257 patients in the

placebo group, 198 patients treated with folic acid, and 193 patients

treated with folinic acid. The statistical analysis showed a

significant reduction of 35.8% of hepatic side-effects induced by

methotrexate for patients with supplementation with folic or folinic

acid (95% confidence interval -0.467 to -0.248). There was no

statistical difference for mucocutaneous and gastrointestinal

side-effects although there was a trend in favour of supplementation.

The effect of supplementation on haematological side-effects could not

be assessed accurately due to a low incidence of these events in the

population studied. We were unable to analyse the effect of

supplementation on the effectiveness of methotrexate, as markers of

activity used in each study were not comparable.

CONCLUSIONS: Supplementation with folic acid is an effective measure

to reduce hepatic adverse effects associated with methotrexate

treatment. There is no difference between folinic acid and folic acid,

but the lower cost of the latter promotes its use.

PMID: 18945303

http://www.ncbi.nlm.nih.gov/pubmed/18945303

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