Longitudinal stability of molecular endotypes of knee osteoarthritis patients

Hannani, Monica T.; Thudium, Christian S.; Gellhorn, Alfred C.; Larkin, Jonathan; Karsdal, Morten A.; Lisowska-Petersen, Zofia; Frederiksen, Peder; Bager, Cecilie L.; Ladel, Christoph; Struglics, André; Uebelhoer, Melanie; Henrotin, Yves; Bihlet, Asger R.; Blanco García, Francisco J; Haugen, Ida Kristin; Kloppenburg, Margreet; Berenbaum, Francis; Mobasheri, Ali; Bacardit, Jaume; Bay-Jensen, Anne C

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http://hdl.handle.net/2183/40570

Longitudinal stability of molecular endotypes of knee osteoarthritis patients

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Identifiers

URI: http://hdl.handle.net/2183/40570

DOI: 10.1016/j.joca.2024.11.002

Publication date

2024-11-08

Authors

Hannani, Monica T.

Thudium, Christian S.

Gellhorn, Alfred C.

Larkin, Jonathan

Karsdal, Morten A.

Lisowska-Petersen, Zofia

Frederiksen, Peder

Bager, Cecilie L.

Ladel, Christoph

Struglics, André

Bibliographic citation

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 AC. Longitudinal stability of molecular endotypes of knee osteoarthritis patients. Osteoarthritis Cartilage. 2025;33(1):166-175.

Abstract

[Abstract] 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.