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TNF alpha –308 G>A polymorphism is not associated with response to TNF-alpha-blockers in Caucasian patients with rheumatoid arthritis: systematic review and meta-analysis.
  1. Stephan Pavy1,*,
  2. Eric J M Toonen2,
  3. Corinne Miceli-Richard1,
  4. Pilar Barrera3,
  5. Piet LCM van Riel3,
  6. Lindsey A Criswell4,
  7. Xavier Mariette5,
  8. Marieke Coenen2
  1. 1 Hopital Universitaire de Bicêtre, France;
  2. 2 Radboud University Nijmegen Medical Centre, Netherlands;
  3. 3 UMC Nijmegen, Netherlands;
  4. 4 University of California, San Francisco, United States;
  5. 5 Service de Rhumatologie, France
  1. Correspondence to: Stephan Pavy, Service de rhumatologie, Hopital Universitaire de Bicêtre, 78, rue du Général Leclerc, Le Kremlin Bicêtre, 94275, France; stephan.pavy{at}


Objective: There is a need for biomarkers that are able to predict anti-tumour necrosis factor (anti-TNF) treatment outcome in patients with rheumatoid arthritis (RA). Several studies have suggested that the rare A allele of the tumour necrosis factor alpha (TNFA) -308G>A polymorphism could be associated with a poorer response to anti-TNF therapy. Nevertheless, these results remain controversial. We performed a meta-analysis to determine whether the TNFA -308G>A polymorphism is associated with response to anti-TNF treatment in patients with RA .

Methods: A bibliographic search identified studies in which the TNFA –308G>A gene polymorphism was investigated in Caucasian RA patients treated with anti-TNF agents. Complementary data were requested when the DAS28 was not used as the primary outcome measure. Odds ratios (OR) for response based on DAS28 and standardized mean difference (SMD) for mean improvement of DAS28 were calculated to assess the potential association between TNFA -308 genotypes and response to anti-TNF agents.

Results: The bibliographic search yielded twelve studies that met the inclusion criteria. Those were supplemented with the data from a large Dutch cohort (n=426). The OR based on twelve studies including 1721 patients was 1.24 (95%CI 0.98-1.56) and the SMD based on eleven studies including 2576 patients was -0.15 (95%CI -0.38-+0.07). Sub-group analysis based on the two classes of anti-TNF agents did not demonstrate any association between TNFA -308 genotypes and anti-TNF treatment outcome.

Conclusion: According to this meta-analysis, the TNFA -308 polymorphism is not a predictor of the clinical response to anti-TNF treatment in RA.

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