THE EFFICACY AND TOXICITY OF COMBINATION THERAPY IN RHEUMATOID-ARTHRITIS - A METAANALYSIS

Objective. To evaluate the efficacy and toxicity of combination therap y, compared with single second-line drug therapy, in rheumatoid arthri tis. Methods. This study was a meta-analysis of published trials that evaluated combinations of full-dose second-line drugs and compared the m with single second-line drugs at full dose. Using a random effects m odel, we summarized the difference between improvement with combinatio n therapy and improvement with single-drug therapy. Results. Five tria ls that met inclusion criteria, which contained 749 entering patients and 516 completing patients, were identified. The mean +/- SEM differe nce in improvement in tender joint count between combination and singl e-drug therapy at end of trial (24-52 weeks) was 2.4 +/- 0.7 joints (o ut of 60) (P < 0.001). At end of trial the difference between therapie s in swollen joint counts was 1.0 +/- 1.2 joints (P = 0.42). The diffe rence in grip strength improvement was 3.7 +/- 4.3 mm Hg (P = 0.40), a nd for erythrocyte sedimentation rate it was 3.4 +/- 3.1 mm/hour (P = 0.27). In general, the differences in efficacy between combination and single-drug therapy were clinically marginal. Nine percent more combi nation therapy-treated patients experienced side effect-related discon tinuation of therapy than patients receiving single-drug therapy (P = 0.008). Conclusion. Combination therapy, as it has been used in recent clinical trials, does not offer a substantial improvement in efficacy , but does have higher toxicity than single drug therapy. These combin ation therapy regimens are not recommended for widespread use. Other m ore aggressive regimens with additional drugs or higher drug doses tha n have been studied might be more efficacious, but with an even higher rate of toxicity.