title: The effectiveness of anti-TNF-alpha therapies when used sequentially in rheumatoid arthritis patients: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To systematically review and meta-analyse evidence on the effectiveness of the TNF-α inhibitors when used sequentially.
  
  
  METHODS
  Systematic review of comparative and single-arm observational studies. Data were synthesized using random-effects meta-analysis. Treatment effects were estimated using four outcome measures from the included studies: European League Against Rheumatism (EULAR) and ACR20 response rates and mean improvement in disease activity score-28 (DAS-20) and HAQ. The effect of other factors was explored via meta-regression and sub-group analyses.
  
  
  RESULTS
  Twenty studies comprising 2705 patients were included in the analysis. All studies were observational and most had no control group. Therefore, our primary analysis considered patient changes from baseline. The mean percentage of ACR20 responders was 60.8% (95% CI 53.8, 67.4), EULAR responders 70.5% (95% CI 63.7, 76.6), mean overall improvement in DAS-28 scores was 1.53 (95% CI 1.25, 1.80) and in HAQ scores was 0.25 (95% CI 0.11, 0.40). Four studies made comparisons with patients who received TNF-α inhibitors for the first time. Response rates associated with sequential TNF-α inhibitor treatment were lower than for first-time use.
  
  
  CONCLUSIONS
  Sequential TNF-α inhibitor use is likely to lead to treatment benefit in terms of the signs and symptoms of disease and physical function. There is also some evidence to suggest that the probability of achieving a response is lower, and the average magnitude of response is lower than the first use. Further evidence from randomized controlled trials is required to confirm and further quantify the role specific anti-TNF-α agents have when used sequentially.
authors.affiliation: Department of Health Sciences, University of Leicester, Leicester, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lloyd
authors.forename: Sylwia
authors.initials: S
authors.lastname: Bujkiewicz
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Wailoo
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Sutton
authors.forename: David
authors.initials: D
authors.lastname: Scott
mesh_terms: D000911:Antibodies, Monoclonal / Q000191:economics / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000191:economics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000191:economics; D017408:Guidelines as Topic; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013222:State Medicine / Q000191:economics; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000191:economics / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha