Burden of Disease and Drug Response for Patients with Rheumatoid Arthritis by Shared Epitope and Anti-Citrullinated Protein Antibody Status.

OBJECTIVE To characterize disease burden among adults with RA by both shared epitope (SE) and ACPA status, and to determine how their responses to abatacept, TNF inhibitors, and JAK inhibitors may differ. METHODS Utilizing data from two observational cohorts (FORWARD, VARA), individuals with RA were classified by SE/ACPA status. Outcomes included disease activity (PAS-II, RAPID3, DAS28), Rheumatic Disease Comorbidity Burden (RDCI), lifetime DMARD exposure, and healthcare utilization. Differences by SE/ACPA classification were determined with multiple linear regression. Response to DMARD initiation was assessed with linear regression for continuous measures of disease activity and logistic regression for achieving a change as large as the minimum clinically important difference. RESULTS A total of 3,243 individuals were included (FORWARD n=917, VARA n=2,326). Comorbidity burden among ACPA- individuals was higher than in ACPA+ in both cohorts (RDCI, SE+/ACPA+ vs SE-/ACPA-, B [95% CI]; FORWARD -0.35 [-0.65 to -0.05], p=0.02; VARA -0.35 [-0.63 to -0.08], p=0.01). In FORWARD there were significant differences in disease burden, including lower disease activity (PAS-II -0.77 [-1.10 to -0.44], p<0.001), lower healthcare utilization (rheumatology visits -0.18 [-0.35 to 0.0], p=0.046), and higher DMARD counts (0.43 [0.02 to 0.85], p=0.04) among SE+/ACPA+ individuals. ACPA+ abatacept initiators were more likely to experience clinically important improvements in PAS-II and DAS28, but RAPID3 was not significantly associated with abatacept response. CONCLUSION Our results highlight important differences in disease burden by SE/ACPA status and suggest that ACPA status, rather than correlative SE status, may be the stronger predictor of abatacept response among individuals with RA.