TY - JOUR
T1 - Longitudinal stability of molecular endotypes of knee osteoarthritis patients
AU - Hannani, Monica T.
AU - Thudium, Christian S.
AU - Gellhorn, Alfred C.
AU - Larkin, Jonathan
AU - Karsdal, Morten A.
AU - Lisowska-Petersen, Zofia
AU - Frederiksen, Peder
AU - Bager, Cecilie L.
AU - Ladel, Christoph
AU - Struglics, André
AU - Uebelhoer, Melanie
AU - Henrotin, Yves
AU - Bihlet, Asger R.
AU - Blanco, Francisco J.
AU - Haugen, Ida K.
AU - Kloppenburg, Margreet
AU - Berenbaum, Francis
AU - Mobasheri, Ali
AU - Bacardit, Jaume
AU - Bay-Jensen, Anne Christine
PY - 2025/1
Y1 - 2025/1
N2 - 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.
AB - 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.
KW - Endotype
KW - Endotyping
KW - Knee osteoarthritis
KW - Longitudinal study
KW - Osteoarthritis
KW - Stratification
U2 - 10.1016/j.joca.2024.11.002
DO - 10.1016/j.joca.2024.11.002
M3 - Article
C2 - 39522936
AN - SCOPUS:85210539944
SN - 1063-4584
VL - 33
SP - 166
EP - 175
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
IS - 1
ER -