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Longitudinal stability of molecular endotypes of knee osteoarthritis patients

Lookup NU author(s): Professor Jaume BacarditORCiD

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Abstract

© 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.

Publication metadata

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: 2025

Volume: 33

Issue: 1

Pages: 166-175

Print publication date: 01/01/2025

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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