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.

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.