A Survey of Canadian Gastroenterologists about the Use of Methotrexate in Patients with Crohn’s Disease

Abstract

BACKGROUND: Methotrexate (MTX) is effective in remission induction and maintenance in steroid-dependent Crohn's disease (CD), but is often considered to be a second-line immunosuppressive agent, to be used in cases of failure or intolerance to azathioprine (AZA) or 6-mercaptopurine (6-MP). This may be related to concerns about hepatotoxicity, but this adverse effect is rare in monitored CD patients taking MTX. Still, there are no guidelines for monitoring patients with CD on MTX, and physicians must decide based on rheumatological literature about how to monitor their patients.PURPOSE: To determine the patterns of MTX use in patients with CD by Canadian gastroenterologists, examining the reasons for choosing MTX versus AZA/6-MP, the doses and routes of administration of MTX, and how patients on MTX are monitored, including the use of liver biopsy.METHODS: A self-report survey was sent to physician members of the Canadian Association of Gastroenterology, with a second mailing three months later to increase response rate.RESULTS: Of 490 surveys mailed, a 54.9% response rate was achieved. Of adult gastroenterologists, 60.7% stated they never use MTX as a first-line immunosuppressive agent, and 33.3% never use MTX at all. The most common reasons for choosing MTX were a contraindication to the use of AZA/6-MP (43.7%) and patient preference (22.5%). MTX is used intramuscularly in 41.5%, subcutaneously in 31.8%, and orally in 26.7% of patients. The most common dose used for remission induction was 25 mg/week (84.2%; range 7.5 mg/week to 50 mg/week; three responders used more frequent dosing than weekly) and for remission maintenance was 15 mg/week (55.4%; range 7.5 mg/week to 50 mg/week; three responders used more frequent dosing than weekly). Most responders checked a liver profile and complete blood count at baseline and serially. Of those who used MTX, 26.5% routinely performed liver biopsy after an accumulated dose of MTX had been taken (usually 1 g to 2 g), 57.7% sometimes performed liver biopsy, and 16.8% never performed liver biopsy. Of pediatric gastroenterologists, 17.6% never used MTX, but those who used it prescribed it subcutaneously (80.0%) more often than intramuscularly (17.5%) or orally (2.5%).CONCLUSIONS: MTX was used as a first-line immunosuppressive agent in patients with CD by a minority of Canadian gastroenterologists. When used, there is variability in how MTX is prescribed and monitored. Although hepatotoxicity is rare, liver biopsy was performed frequently and probably often unnecessarily.