Autoantibody biomarkers and first-line therapy response in RA: findings from the CAP48 cohort

Abstract

Objective A panel of antibodies against three antigens, University Hasselt (UH)-rheumatoid arthritis (RA).305, 318 and 329, has been associated with lack of response to first-line therapy in the Care in early RA trial. This study aimed to determine the association of this antibody panel with first-line therapy response in an independent cohort.Methods Anti-UH-RA.305/318/329 antibody reactivity was determined using ELISA in 165 baseline samples of the CAP48 cohort, an observational cohort of patients with early and na & iuml;ve RA treated mainly with methotrexate monotherapy. Multivariable analyses assessed associations between baseline antibody reactivity and failure to reach remission or low disease activity (LDA) at 3, 6, 9 and 24 months according to the Disease Activity Score 28-joint C-reactive protein (DAS28CRP) and clinical/simplified disease activity index (SDAI).Results In the total RA cohort, baseline anti-UH-RA.305/318/329 antibody reactivity was significantly higher in patients not achieving LDA versus those achieving LDA at 9 months (31.6% vs 11.3% for DAS28CRP/SDAI; OR 3.64, 95% CI 1.34 to 9.91, p=0.045). In patients with seronegative RA, a significant association between antibody reactivity and not achieving LDA based on DAS28CRP (42.1% vs 12.5%; OR 5.09, 95% CI 1.2 to 27.0, p=0.05) was already observed at 6 months. After 24 months, baseline antibody positivity remained significantly associated with not achieving LDA based on SDAI (OR 29.9, 95% CI 2.5 to 109.2, p=0.01) in patients with seronegative status.Discussion In the CAP48 cohort, the anti-UH-RA antibody panel was associated with a lack of response to first-line therapy for certain clinical measures, observed at 9 months in the total RA cohort and at 6 and 24 months in patients with seronegative status. The antibody panel should be further validated for its use in early personalised RA treatment.