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

• Published in: BMC musculoskeletal disorders 2021-06, Vol.22 (1), p.1-506, Article 506
• Main Authors: Kawashiri, Shin-ya, Endo, Yushiro, Nishino, Ayako, Okamoto, Momoko, Tsuji, Sosuke, Takatani, Ayuko, Shimizu, Toshimasa, Sumiyoshi, Remi, Koga, Tomohiro, Iwamoto, Naoki, Ichinose, Kunihiro, Tamai, Mami, Nakamura, Hideki, Origuchi, Tomoki, Aramaki, Toshiyuki, Ueki, Yukitaka, Yoshitama, Tamami, Eiraku, Nobutaka, Matsuoka, Naoki, Okada, Akitomo, Fujikawa, Keita, Hamada, Hiroaki, Nagano, Shuji, Tada, Yoshifumi, Kawakami, Atsushi
• Format: Article
• Language: English
• Subjects: Abatacept; Biological markers; Biomarkers; Bisphosphonates; Clinical trials; Cohort analysis; Dickkopf-1; Disease; Dkk1 protein; Drug therapy; Glycoproteins; Health aspects; Immunoassay; Joint diseases; Measurement; Musculoskeletal diseases; Musculoskeletal ultrasound; Nonsteroidal anti-inflammatory drugs; Osteocalcin; Osteopontin; Osteoprotegerin; Patients; Power Doppler; Prognosis; Protein hormones; Proteins; Rheumatoid arthritis; Rheumatology; Serum levels; SOST protein; TNF inhibitors; Tumor necrosis factor-TNF; Ultrasonic imaging; Ultrasound
• ISSN: 1471-2474; 1471-2474
• DOI: 10.1186/s12891-021-04392-5

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 [DELA] value. 'Power Doppler (PD) responder' was defined as a patient whose [DELA]total 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 [DELA]SOST and [DELA]OPG 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: Keywords: Rheumatoid arthritis, Musculoskeletal ultrasound, Abatacept, Dickkopf-1, Osteoprotegerin, Power Doppler, Sclerostin