Combination therapy in rheumatoid arthritis



Many Rheumatologists have been reluctant to accept ongoing disease in patients with rheumatoid arthritis. In recent years there  has been a tendency for Rheumatologists to treat Rheumatoid arthritis aggressively, as evidence now available, suggests that disease modifying drugs used early may alter the course of the disease. In addition it is now accepted the rheumatoid arthritis is not a benign disease, but has considerable morbidity, and in fact has a mortality approximating that of triple vessel coronary artery disease. The early use of disease modifying drugs has become widespread. James Fries, has demonstrated from the Aramis database, that the relative toxicity's of the disease modifying drugs, are similar overall to the nonsteroidal Anti-inflammatory drugs. Over 90 percent of Rheumatologists, now use combination therapy of multiple disease modifying drugs for rheumatoid arthritis. It has become apparent that using combination of these drugs does not increase their relative toxicity profiles.

It is realized that disease modifying drugs often lose their effectiveness, over time.

Many combinations exist:

methotrexate - hydroxychloroquine
methotrexate - Sulphasalazine
Sulphasalazine - hydroxychloroquine
methotrexate - hydroxychloroquine - Sulphasalazine.

The first major publicized study of triple therapy was that of O'Dell and co-workers, who looked at rheumatoid arthritis patients, who had failed single disease modifying antirheumatic drug (DMARD) therapy. O'Dell's findings suggested that the Sulphasalazine-hydroxychloroquine combination, was approximately the same as methotrexate alone in efficacy. However combination of Sulphasalazine-hydroxychloroquine-methotrexate, was statistically much better than in methotrexate alone or methotrexate-Sulphasalazine. Three years of triple therapy, 73 percent of patients showed at least 50 percent improvement. Ten percent had withdrawn because of side effects and 17 percent withdrew because of lack of efficacy. O'Dell found that an attempt to withdraw one of the three agents, resulted in a flare of the disease. He suggested that it was advisable to maintain all three drugs ongoing.

Few studies are available that, compare combination therapy with cyclosporin, but evidence suggests that combination therapy results are probably better than in cyclosporin alone.

No studies are available of combination of DMARD therapy with biological therapy such as Anti- TNF or soluble TNF Alpha receptor antibody.


O'Dell J.: Combination DMARD therapy rheumatoid arthritis: apparent universal acceptance. Arthritis Rheumatism 40 (supplement 9): 50, 1997

O'Dell J. et al.: treatment of rheumatoid arthritis with methotrexate alone, Sulphasalazine and hydroxychloroquine, or a combination of all three medications. New England Journal of Medicine 334: 1287-1291, 1996.

O'Dell J. et al.: methotrexate to Sulphasalazine hydroxychloroquine combination therapy in rheumatoid arthritis: continued efficacy with minimal toxicity at three years. Arthritis and Rheumatism 39 (supplement 9): 123, 1996.


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