METHOTREXATE THERAPY IN RHEUMATOID-ARTHRITIS - A 2 YEAR PROSPECTIVE FOLLOW-UP

One hundred and thirty seven rheumatoid arthritis (RA) patients refractory to D-penicillamine and some of them (15%) refractory to other slow active drugs were treated with oral methotrexate (MTX) (10-15mg weekly). After 12-24 months of treatment, 94 and 74 patients respectively showed a significant improvement as judged by duration of morning stiffness (p<0.0001), grip strength (p<0.0001), degree of joint swelling (p<0.01) and tenderness (p<0.0001) compared to pre-treatment values. This clinical improvement was also associated with a decrease of erythrocyte sedimentation rate (p<0.0001), decrease of C-reactive protein (p<0.0001) and with improvement of anaemia (p<0.05). No changes were seen in rheumatoid factor titres. Seventy-four of the patients were followed for up to 24 months. Thirty-one of them (23%) had complete remission and 43 (31%) had an excellent response. Adverse drug reaction during MTX therapy included: elevated liver enzymes in 34 patients, mucosal ulcers in 21, nausea and vomiting in 8, diarrhoea in 4, leukopenia in 2, interstitial pneumonitis in one, intestinal bleeding in one and finally septic arthritis in another patient. The majority of these side effects were resolved without sequelae. However, 15 patients (11%) with adverse drug reactions had to discontinue the treatment. Forty-one of our patients who received a cumulative mean dose of MTX of 1550.5±235.5 mg underwent a percutaneous liver biopsy. Ten patients had normal tissue, 12 had minimal changes, 13 nonspecific changes and 6 patients had mild fibrosis. We conclude that MTX therapy in refractory RA patients appears to be effective, but requires close monitoring for toxicity. Hepatotoxicity with fibrosis and cirrhosis due to long term MTX therapy may be relatively uncommon in RA patients. © 1990 Springer-Verlag.