Antimalarial agents compared with or in combination with other disease-modifying antirheumatic drugs

Available published comparisons of antimalarial drugs with other disease-modifying antirheumatic drugs (DMARDs) are reviewed, as well as reports of combinations of DMARDs, in the treatment of rheumatoid arthritis and juvenile rheumatoid arthritis. These reports suggest that antimalarial drug toxicity is less than that of parenteral gold, D-penicillamine, auranofin, or dapsone. Its efficacy appears to be equal to or slightly less than that of most comparison DMARDs. Combinations of DMARDs with antimalarials are probably used by a substantial proportion of rheumatologists, but the few prospective, double-blind studies with a balanced design show little or no advantage to combination DMARD therapy. Open, nonrandomized studies and preliminary reports suggest that combination therapy may be useful, usually when another DMARD is added to one or more DMARDs to which the patients did not have a satisfactory response. A few large, prospective, double-blind, randomized studies comparing hydroxychloroquine with several other DMARDs and placebo are needed to establish more confidence in the relative efficacy and utility of hydroxychloroquine. Although the rationale for combination DMARD therapy is attractive, additional preliminary studies of the various possible combinations and doses are needed before definitive trials of promising combinations can be justified.