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, Francisco J; Haugen, Ida K; Kloppenburg, Margreet; Berenbaum, Francis; Mobasheri, Ali; Bacardit, Jaume; Bay-Jensen, Anne-Christine (2024-11-08)
Elsevier
08.11.2024
Hannani, M. T., Thudium, C. S., Gellhorn, A. C., Larkin, J., Karsdal, M. A., Lisowska-Petersen, Z., Frederiksen, P., Bager, C. L., Ladel, C., Struglics, A., Uebelhoer, M., Henrotin, Y., Bihlet, A. R., Blanco, F. J., Haugen, I. K., Kloppenburg, M., Berenbaum, F., Mobasheri, A., Bacardit, J., & Bay-Jensen, A.-C. (2025). Longitudinal stability of molecular endotypes of knee osteoarthritis patients. Osteoarthritis and Cartilage, 33(1), 166–175. https://doi.org/10.1016/j.joca.2024.11.002
https://creativecommons.org/licenses/by/4.0/
© 2024 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
© 2024 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202411296966
https://urn.fi/URN:NBN:fi:oulu-202411296966
Tiivistelmä
Summary
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.
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.
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