@article{oai:nagasaki-u.repo.nii.ac.jp:00026822,
 author = {Kawashiri, Shin-ya and Endo, Yushiro and Nishino, Ayako and Okamoto, Momoko and Tsuji, Sosuke and Takatani, Ayuko and Shimizu, Toshimasa and Sumiyoshi, Remi and Koga, Tomohiro and Iwamoto, Naoki and Ichinose, Kunihiro and Tamai, Mami and Nakamura, Hideki and Origuchi, Tomoki and Aramaki, Toshiyuki and Ueki, Yukitaka and Yoshitama, Tamami and Eiraku, Nobutaka and Matsuoka, Naoki and Okada, Akitomo and Fujikawa, Keita and Hamada, Hiroaki and Nagano, Shuji and Tada, Yoshifumi and Kawakami, Atsushi},
 journal = {BMC Musculoskeletal Disorders},
 month = {Jun},
 note = {Background: 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.
Methods: We 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.
Results: Abatacept 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.
Conclusion: Serum levels of bone biomarkers may be useful for predicting RA patients’ therapeutic responses to abatacept.
Trial registration: Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study
Trial registration number: UMIN000012524
Date of registration: 12/9/2013
URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657, BMC Musculoskeletal Disorders, 22, art. no. 506; 2021},
 title = {Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan},
 volume = {22},
 year = {2021}
}