How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort

M P Jansen¹, S C Mastbergen¹, W Wirth^{2

3}, F W Roemer^{4

5}, J Bacardit⁶, A C Bay-Jensen⁷, M Kloppenburg^{8

9}, F J Blanco¹⁰, I K Haugen¹¹, F Berenbaum^{12

13}, N Eijkelkamp¹⁴, M Jarraya¹⁵

Affiliations

¹ Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
² Research Program for Musculoskeletal Imaging, Center for Anatomy and Cell Biology & Ludwig Boltzmann Institute for Arthritis and Rehabilitation (LBIAR), Paracelsus Medical University, Salzburg, Austria.
³ Chondrometrics GmbH, Freilassing, Germany.
⁴ Quantitative Imaging Center, Department of Radiology, Boston University School of Medicine, Boston, MA, USA.
⁵ Department of Radiology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
⁶ Interdisciplinary Computing and Complex BioSystems (ICOS) Research Group, School of Computing, Newcastle University, Newcastle upon Tyne, United Kingdom.
⁷ ImmunoScience, Nordic Bioscience, Herlev, Denmark.
⁸ Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.
⁹ Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
¹⁰ Grupo de Investigación de Reumatología (GIR), INIBIC - Complejo Hospitalario Universitario de A Coruña, SERGAS, Centro de Investigación CICA, Departamento de Fisioterapia y Medicina, Universidad de A Coruña, A Coruña, Spain.
¹¹ Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway.
¹² Department of Rheumatology, AP-HP Saint-Antoine Hospital, Paris, France.
¹³ Sorbonne University, INSERM CRSA, Paris, France.
¹⁴ Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
¹⁵ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

PMID: 41531867
PMCID: PMC12794487
DOI: 10.1016/j.ocarto.2025.100726

How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort

M P Jansen et al. Osteoarthr Cartil Open. 2025.

. 2025 Dec 11;8(1):100726.

doi: 10.1016/j.ocarto.2025.100726. eCollection 2026 Mar.

Authors

Affiliations

¹ Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
² Research Program for Musculoskeletal Imaging, Center for Anatomy and Cell Biology & Ludwig Boltzmann Institute for Arthritis and Rehabilitation (LBIAR), Paracelsus Medical University, Salzburg, Austria.
³ Chondrometrics GmbH, Freilassing, Germany.
⁴ Quantitative Imaging Center, Department of Radiology, Boston University School of Medicine, Boston, MA, USA.
⁵ Department of Radiology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
⁶ Interdisciplinary Computing and Complex BioSystems (ICOS) Research Group, School of Computing, Newcastle University, Newcastle upon Tyne, United Kingdom.
⁷ ImmunoScience, Nordic Bioscience, Herlev, Denmark.
⁸ Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.
⁹ Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
¹⁰ Grupo de Investigación de Reumatología (GIR), INIBIC - Complejo Hospitalario Universitario de A Coruña, SERGAS, Centro de Investigación CICA, Departamento de Fisioterapia y Medicina, Universidad de A Coruña, A Coruña, Spain.
¹¹ Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway.
¹² Department of Rheumatology, AP-HP Saint-Antoine Hospital, Paris, France.
¹³ Sorbonne University, INSERM CRSA, Paris, France.
¹⁴ Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
¹⁵ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

PMID: 41531867
PMCID: PMC12794487
DOI: 10.1016/j.ocarto.2025.100726

Abstract

Objective: To explore associations between patient-reported pain outcomes and knee osteoarthritis (OA) subtypes based on systemic biochemical markers and joint structural pathology as defined by MRI.

Methods: Data were obtained from 297 knee OA patients from the IMI-APPROACH study. Pain outcomes were assessed using the KOOS, WOMAC, ICOAP, NRS, PainDETECT, and a pain diary. Biochemical markers in serum and urine were used to classify patients into systemic biomarker subtypes (low tissue turnover, structural damage, and systemic inflammation) via k-means clustering. Structural pathology subtypes were determined using MRI into an inflammatory, meniscus/cartilage damage, and subchondral bone pathology subtype. Associations between pain measures and subtypes were analyzed using multivariable regression models adjusted for age, sex, and BMI.

Results: The systemic inflammation biomarker subtype was significantly associated with higher KOOS pain, WOMAC weight-bearing pain, NRS knee pain, and PainDETECT scores (all p ≤ 0.042 and β ≥ 0.12). The low tissue turnover subtype negatively associated with lower KOOS, WOMAC, and ICOAP constant pain (all p ≤ 0.22 and β ≤ -0.13), and the structural damage subtype with lower PainDETECT scores (more nociceptive-like pain; p = 0.046 and β = -0.12). Among MRI subtypes, meniscus/cartilage damage was significantly associated with lower PainDETECT scores (p = 0.005 and β = -0.16). No significant associations were found for the subchondral bone subtype or pain diary outcomes.

Conclusion: For commonly used pain questionnaires, pain severity seems linked with inflammatory activity more than structural damage. Structural damage is primarily associated with nociceptive-like pain according to PainDETECT, which might be valuable for patient selection to clinical trials and observational studies.

Keywords: Biomarkers; Imaging; Neuropathic; Pain; Phenotyping.

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Conflict of interest statement

WW: Employee and shareholder of Chondrometrics GmbH. FWR: Shareholder of Boston Imaging Core Lab, LLC and consultant to Grünenthal GmbH. Editor in Chief Osteoarthritis Imaging. MK: Consulting fees from Pfizer, CHDR, Novartis, UCB, GSK, and Peptinov, all paid to institution. Royalties from Wolters-Kluwer and Springer Verlag, all paid to institution. FJB: Funding from Gedeon Richter Plc., Bristol-Myers Squibb International Corporation, Sun Pharma Global FZE, Celgene Corporation, Janssen Cilag International N.V, Janssen Research & Development, Viela Bio, Inc., Astrazeneca AB, UCB BIOSCIENCES GMBH, UCB BIOPHARMA SPRL, AbbVie Deutschland GmbH & Co.KG, Merck KGaA, Amgen, Inc., Novartis Farmacéutica, S.A., Boehringer Ingelheim España, S.A, CSL Behring, LLC, Glaxosmithkline Research & Development Limited, Pfizer Inc, Lilly S.A., Corbus Pharmaceuticals Inc., Biohope Scientific Solutions for Human Health S.L., Centrexion Therapeutics Corp., Sanofi, TEDEC-MEIJI FARMA S.A., KiniksaPharmaceuticals, Ltd. Grunenthal. IKH: Research grant (ADVANCE) from Pfizer (payment to institution) and personal fees from Abbvie, Novartis, Grünenthal and GSK, outside of the submitted work. FB: consulting fees from Grunenthal, GSK, Eli Lilly, Novartis, Pfizer, Servier, and 4P Pharma; honoraria from Viatris, Pfizer, and Zoetis; travel support from Nordic Pharma; holds patents related to 4Moving Biotech; serves on advisory boards for AstraZeneca, Sun Pharma, and Nordic Bioscience; and holds stock in 4P Pharma and 4Moving Biotech. CMO and co-founder of 4Moving Biotech. The other authors report no conflict of interest.

References

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How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort

Affiliations

How are patient-reported pain outcomes associated with biomarker and structural pathology subtypes in knee osteoarthritis? An explorative evaluation in the IMI-APPROACH cohort

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources