Abstract
OBJECTIVE: The effect of the shared epitope (SE) and valine at position 11 (Val11) of HLA-DRB1 on the activation of CD4(+) T cells is expected to be diminished by abatacept, a costimulation blocker. However, published evidence on the value of genetic stratification for abatacept treatment is conflicting. We aimed to compare the difference in effectiveness of abatacept and adalimumab in patients carrying the SE (or Val11). METHODS: The Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate is a nationwide observational cohort study recruiting patients from 53 centers across the United Kingdom before the initiation of biologic treatment and following them up prospectively for 12 months. Three hundred forty-two patients starting either abatacept or adalimumab were eligible for this analysis. Serum drug levels for abatacept, adalimumab, and methotrexate were determined at multiple time points. Multivariate modeling integrating demographic, clinical, and pharmacological variables was used to test for associations between the number of copies of the SE or Val11 and response to treatment (EULAR response; Disease Activity Score in 28 joints [DAS28] remission; change in DAS28). Differential effectiveness between drugs and genetic markers was assessed by the significance of their interaction term. RESULTS: There was no difference in the efficacy of abatacept versus adalimumab. We found weak evidence for an independent association of genetic markers with response to treatment (Val11 with EULAR response: P = 0.02), but there was no significant difference in this effect between drugs. CONCLUSION: We found no evidence that HLA typing is clinically useful to support prescription decisions for these two drugs.