Background: Methotrexate is a potent immunosuppressant which in theory could reduce relapse rates and delay disease progression in multiple sclerosis (MS). Subsequently, clinical trials of methotrexate have been conducted in people with MS.
Objectives: To identify and summarise the evidence that methotrexate is beneficial and safe for people with MS.
Search strategy: We searched the Cochrane MS Group trials register (searched December 2003), the Cochrane Central Register of Controlled Trails (The Cochrane Library Issue 4, 2003), MEDLINE (Pub Med) (January 1966 to June 2001), EMBASE (January 1988 to June 2001), and reference lists of articles. We also contacted trialists and pharmaceutical companies.
Selection criteria: Randomised controlled trials of methotrexate for the prevention of relapses and disease progression in MS.
Data collection and analysis: Two reviewers (OG, GM, ) independently selected articles for inclusion, assessed the trials' quality and extracted the data. Authors of one trial were contacted to obtaining missing information.
Main results: One trial involving 60 participants with chronic progressive multiple sclerosis was included. The trial showed a non-significant reduction in sustained EDSS progression and number of relapses in favour of methotrexate therapy. There was no difference in time to first relapse and no data on relapse rate. Minor side-effects were reported frequently in both methotrexate (87.1%) and placebo groups (89.7%), but there were no major side-effects.
Reviewers' conclusions: In progressive MS, the single included trial reveals a non-significant trend in reduction of sustained EDSS progression and number of relapses in favour of methotrexate. A trial of methotrexate in relapsing remitting MS showed non-significant trends in favour of methotrexate but was excluded on methodological grounds. Before drawing further conclusions regarding the efficacy of methotrexate in MS, further trials are required.