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Randomized clinical trials of combinations of nonbiologic DMARDs in rheumatoid arthritis

James R O'Dell, MD
Section Editor
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Deputy Editor
Paul L Romain, MD


More than a dozen traditional disease-modifying antirheumatic drugs (DMARDs) and biologic agents, respectively termed nonbiologic and biologic DMARDs, are currently available; thus, there are more than 100 and 1000 potential combinations of two and three DMARDs, respectively. Of these, only a few have been directly compared in randomized clinical trials. Some well-designed studies have demonstrated clinically significant efficacy with a generally acceptable risk of toxicity.

Representative clinical trials of various combinations of nonbiologic DMARDs in early and established rheumatoid arthritis (RA) will be reviewed here. The general approach to management of RA and randomized controlled trials of biologic agents in this disease are discussed separately. (See "General principles of management of rheumatoid arthritis in adults" and "Randomized clinical trials of tumor necrosis factor inhibitors in rheumatoid arthritis" and "Rituximab and other B cell targeted therapies for rheumatoid arthritis" and "T-cell targeted therapies for rheumatoid arthritis" and "Randomized clinical trials in rheumatoid arthritis of biologic agents that inhibit IL-1, IL-6, and RANKL".)


Gold and MTX — The clinical effectiveness of the combination of intramuscular gold when added to ongoing methotrexate (MTX) was best illustrated in a study in which 65 patients with rheumatoid arthritis (RA) and a partial response to MTX (mean dose of 18.5 mg per week) continued MTX therapy and were randomly assigned to receive gold sodium thioglucose (initial dose of 10 mg, followed by 25 mg at week one and 50 mg per week thereafter) or placebo injections for 48 weeks [1]. At the end of the trial, those who received gold injections did significantly better than the placebo group:

American College of Rheumatology (ACR) 20 percent improvement (ACR20 responses) occurred in a significantly greater proportion of gold plus MTX-treated subjects (61 versus 30 percent).

ACR50 responses also occurred more often in those receiving gold (26 versus 4 percent).


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Literature review current through: Sep 2016. | This topic last updated: Jan 2, 2014.
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