Lookup NU author(s): Dr Kate Potter,
Professor John Isaacs
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Anti-tumour necrosis factor (TNF) agents have revolutionised the treatment of patients with Rheumatoid Arthritis (RA). These therapies are however expensive and 30% of patients fail to respond. In a large cohort of Caucasian RA patients treated with anti-TNF medications (total n=1050, etanercept n=455, infliximab n=450) we investigated whether genotypes of eight single nucleotide polymorphisms (SNPs) in the region containing the TNF gene were associated with response to anti-TNF therapy. Linear regression analyses adjusted for baseline 28 joint disease activity score (DAS28), baseline health assessment questionnaire (HAQ) score, gender and concurrent disease modifying anti-rheumatic drug (DMARD) treatment, were used to assess association of these polymorphisms with treatment response, defined by change in DAS28 after 6 months. Analyses were performed in the entire cohort, and also stratified by anti-TNF agent. Association between DAS28 response and TNF-308 (rs1800629) genotype (p=0.001) was detected across the whole cohort. After stratification by anti-TNF agent, the rare TNF-308AA genotype was associated with a significantly poorer response compared with TNF-308GG in etanercept (p=0.001, n=7) but not infliximab (p=0.8, n=17) treated patients. Conversely, the GA genotype at TNF-238 (rs361525) was associated with a poorer response to infliximab (p=0.028 n=40), but not etanercept (p=0.6 n=33). Due to the small numbers of patients in some of the genotype groups examined, our data must be regarded as preliminary and will require replication in further large cohorts of anti-TNF treated patients. If confirmed our findings suggest the potential for genotype at these markers to aid selection of anti-TNF agent in patients with RA.
Author(s): Maxwell JR, Potter C, Hyrich KL, Barton A, Worthington J, Isaacs JD, Morgan AW, Wilson AG
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
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