-308 A/G POLYMORPHISM IN THE TUMOR NECROSIS FACTOR-A GENE INFLUENCES OUTCOME OF ETANERCEPT TREATMENT IN RHEUMATOID ARTHRITIS

Background: 25% of RA patients do not respond well to TNF alpha inhibitors, and this might be influenced by -308 A/G polymorphism in the TNF alpha gene, as already observed in RA patients treated by infliximab (1).Objectives: Here, we tested whether - 308 A/G TNF alpha gene polymorphism can predict the outcome of etanercept treatment in 86 patients with Rheumatoid arthritis.Methods: 86 RA patients (69 women, 17 men, mean age 56,5±14.2 years) treated by etanercept alone (25mg biweekly) were genotyped for -308 A/G TNF alpha gene polymorphism by PCR and melting curve analysis with the Light Cycler (Roche Diagnostics) using specific gene primers and probes. Patients were subdivided into group A (G/A genotype) and group B (G/G genotype). We compared clinical responses to etanercept between groups A and B after 6 months, using the Disease Activity Score Index in 28 joints (DAS 28). 48 of these patients were also evaluated after 12 months.Results: 18 of the 86 patients (20,9%) belonged in group A and 68 of the 86 patients (79,1%) belonged in group B. There was no significant clinical or biological difference between patients from groups A and B at treatment onset. Methotrexate treatment was interrupted before starting etanercept therapy.After 6 month treatment, 10 of 18 patients in group A (55,6%) and 56 of 68 patients in group B (82,4%) had DAS 28 index improvement higher than 1.2 (Chi-Square, p=0.027). The average DAS28 improvement was 1.69±1.31 in group A and 2.23±1.19 in group B (t-test, p=0.098).10 patients from group A (20,8%) and 38 patients (79,1%) from group B were evaluated at 1 year. 4 of 10 patients in group A (40%) and 33 of 38 patients in group B (86,8%) had DAS 28 index improvement higher than 1.2 (Chi-Square, p=0.005). The average DAS28 improvement was 1.495±1.374 in group A and 2.318±1.357 in group B (U Mann-Whitney= 115; p=0,0057).Conclusion: RA patients with a - 308 G/G TNF alpha genotype respond better to etanercept than patients with - 308 A/G genotype.References: 1. Mugnier B, Balandraud N, Darque A, Roudier C, Roudier J, Reviron D. Polymorphism at position 308 of the tumor necrosis factor alpha gene influences outcome of infliximab therapy in rheumatoid arthritis. Arthritis and Rheumatism 48, 1849-1852, 2003.Citation: Ann Rheum Dis, volume 65, supplement II, year 2006, page 149Session: Rheumatic arthritis – prognosis and predictors