Background/Purpose: We have been prospectively investigating therapeutic efficacy of biologic or targeted synthetic DMARDs in patients with rheumatoid arthritis (RA) by ultrasound (US) in Kyushu region, Japan from June 2013. In this study, we have investigated efficacy of abatacept (ABT) by US indices and tried to find the correlations of those with serum cytokines, chemokines and bone-related biomarkers.

Methods: Forty-seven RA patients, registered and completed ABT therapy for 6 months, were enrolled from the Kyushu multicenter RA US prospective observational cohort study. They gave their informed consent to be subjected to the protocol that was approved by the Institutional Review Board of each center. We evaluated clinical disease activity, US synovitis score [22 joints including bilateral 1^st -5^th metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints and wrist joints semi-quantitatively examined by grey-scale (GS) and power Doppler (PD) from 0 to 3] and serum levels of 38 kinds of cytokine and chemokine biomarkers (multi-suspension array), bone-related biomarkers[TRACP-5b (EIA), sRANKL (ELISA), multi-suspension array; DKK-1, osteocalcin (OC), osteoprotegerin (OPG), osteopontin (OPN) and sclerostin (SOST)], rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (ACPA), matrix metalloproteinase-3 (MMP-3) at baseline, 3 and 6 months. Variables predicting PD non-responder defined that sum of PD score from 22 joints did not improve at 6 months were assessed.

Results: The median of disease duration was 82 months and that of DAS28-CRP was 4.49 at baseline. Clinical disease activity, US synovitis score, RF titer and MMP-3 significantly improved at 3 and 6 months from baseline (p<0.001). In addition, most of cytokines, chemokines and bone-related biomarkers were down- or up-regulated by ABT therapy. A multivariate logistic regression analysis revealed that longer disease duration (OR 1.01, 95%CI 1.01-1.03, p=0.0003), low PDUS syonovitis score (OR 0.75, 95%CI 0.54-0.92, p=0.0010) and high DKK-1 (OR 1.11, 95%CI 1.01-1.25, p=0.027) at baseline was predictive of PD non-responder (Table 1).

Conclusion: Cytokines, chemokines and bone-related biomarker differently changed after introduction of ABT therapy. Therapeutic response of ABT evaluated by US indices may be predicted by baseline bone-related biomarkers such as DKK-1.

Table 1. Multivariate regression analysis to predict power Doppler non-responder at 6 months

Variables with a p value less than 0.02 in univariate analysis were used in multivariate models.

CI, confidence interval; OR, odds ration