Systematic review: comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis.
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.
Donahue
Katrina E
KE
University of North Carolina and Cecil G. Sheps Center for Health Services Research, Chapel Hill, North Carolina 27599, USA.
Gartlehner
Gerald
G
Jonas
Daniel E
DE
Lux
Linda J
LJ
Thieda
Patricia
P
Jonas
Beth L
BL
Hansen
Richard A
RA
Morgan
Laura C
LC
Lohr
Kathleen N
KN
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
D018501:Antirheumatic Agents; D001688:Biological Products