Clinical relevance of switching to a second tumour necrosis factor-alpha inhibitor after discontinuation of a first tumour necrosis factor-alpha inhibitor in rheumatoid arthritis: a systematic literature review and meta-analysis

Clin Exp Rheumatol. 2011 Jan-Feb;29(1):96-103. Epub 2011 Feb 23.


Objectives: To assess the clinical relevance of switching to a second tumour necrosis factor (TNF) alpha inhibitor after discontinuation of a first TNF-alpha inhibitor in patients with rheumatoid arthritis.

Methods: A systematic literature search of MEDLINE, EMBASE and Cochrane database and Congress abstracts up to March 2009 retrieved all studies assessing the efficacy of switching to a second TNF-alpha inhibitor. Key words were rheumatoid arthritis AND failure OR switching AND TNF-alpha inhibitors OR adalimumab OR etanercept OR infliximab. Efficacy was evaluated by American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) response criteria and drug survival. A meta-analysis of the percentage of responders was carried out. Statistical heterogeneity was tested by the Q-test.

Results: In the 32 relevant studies (4,441 patients) selected, the pooled percentage of ACR 20 responders (12 studies; 1,570 patients) was 55.1% (95% confidence interval, CI 48.2-62) and that of EULAR responders (15 studies; 2,665 patients) was 74.9% (95% CI 72.3-77.5). In the 19 studies analysing the efficacy by the reason to switch, the pooled percentage of ACR20 responders was 54.3% (95% CI 45.8-62.5) for switch because of lack of efficacy and 62.5% (95% CI 57.3-67.6) because of adverse events. The percentage of EULAR response was similar in both groups.

Conclusions: This meta-analysis suggests that switching to a second TNF-alpha inhibitor is clinically relevant in RA. Response to a second TNF-alpha inhibitor appears to be slightly better if the first TNF-alpha inhibitor was discontinued because of adverse events.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Databases, Bibliographic
  • Drug Substitution*
  • Health Status
  • Humans
  • Severity of Illness Index
  • Treatment Failure
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha