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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 naïve 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.