Tumour necrosis factor α −308G→A polymorphism is not associated with response to TNFα blockers in Caucasian patients with rheumatoid arthritis: systematic review and meta-analysis
- 4 December 2009
- journal article
- research article
- Published by BMJ in Annals Of The Rheumatic Diseases
- Vol. 69 (6), 1022-1028
- https://doi.org/10.1136/ard.2009.117622
Abstract
Background There is a need for biomarkers that can 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 α (TNFA) −308G→A polymorphism could be associated with a poorer response to anti-TNF therapy. Nevertheless, these results remain controversial. Objective To determine by a meta-analysis 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 patients with RA treated with anti-TNF agents. Complementary data were requested when the 28-joint count Disease Activity Score (DAS28) was not used as the primary outcome measure. Odds ratios (ORs) for response based on DAS28 and standardised 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 12 studies that met the inclusion criteria, which were supplemented with the data from a large Dutch cohort (n=426). The OR based on the 12 studies including 1721 patients was 1.24 (95% CI 0.98 to 1.56) and the SMD based on 11 studies including 2579 patients was −0.18 (95% CI −0.36 to 0.1). Subgroup 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.Keywords
This publication has 31 references indexed in Scilit:
- The exact distribution of Cochran's heterogeneity statistic in one‐way random effects meta‐analysisStatistics in Medicine, 2008
- A single tumour necrosis factor haplotype influences the response to adalimumab in rheumatoid arthritisAnnals Of The Rheumatic Diseases, 2007
- IL1 and TNF gene polymorphisms in patients with juvenile idiopathic arthritis treated with TNF inhibitorsAnnals Of The Rheumatic Diseases, 2007
- The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis populationAnnals Of The Rheumatic Diseases, 2006
- The influence of a polymorphism at position -857 of the tumour necrosis factor gene on clinical response to etanercept therapy in rheumatoid arthritisRheumatology, 2005
- The influence of genetic variation in the HLA–DRB1 and LTA–TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanerceptArthritis & Rheumatism, 2004
- Investigation of the Prognostic Value of TNF-α Gene Polymorphism among Patients Treated with Infliximab, and the Effects of Infliximab Therapy on TNF-α Production and ApoptosisPathobiology, 2004
- Influence of TNFα gene polymorphisms on TNFα production and diseaseHuman Immunology, 2001
- American college of rheumatology preliminary definition of improvement in rheumatoid arthritisArthritis & Rheumatism, 1995
- Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritisArthritis & Rheumatism, 1995