Twenty-nine patients participated in a prospective study of the safety and 
efficacy of oral methotrexate in the treatment of refractory rheumatoid 
arthritis. Patients received a mean dosage of 12.4 mg weekly over a mean 
duration of 29.1 months. All patients had liver biopsies at baseline, 2 years, 
and annually thereafter. Patients improved significantly by all clinical 
measures of efficacy after 1 month; maximum improvement tended to occur after 
approximately 6 months of therapy. Radiographs showed improvement of erosive 
disease in 7 of 11 patients measured. There was a significant reduction in mean 
prednisone dosage. Four patients required an increase in the dosage of 
methotrexate after prolonged therapy, because of declining clinical response. 
Toxicity was noted at some time in 26 of 29 patients (90%), but reactions 
universally became mild and tolerable after adjustment of the dosage. No 
significant hepatotoxicity was found in 60 sequential liver biopsies, although 
elevated transaminase levels were noted at some time in 20 of 29 patients (70%).