LOW-DOSE (7.5-MG) ORAL METHOTREXATE REDUCES THE RATE OF PROGRESSION IN CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS

A randomized, double-blinded, placebo-controlled, clinical trial of lo w-dose, weekly, oral methotrexate was performed in 60 patients with cl inically definite chronic progressive multiple sclerosis (MS) attendin g a referral-based outpatient MS clinic. Study patients were 21 to 60 years old with a disease duration of longer than 1 year. Patients' Exp anded Disability Status Scale scores were 3.0 to 6.5 (ambulatory with moderate disability). Patients were first stratified by Expanded Disab ility Status Scale scores, 3.0 to 5.5 and 6.0 to 6.5, and then were ra ndomized to receive methotrexate or placebo treatment. Treatment consi sted of weekly, oral, low-dose (7.5 mg) methotrexate or identical plac ebo for 2 years, followed by observation for as long as 1 year. A comp osite outcome measurement instrument was used and consisted of (1) Exp anded Disability Status Scale, (2) ambulation index, (3) Box and Block Test, and (4) 9-Hole Peg Test. Failure of therapy was Indicated by a designated change that was sustained for more than 2 months in one or more components of this composite measure. Significantly less progress ion of impairment as measured by validated tests of upper-extremity fu nction was observed in the methotrexate treatment group in the absence of clinically significant toxicity. We conclude that low-dose, weekly , oral methotrexate offers a new, relatively nontoxic treatment option foe patients with chronic progressive MS.