title: The efficacy and toxicity of combination therapy in rheumatoid arthritis. A meta-analysis.
abstract: OBJECTIVE
  To evaluate the efficacy and toxicity of combination therapy, compared with single second-line drug therapy, in rheumatoid arthritis.
  
  
  METHODS
  This study was a meta-analysis of published trials that evaluated combinations of full-dose second-line drugs and compared them with single second-line drugs at full dose. Using a random effects model, we summarized the difference between improvement with combination therapy and improvement with single-drug therapy.
  
  
  RESULTS
  Five trials that met inclusion criteria, which contained 749 entering patients and 516 completing patients, were identified. The mean +/- SEM difference in improvement in tender joint count between combination and single-drug therapy at end of trial (24-52 weeks) was 2.4 +/- 0.7 joints (out of 60) (P < 0.001). At end of trial the difference between therapies in swollen joint counts was 1.0 +/- 1.2 joints (P = 0.42). The difference in grip strength improvement was 3.7 +/- 4.3 mm Hg (P = 0.40), and 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 combination therapy-treated patients experienced side effect-related discontinuation of therapy than patients receiving single-drug therapy (P = 0.008).
  
  
  CONCLUSIONS
  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 combination therapy regimens are not recommended for widespread use. Other more aggressive regimens with additional drugs or higher drug doses than have been studied might be more efficacious, but with an even higher rate of toxicity.
authors.affiliation: Boston University Arthritis Center, Massachusetts 02118.
authors.forename: D T
authors.initials: DT
authors.lastname: Felson
authors.forename: J J
authors.initials: JJ
authors.lastname: Anderson
authors.forename: R F
authors.initials: RF
authors.lastname: Meenan
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D006801:Humans; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents