title: Efficacy of methotrexate in ulcerative colitis: failure or promise.
abstract: BACKGROUND
  Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized controlled trials have demonstrated the efficacy of parenteral methotrexate in Crohn's disease (CD). We performed a systematic review of the efficacy of methotrexate in ulcerative colitis (UC) and discuss the results in the context of the known pharmacokinetics and adverse events of methotrexate therapy in inflammatory bowel diseases and other inflammatory conditions.
  
  
  METHODS
  We performed a systematic review of the literature in Medline, Embase, and Web of Science. All publications describing patients with UC treated with methotrexate were included.
  
  
  RESULTS
  We identified 12 studies or retrospective case series and 5 meeting abstracts that met the inclusion criteria. Only 1 study reported a prospective randomized placebo-controlled trial using methotrexate at a dose of 12.5 mg orally with no significant clinical benefit. However, the majority of uncontrolled retrospective analyses suggest a clinical response to methotrexate therapy in a range of 30%-80% when the drug is applied by parenteral route in doses between 20-25 mg.
  
  
  CONCLUSIONS
  The only randomized controlled trial of methotrexate in UC employed oral dosing and doses lower than those shown to be effective in CD and did not demonstrate efficacy, whereas uncontrolled, retrospective studies using doses and routes of administration similar to those employed in CD suggest benefit. Well-designed, prospective, placebo-controlled trials of methotrexate in UC are needed.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA. hherf@med.unc.edu
authors.forename: Hans H
authors.initials: HH
authors.lastname: Herfarth
authors.forename: Mark T
authors.initials: MT
authors.lastname: Osterman
authors.forename: Kim L
authors.initials: KL
authors.lastname: Isaacs
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
mesh_terms: D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005260:Female; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D005493:Folic Acid Antagonists; D008727:Methotrexate