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The Effect of Folate Supplementation on Methotrexate Efficacy and Toxicity in Psoriasis Patients and Folic Acid Use by Dermatologists in the USA

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Abstract

Background

Methotrexate (MTX) is an effective treatment for psoriasis but its use is limited by its toxicity. Folate supplementation can be used to reduce the adverse effects of MTX, though this may impact efficacy. The frequency of folic acid supplementation is not well characterized.

Purpose

The objective of this study was to review the literature involving the use of folate in patients (in particular those with psoriasis) treated with MTX and analyze trends in folic acid use.

Methods

We searched PubMed from 1 May 1989 through 1 April 2012 using the terms ‘folic acid,’ ‘folinic acid,’ ‘folate,’ ‘supplementation,’ and ‘methotrexate.’ We also used the National Ambulatory Medical Care Survey (NAMCS) database to collect data regarding trends in MTX use and folic acid supplementation by physicians in the USA from 1993 through 2009. We assessed data including the number of MTX visits, rate of folic acid use, diagnoses, physician specialty, and demographics of patients. We used linear regression to analyze the change in folic acid use over time.

Results

Twenty-six published trials were included addressing folic acid supplementation with MTX. The majority found a benefit to folic acid supplementation, but there were only seven studies in psoriasis. Dermatologists were among the highest prescribers of MTX, and psoriasis was commonly treated with MTX. Folic acid supplementation significantly increased over this time period (p < 0.0001). However, dermatologists ranked lowest for their folate use, co-prescribing folate to only 9.1 % of MTX-treated patients.

Limitations

In contrast to rheumatoid arthritis, there is a scarcity of literature describing the effect of folate on MTX toxicity and efficacy in psoriasis patients. NAMCS data only included outpatient visits to non-federally employed physicians, and there is the possibility of healthcare providers not documenting over-the-counter folic acid usage. Lastly, doses of MTX and folic acid were not recorded in the database.

Conclusion

Dermatologists were the least likely specialists to supplement MTX with folic acid. The evidence for supplementation of folic acid is mixed. The literature confirms a reduction in the adverse effects of MTX but less strongly that there may be a reduction in efficacy too. Keeping in mind the potential for folate to reduce MTX efficacy, folic acid supplementation should be considered in MTX-treated patients.

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Acknowledgments

The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Dr. Feldman is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, and Bristol Myers Squibb. Dr. Feldman has received grants from Galderma, Astellas, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol Myers Squibb, Stiefel/GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceuticals, Celgene, Basilea, and Anacor and has received stock options from Photomedex. He is owner of http://www.DrScore.com and a founder of Causa Research. Ms. Huang receives fellowship support from the National Psoriasis Foundation/USA. Mr. Al-Dabagh, Mr. Davis, and Dr. Kinney have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Dermatology, Center for Dermatology Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1071, USA

    Amir Al-Dabagh, Scott A. Davis, Megan A. Kinney, Karen Huang & Steven R. Feldman

  2. Department of Pathology, Center for Dermatology Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Steven R. Feldman

  3. Department of Public Health Sciences, Center for Dermatology Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Steven R. Feldman

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  1. Amir Al-Dabagh
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Correspondence to Amir Al-Dabagh.

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Al-Dabagh, A., Davis, S.A., Kinney, M.A. et al. The Effect of Folate Supplementation on Methotrexate Efficacy and Toxicity in Psoriasis Patients and Folic Acid Use by Dermatologists in the USA. Am J Clin Dermatol 14, 155–161 (2013). https://doi.org/10.1007/s40257-013-0017-9

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