Conaghan, P.G. orcid.org/0000-0002-3478-5665, Katz, N., Hunter, D.J. et al. (8 more authors) (2025) Exploring a novel outcome measure of symptom progression in knee osteoarthritis utilizing a large randomized trial. Osteoarthritis and Cartilage, 33 (3). pp. 383-390. ISSN 1063-4584
Abstract
Objectives Explore a newly defined composite measure of symptom progression for knee osteoarthritis (KOA) in a large, randomized study of a potential disease-modifying osteoarthritis drug (DMOAD). Design Using longitudinal KOA studies, a potential composite endpoint of time to symptom progression was defined as the first occurrence of worsening of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain of ≥10 points with no improvement (≤9 point decrease) in WOMAC Function (0–100 scale). A post hoc analysis explored discrimination and association with structural outcomes in the sprifermin FORWARD trial through Years 3 and 5. All treatment arms of the intent-to-treat population were analyzed. Results Among the 549 FORWARD participants, 442 (80.5%) completed Year 3, and 378 (68.9%) completed Year 5. Sprifermin showed dose-dependent benefits in the time to symptom progression at Year 3 with hazard ratio (95% CI) for each sprifermin treatment arm vs placebo as follows: 100 μg every 6 months (Q6M), 0.51 (0.28, 0.93); 100 μg Q12M, 0.69 (0.40, 1.20); 30 μg Q6M, 0.89 (0.53, 1.50); and 30 μg Q12M, 0.80 (0.47, 1.35). Similar findings were seen through Year 5 and for a subgroup based on modern clinical trial inclusion criteria. There were increased numbers of knee replacements in symptom progressors (n=8, 5.6%) vs non-progressors (n=7, 1.7%). Conclusions The symptom progression endpoint discriminated between placebo and treatment responses in a post hoc analysis of a Phase 2 investigational DMOAD KOA trial. The endpoint requires validation and further exploration in DMOAD clinical trials.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Osteoarthritis, Knee, Sprifermin, Fibroblast growth factor 18, Treatment outcome |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Musculoskeletal Medicine & Imaging (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Jan 2025 13:59 |
Last Modified: | 06 Mar 2025 13:23 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.joca.2024.12.003 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221817 |