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Efficacy of methotrexate in ulcerative colitis: Failure or promise

Herfarth, Hans H. MD, PhD1,*; Osterman, Mark T. MD2; Isaacs, Kim L. MD, PhD1; Lewis, James D. MD, MSCE2; Sands, Bruce E. MD, MS3

doi: 10.1002/ibd.21246
Clinical Reviews: Efficacy of Methotrexate in UC: Clinical Reviews

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.

Materials and 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. Inflamm Bowel Dis 2010

1Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina

2Division of Gastroenterology and the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania

3MGH Crohn's and Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

*Reprints: Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Bioinformatics Bldg., CB#7080, Chapel Hill, NC, 27599


Received for publication 28 December 2009; Accepted 28 December 2009.

Published online 23 February 2010 in Wiley InterScience (

Grant sponsor: National Institutes of Health; Grant Number: 1U34DK084511-01; Grant sponsor: Crohn's and Colitis Foundation of America (CCFA).

© Crohn's & Colitis Foundation of America, Inc.
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