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Lookup NU author(s): Dr Federico Angelini, Dr Paweł Widera, Professor Jaume Bacardit
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© Objectives Osteoarthritis (OA) patient stratification is an important challenge to design tailored treatments and drive drug development. Biochemical markers reflecting joint tissue turnover were measured in the IMI-APPROACH cohort at baseline and analysed using a machine learning approach in order to study OA-dominant phenotypes driven by the endotype-related clusters and discover the driving features and their disease-context meaning. Method Data quality assessment was performed to design appropriate data preprocessing techniques. The k-means clustering algorithm was used to find dominant subgroups of patients based on the biochemical markers data. Classification models were trained to predict cluster membership, and Explainable AI techniques were used to interpret these to reveal the driving factors behind each cluster and identify phenotypes. Statistical analysis was performed to compare differences between clusters with respect to other markers in the IMI-APPROACH cohort and the longitudinal disease progression. Results Three dominant endotypes were found, associated with three phenotypes: C1) low tissue turnover (low repair and articular cartilage/subchondral bone turnover), C2) structural damage (high bone formation/resorption, cartilage degradation) and C3) systemic inflammation (joint tissue degradation, inflammation, cartilage degradation). The method achieved consistent results in the FNIH/OAI cohort. C1 had the highest proportion of non-progressors. C2 was mostly linked to longitudinal structural progression, and C3 was linked to sustained or progressive pain. Conclusions This work supports the existence of differential phenotypes in OA. The biomarker approach could potentially drive stratification for OA clinical trials and contribute to precision medicine strategies for OA progression in the future. Trial registration number NCT03883568.
Author(s): Angelini F, Widera P, Mobasheri A, Blair J, Struglics A, Uebelhoer M, Henrotin Y, Marijnissen ACA, Kloppenburg M, Blanco FJ, Haugen IK, Berenbaum F, Ladel C, Larkin J, Bay-Jensen AC, Bacardit J
Publication type: Article
Publication status: Published
Journal: Annals of the Rheumatic Diseases
Year: 2022
Volume: 81
Issue: 5
Pages: 666-675
Print publication date: 01/05/2022
Online publication date: 04/03/2022
Acceptance date: 01/02/2022
ISSN (print): 0003-4967
ISSN (electronic): 1468-2060
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/annrheumdis-2021-221763
DOI: 10.1136/annrheumdis-2021-221763
PubMed id: 35246457
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