LONG-TERM COMBINATION THERAPY OF REFRACTORY AND DESTRUCTIVE RHEUMATOID-ARTHRITIS WITH METHOTREXATE (MTX) AND INTRAMUSCULAR GOLD OR OTHER DISEASE-MODIFYING ANTIRHEUMATIC DRUGS COMPARED TO MTX MONOTHERAPY

Objective. To evaluate tolerability and efficacy of combination therap y with methotrexate (MTX)/parenteral gold or MTX/other disease modifyi ng antirheumatic drug (DMARD, d-penicillamine or chloroquine) in compa rison with MTX monotherapy in patients with longstanding destructive a ctive rheumatoid arthritis (RA).Methods. In an open prospective trial all consecutive MIX-naive patients with active RA starting MTX treatme nt alone or in combination between January 1980 and December 1987, aft er failing one or more DMARD, were followed at regular intervals up to 108 months. Evaluations included the number of swollen joints (0-32), grip strength, patient assessment of pain and mobility, erythrocyte s edimentation rate (ESR), C-reactive protein (CRP), and hemoglobin. Gro up 1, treated with MTX monotherapy (n = 97), was compared with Group 2 , with combination therapy MTX/parenteral gold (n = 126) and Group 3 w ith MTX + other DMARD (n = 48). Results. There were no significant dif ferences between the groups in mean age (59/57/56 yrs), disease durati on (9.6/7.7/8.3 yrs), seropositivity (80/88/82%), or ACR anatomical di sease stage (2/3 in stage III and IV). The number of swollen joints (1 6.8/19.3/16.1 of 32) and the CRP (4.4/5.1/4.7 mg/dl) was significantly greater in Group 2; other disease activity variables were not signifi cantly different. The mean MTX dose at baseline (mostly parenteral) wa s 16.8/17.0/12.8 mg and could be reduced to around 12 mg (predominantl y oral) in the 3 groups. Frequency of adverse events (80/83/88%), natu re of clinical (nausea, hair loss, stomatitis) and laboratory (liver e nzyme elevation, slight proteinuria) side effects, and withdrawal rate for side effects (20.6/15.0/12.5%) were not significantly different b etween the groups. After 5 years 54/54/80% of patients continued their treatment. All efficacy variables improved significantly (p < 0.001) in all groups without significant intergroup difference. Improvement > 50% in the ESR was achieved in 63/68/41% and in the swollen joint cou nt in 70/85/48% of patients after 3 years. The number of patients taki ng oral steroids decreased from 63/59/65% to 22/31/48% after 3 years. In half the patients hemoglobin increased by at least 1 g/dl. Conclusi on, Combination therapy of MTX with parenteral gold or other DMARD is effective in reducing clinical and biochemical disease activity in pat ients with longstanding destructive RA with no greater risk of toxicit y compared with MTX alone; our study however, did not show clear advan tages of combination therapy versus monotherapy for effectiveness.