Based on the AMPLE study [19], and given the known association of ACPAs with HLA-DRB1 SE status [20], in the present study, we hypothesized that the presence of the SE might define a subset of patients with early, autoantibody-positive RA whose immunopathophysiology leads to enhanced clinical responses to treatment with a T-cell co-stimulatory modulator, such as abatacept, versus a TNF inhibitor, such as adalimumab. This evidence concerns the gene TNF and rheumatoid arthritis.