High dose intravenous methotrexate for refractory rheumatoid arthritis

Eight patients with active rheumatoid arthritis were given high dose intravenous methotrexate (MTX) (500 mg/m2) followed by oral leucovorin every 2 weeks for up to 6 months. All patients enrolled had previously failed conventional MTX therapy. Five patients completed 6 months of therapy. Three withdrew early, one due to inefficacy, one due to gastrointestinal intolerance and one due to sciatica requiring hospital admission. Fifty percent or greater improvements were seen in 5 of 8 clinical variables in those patients who completed 6 months of therapy. Six of 8 improvements achieved statistical significance at 24 weeks. Upon discontinuing therapy, patients flared within 8 to 12 weeks. Those who were maintained by low dose MTX after the high dose protocol were able to sustain their improvement throughout the subsequent 6 months of followup.