Association between serum bone biomarker levels and ultrasonographic response in abatacept-treated rheumatoid arthritis patients

Abstract

Background To evaluate the effect of treatment on bone biomarkers and explore whether bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. Methods We enrolled 59 RA patients treated with abatacept from a multicenter prospective 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. Results Abatacept significantly improved clinical disease activity as well as the MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the introduction of abatacept (p = 0.016). The ΔSOST and ΔOPG values were negatively correlated with the Δtotal PD score (rs = − 0.31, p < 0.05 and rs = − 0.34, p < 0.01, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) compared to 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, p = 0.043) was an independent predictor of PD responder status. Conclusion Serum levels of bone biomarkers may be useful for predicting RA patients' ultrasonographic response to abatacept.

Toward Overcoming Treatment Failure in Rheumatoid Arthritis

“…Reduced type I IFN score, and higher expression of dendritic cells-related genes ( Basic Leucine Zipper ATF-Like Transcription Factor 2 (BATF) , Lysosomal Associated Membrane Protein 3 (LAMP-3) , CD83 , C-type Lectin Domain Family 4 Member A (CLEC4A) , Indoleamine 2, 3-dioxygenase 1 (IDO) , interferon regulatory factor (IRF)7 , STAT1 , STAT2 and TNF Superfamily Member 10 (TNFSF10) ) could be used as biomarkers to predict good response to abatacept ( 274 ). Increased dickkopf (Dkk)-1 serum level and sclerostin might indicate a poor prognosis and resistance to abatacept treatment in RA patients ( 275 ). Increased cartilage oligomeric matrix protein level served as a strong predictive biomarker for inadequate response to abatacept treatment for RA patients with a first TNF inhibitor failure ( 276 ) ( Table 3 ).…”