Toward designing human intervention studies to prevent osteoarthritis after knee injury: A report from an interdisciplinary OARSI 2023 workshop

Jackie L. Whittaker; Raneem Kalsoum; James Bilzon; Philip G. Conaghan; Kay Crossley; George R. Dodge; Alan Getgood; Xiaojuan Li; Elena Losina; Deborah J. Mason; Brian Pietrosimone; May Arna Risberg; Frank Roemer; David Felson; Adam G. Culvenor; Duncan Meuffels; Nicole Gerwin; Lee S. Simon; L. Stefan Lohmander; Martin Englund; Fiona E. Watt

Osteoarthritis and Cartilage Open (Jun 2024)

Toward designing human intervention studies to prevent osteoarthritis after knee injury: A report from an interdisciplinary OARSI 2023 workshop

Jackie L. Whittaker,
Raneem Kalsoum,
James Bilzon,
Philip G. Conaghan,
Kay Crossley,
George R. Dodge,
Alan Getgood,
Xiaojuan Li,
Elena Losina,
Deborah J. Mason,
Brian Pietrosimone,
May Arna Risberg,
Frank Roemer,
David Felson,
Adam G. Culvenor,
Duncan Meuffels,
Nicole Gerwin,
Lee S. Simon,
L. Stefan Lohmander,
Martin Englund,
Fiona E. Watt

Affiliations

Jackie L. Whittaker: Department of Physical Therapy, University of British Columbia, Vancouver, Canada; Arthritis Research Canada, Vancouver, Canada
Raneem Kalsoum: Department of Immunology and Inflammation, Imperial College London, London, UK
James Bilzon: Department for Health, University of Bath, Bath, UK; Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, UK
Philip G. Conaghan: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; NIHR Leeds Biomedical Research Centre, Leeds, UK
Kay Crossley: La Trobe Sport and Exercise Medicine Research Centre, School of Allied Health, Human Services and Sport, La Trobe University, Melbourne, Australia
George R. Dodge: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Mechano Therapeutics LLC, Philadelphia, PA, USA
Alan Getgood: Division of Orthopedic Surgery, Bone and Joint Institute, Fowler Kennedy Sport Medicine Clinic, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
Xiaojuan Li: Program of Advanced Musculoskeletal Imaging (PAMI), Cleveland Clinic, OH, USA; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, OH, USA
Elena Losina: Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, USA; Department of Orthopedic Surgery, Harvard Medical School, Boston, USA
Deborah J. Mason: Biomechanics and Bioengineering Research Centre Versus Arthritis, School of Biosciences, Cardiff University, Cardiff, UK
Brian Pietrosimone: Department of Exercise and Sport Science, University of North Carolina, USA
May Arna Risberg: Norwegian School Sport Sciences, Oslo, Norway; Division of Orthopedic Surgery, Oslo University Hospital, Oslo, Norway
Frank Roemer: Department of Radiology, Universitätsklinikum Erlangen & Friedrich- Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA
David Felson: Section of Rheumatology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA
Adam G. Culvenor: La Trobe Sport and Exercise Medicine Research Centre, School of Allied Health, Human Services and Sport, La Trobe University, Melbourne, Australia
Duncan Meuffels: Orthopedic and Sport Medicine Department, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Nicole Gerwin: Novartis BioMedical Research, Basel, Switzerland
Lee S. Simon: SDG LLC, Cambridge, MA, USA
L. Stefan Lohmander: Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden
Martin Englund: Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund University, Lund, Sweden
Fiona E. Watt: Department of Immunology and Inflammation, Imperial College London, London, UK; Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, University of Oxford, UK; Corresponding author. Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, Commonwealth Building, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.

Journal volume & issue: Vol. 6, no. 2
p. 100449

Abstract

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Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.

Published in Osteoarthritis and Cartilage Open

ISSN: 2665-9131 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the musculoskeletal system
Website: https://www.journals.elsevier.com/osteoarthritis-and-cartilage-open/

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