title: Systematic review: comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis.
abstract: BACKGROUND
  The comparative effectiveness of rheumatoid arthritis therapies is uncertain.
  
  
  OBJECTIVE
  To compare the benefits and harms of disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis.
  
  
  METHODS
  Records limited to the English language and studies of adults were identified by using MEDLINE, EMBASE, The Cochrane Library, and International Pharmaceutical Abstracts from 1980 to September 2007.
  
  
  METHODS
  Two persons independently selected relevant head-to-head trials and prospective cohort studies with at least 100 participants and 12-week follow-up and relevant good- or fair-quality meta-analyses that compared benefits or harms of 11 drug therapies. For harms, they included retrospective cohort studies.
  
  
  METHODS
  Information on study design, interventions, outcomes, and quality were extracted according to a standard protocol.
  
  
  RESULTS
  Head-to-head trials (n = 23), mostly examining synthetic DMARDs, showed no clinically important differences in efficacy among synthetic DMARDs (limited to methotrexate, leflunomide, and sulfasalazine) or among anti-tumor necrosis factor drugs (adalimumab, etanercept, and infliximab). Monotherapy with anti-tumor necrosis factor drugs resulted in better radiographic outcomes than did methotrexate but no important differences in clinical outcomes (for example, 20%, 50%, or 70% improvement according to American College of Rheumatology response criteria). Various combinations of biological DMARDs plus methotrexate improved clinical response rates and functional outcomes more than monotherapy with either methotrexate or biological DMARDs. In patients whose monotherapy failed, combination therapy with synthetic DMARDs improved response rates. Numbers and types of short-term adverse events were similar for biological and synthetic DMARDs. The evidence was insufficient to draw conclusions about differences for rare but serious adverse events for biological DMARDs.
  
  
  CONCLUSIONS
  Most studies were short-term efficacy trials conducted in selected populations with few comorbid conditions.
  
  
  CONCLUSIONS
  Limited available comparative evidence does not support one monotherapy over another for adults with rheumatoid arthritis. Although combination therapy is more effective for patients whose monotherapy fails, the evidence is insufficient to draw firm conclusions about whether one combination or treatment strategy is better than another or is the best treatment for early rheumatoid arthritis.
authors.affiliation: University of North Carolina and Cecil G. Sheps Center for Health Services Research, Chapel Hill, North Carolina 27599, USA.
authors.forename: Katrina E
authors.initials: KE
authors.lastname: Donahue
authors.forename: Gerald
authors.initials: G
authors.lastname: Gartlehner
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Jonas
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Lux
authors.forename: Patricia
authors.initials: P
authors.lastname: Thieda
authors.forename: Beth L
authors.initials: BL
authors.lastname: Jonas
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hansen
authors.forename: Laura C
authors.initials: LC
authors.lastname: Morgan
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Lohr
mesh_terms: D000328:Adult; D000367:Age Factors; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products