[en] [en] 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.
Disciplines :
Rheumatology
Author, co-author :
Hannani, Monica T; Nordic Bioscience, Herlev, Denmark, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: mth@nordicbio.com
Thudium, Christian S; Nordic Bioscience, Herlev, Denmark. Electronic address: cst@nordicbio.com
Gellhorn, Alfred C; GlaxoSmithKline USA, Philadelphia, PA, USA. Electronic address: alfred.c.gellhorn@gsk.com
Larkin, Jonathan; Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland, SynOA Therapeutics, Philadelphia, PA, USA. Electronic address: jonathan.2.larkin@gmail.com
Ladel, Christoph ; CHL4special, Darmstadt, Germany. Electronic address: christoph.ladel@gmail.com
Struglics, André ; Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, Sweden. Electronic address: andre.struglics@med.lu.se
Uebelhoer, Melanie; Artialis SA, Liège, Belgium. Electronic address: melanie.uebelhoer@artialis.com
Henrotin, Yves ; Université de Liège - ULiège > Département des Sciences de l'activité physique et de la réadaptation > Pathologie générale et physiopathologie - Techniques particulières de kinésithérapie
Blanco, Francisco J; Instituto de Investigación Biomédica de A Coruña, Grupo de Investigación de Reumatología (GIR), Centro de Investigacion de Ciencias Avanzadas, Departamento de Fisioterapia, Medicina y Ciencias Biomedicas, Universidade da Coruña, Coruña, Spain. Electronic address: fblagar@sergas.es
Haugen, Ida K; Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway. Electronic address: ida.k.haugen@gmail.com
Kloppenburg, Margreet ; Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands, Department of Rheumatology, Zuyderland Medical Center, Heerlen, the Netherlands. Electronic address: g.kloppenburg@lumc.nl
Berenbaum, Francis ; Sorbonne University, INSERM CRSA, AP-HP Saint-Antoine Hospital, Paris, France. Electronic address: francis.berenbaum@aphp.fr
Mobasheri, Ali ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Bacardit, Jaume ; School of Computing, Newcastle University, Newcastle upon Tyne, United Kingdom. Electronic address: jaume.bacardit@newcastle.ac.uk
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