TY - JOUR
T1 - Poor correlation between biomarkers and MRI-detected joint damage in a cross-sectional study of persons with nonsevere hemophilia A (DYNAMO study)
AU - Kloosterman, Fabienne R.
AU - Zwagemaker, Anne-Fleur
AU - Bay-Jensen, Anne C.
AU - Cnossen, Marjon H.
AU - Kruip, Marieke J. H. A.
AU - Leebeek, Frank W. G.
AU - Hemke, Robert
AU - Maas, Mario
AU - Fijnvandraat, Karin
AU - Gouw, Samantha C.
AU - Coppens, Michiel
N1 - Funding Information: The authors thank Sandra van den Berg and Rachel van Luijk (Amsterdam UMC, Amsterdam, the Netherlands) for their technical support and help in conducting the MRI scans. The authors would like to thank Mia Mortensen of the Nordic Bioscience for her technical support. F.K. analyzed the data. F.K. and M.C. drafted the manuscript. F.K. and A.Z. collected, cleaned, and interpreted the data. K.F. designed the study. R.H. and M.M. designed the MRI scanning protocol and scored the MR images. M.H.C. F.W.G.L. M.K. S.C.G. M.C. and K.F. collected data or supervised data collection. A.C.B.J. performed and supervised the biomarker analyses. All authors reviewed this work and approved the final version of the manuscript. F.K. A.Z. R.H. and M.M. have no potential conflicts of interest. S.C.G. has received an unrestricted research grant from Sobi. M.H.C. has received investigator-initiated research and travel grants as well as speaker fees over the years from the Netherlands Organisation for Scientific Research (NWO), the Netherlands Organisation for Health Research and Development (ZonMw), the Dutch “Innovatiefonds Zorgverzekeraars,” Baxter/Baxalta/Shire/ Takeda, Pfizer, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, and Nordic Pharma and has served as a steering board member for Roche, Bayer, and Novartis. All grants, awards, and fees go to the Erasmus M.C. and M.J.H.A.K. has received unrestricted research grants from Sobi her institution received speakers fees from Sobi, Roche, and BMS. F.W.G.L. received unrestricted research grants from CSL Behring, Takeda, SOBI, and UniQure. He is a consultant for CSL Behring, Takeda, Biomarin, and UniQure, of which the fees go to the University. He was a DSMB member of a study sponsored by Roche. K.F. has received unrestricted research grants from Sobi, Pfizer, CSL Behring, and Novo Nordisk and her institution received consultancy fees from Grifols, Takeda, Novo Nordisk, and Roche. M.C. reports research funding from Bayer, CSL Behring, Daiichi Sankyo, Novo Nordisk, Alexion, Roche, and UniQure, and consultancy or lecturing fees from Bayer, CSL Behring, Novo Nordisk, and Sobi. Publisher Copyright: © 2023
PY - 2023/7
Y1 - 2023/7
N2 - Background: Persons with nonsevere hemophilia A (NSHA) experience less frequent joint bleeding than persons with severe hemophilia A, but may still develop joint damage. Biomarkers of cartilage and synovial remodeling can reflect ongoing pathologic processes that may precede or coincide with damage on joint imaging. If so, biomarkers may be an important diagnostic tool for joint damage in NSHA. Objective: To assess the correlation between biomarkers and MRI-detected joint damage in persons with NSHA. Methods: In a cross-sectional study, men with NSHA (factor VIII [FVIII], 2-35 IU/dL) were included. Participants underwent magnetic resonance imaging of elbows, knees, and ankles and blood and urine sampling for biomarker analysis on a single visit. The following biomarker(s) were analyzed in urine: CTX-II or serum: cartilage oligomeric matrix protein, chondroitin sulfate 846, vascular cell adhesion molecule 1, osteopontin (OPN), neo-epitope of MMP -mediated degradation of type II collagen, N-terminal propeptide of type II collagen, collagen type IV M, and propetide of type IV collagen. Spearman's rank correlations were calculated between these biomarkers and the total International Prophylaxis Study group (IPSG) score, soft-tissue subscore, and osteochondral subscore. Results: In total, 48 persons with NSHA were included. Median age was 43 years (range, 24-55 years) and median FVIII was 10 IU/dL (IQR, 4-16 IU/dL). The median IPSG score was 4 (IQR, 2-9). Median IPSG soft-tissue subscores were 3 (IQR, 2-4) and osteochondral subscores were 0 (IQR, 0-4). No strong correlations were found between the studied biomarkers, total IPSG score, subsequent soft-tissue, and osteochondral subscores. Conclusions: In this study, selected biomarkers indicative of different aspects of hemophilic arthropathy showed no consistent correlation with IPSG scores. This suggests that systemically measured biomarkers are currently not suitable for identifying milder joint damage in NSHA, as observed on magnetic resonance imaging.
AB - Background: Persons with nonsevere hemophilia A (NSHA) experience less frequent joint bleeding than persons with severe hemophilia A, but may still develop joint damage. Biomarkers of cartilage and synovial remodeling can reflect ongoing pathologic processes that may precede or coincide with damage on joint imaging. If so, biomarkers may be an important diagnostic tool for joint damage in NSHA. Objective: To assess the correlation between biomarkers and MRI-detected joint damage in persons with NSHA. Methods: In a cross-sectional study, men with NSHA (factor VIII [FVIII], 2-35 IU/dL) were included. Participants underwent magnetic resonance imaging of elbows, knees, and ankles and blood and urine sampling for biomarker analysis on a single visit. The following biomarker(s) were analyzed in urine: CTX-II or serum: cartilage oligomeric matrix protein, chondroitin sulfate 846, vascular cell adhesion molecule 1, osteopontin (OPN), neo-epitope of MMP -mediated degradation of type II collagen, N-terminal propeptide of type II collagen, collagen type IV M, and propetide of type IV collagen. Spearman's rank correlations were calculated between these biomarkers and the total International Prophylaxis Study group (IPSG) score, soft-tissue subscore, and osteochondral subscore. Results: In total, 48 persons with NSHA were included. Median age was 43 years (range, 24-55 years) and median FVIII was 10 IU/dL (IQR, 4-16 IU/dL). The median IPSG score was 4 (IQR, 2-9). Median IPSG soft-tissue subscores were 3 (IQR, 2-4) and osteochondral subscores were 0 (IQR, 0-4). No strong correlations were found between the studied biomarkers, total IPSG score, subsequent soft-tissue, and osteochondral subscores. Conclusions: In this study, selected biomarkers indicative of different aspects of hemophilic arthropathy showed no consistent correlation with IPSG scores. This suggests that systemically measured biomarkers are currently not suitable for identifying milder joint damage in NSHA, as observed on magnetic resonance imaging.
KW - biomarkers
KW - hemophilia A
KW - joint diseases
KW - joints
KW - magnetic resonance imaging
UR - http://www.scopus.com/inward/record.url?scp=85153611797&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jtha.2023.03.030
DO - https://doi.org/10.1016/j.jtha.2023.03.030
M3 - Article
C2 - 37019364
SN - 1538-7933
VL - 21
SP - 1813
EP - 1823
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 7
ER -