title: The effect of folate supplementation on methotrexate efficacy and toxicity in psoriasis patients and folic acid use by dermatologists in the USA.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Center for Dermatology Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1071, USA. axa499@case.edu
authors.forename: Amir
authors.initials: A
authors.lastname: Al-Dabagh
authors.forename: Scott A
authors.initials: SA
authors.lastname: Davis
authors.forename: Megan A
authors.initials: MA
authors.lastname: Kinney
authors.forename: Karen
authors.initials: K
authors.lastname: Huang
authors.forename: Steven R
authors.initials: SR
authors.lastname: Feldman
mesh_terms: D003880:Dermatology / Q000639:trends; D005492:Folic Acid / Q000627:therapeutic use*; D005493:Folic Acid Antagonists / Q000009:adverse effects*; D005494:Folic Acid Deficiency / Q000517:prevention & control*; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects*; D011565:Psoriasis / Q000188:drug therapy*; D014481:United States
chemical_list: D005493:Folic Acid Antagonists; D005492:Folic Acid; D008727:Methotrexate