Abstract
BackgroundTo evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept.MethodsWe enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients’ clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. ‘Power Doppler (PD) responder’ was defined as a patient whose Δtotal PD score over 6 months was greater than the median change.ResultsAbatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23–0.91, p = 0.043) was an independent predictor of PD responder status.ConclusionSerum levels of bone biomarkers may be useful for predicting RA patients’ therapeutic responses to abatacept.Trial registrationName of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort studyTrial registration number: UMIN000012524Date of registration: 12/9/2013URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657
Highlights
To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept
A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline was an independent predictor of Power Doppler (PD) responder status
We evaluated the effect of abatacept treatment on bone biomarkers and explored whether bone biomarkers are associated with the therapeutic response in RA patients treated with abatacept, using the KUDOS data
Summary
To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. Abatacept is a soluble fusion protein consisting of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and the Fc portion of immunoglobulin G1 [3]. It selectively modulates the CD80/CD86:CD28 costimulatory signal required for full T-cell activation [3]. Both clinical trials [4,5,6,7] and clinical practice [8] have demonstrated that abatacept is an effective treatment for patients with RA. CTLA-4 is suggested to be an anti-osteoclastogenic molecule that directly binds osteoclast precursor cells and inhibits their differentiation [10, 11]
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