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Lookup NU author(s): Professor Jaume Bacardit
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Authors. Objective: To assess the longitudinal stability of biomarker-based molecular endotypes of knee osteoarthritis (KOA) participants from APPROACH and to evaluate the consistency of findings in an independent KOA population. Methods: Nineteen biomarkers were measured longitudinally in 295 KOA participants from the APPROACH cohort. K-means clustering was used to identify the structural damage, inflammation, and low tissue turnover endotypes at the six-, 12-, and 24-month follow-ups. Endotype stability was defined as having the same independent endotype assignment longitudinally for patients with complete data (n = 226). Clinical and biochemical characteristics were compared between participants with longitudinally stable and unstable endotypes. The presence and longitudinal stability of the endotypes were evaluated in a different KOA population from the placebo arm of the oral salmon calcitonin trials. Results: An average overall longitudinal endotype stability of 55% (Fleiss’ Kappa of 0.53; 95% confidence interval [CI]: 0.46, 0.60) was demonstrated. An average stability of 59% (range: 54–59%) was observed for the structural damage endotype (Fleiss’ Kappa 0.52; 95% CI: 0.45, 0.60), 54% (52–56%) for the inflammatory (Fleiss’ Kappa 0.61; 95% CI: 0.53, 0.68), and 50% (49–52%) for the low tissue turnover endotype (Fleiss’ Kappa 0.46; 95% CI: 0.39, 0.54). Participants with longitudinally unstable endotypes exhibited molecular properties of more than one endotype, which were detectable already at the first visit. Conclusions: Our study showed for the first time that more than half of KOA participants exhibited a longitudinally stable endotype, highlighting the applicability of biomarker-based endotyping in a clinical trial setting.
Author(s): Hannani MT, Thudium CS, Gellhorn AC, Larkin J, Karsdal MA, Lisowska-Petersen Z, Frederiksen P, Bager CL, Ladel C, Struglics A, Uebelhoer M, Henrotin Y, Bihlet AR, Blanco FJ, Haugen IK, Kloppenburg M, Berenbaum F, Mobasheri A, Bacardit J, Bay-Jensen A-C
Publication type: Article
Publication status: Published
Journal: Osteoarthritis and Cartilage
Year: 2024
Pages: Epub ahead of print
Online publication date: 08/11/2024
Acceptance date: 01/11/2024
Date deposited: 10/12/2024
ISSN (print): 1063-4584
ISSN (electronic): 1522-9653
Publisher: W.B. Saunders Ltd
URL: https://doi.org/10.1016/j.joca.2024.11.002
DOI: 10.1016/j.joca.2024.11.002
Data Access Statement: Data from APPROACH can be obtained upon reasonable request to the APPROACH Steering Committee.
PubMed id: 39522936
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