Exploring a novel outcome measure of symptom progression in knee osteoarthritis utilizing a large randomized trial

Philip G Conaghan; Nathaniel Katz; David J Hunter; Ali Guermazi; Marc C Hochberg; Kenneth Somberg; Julia Clive; Chris Knight; Mary Johnson; Luping Zhao; Niti Goel

doi:10.1016/j.joca.2024.12.003

Exploring a novel outcome measure of symptom progression in knee osteoarthritis utilizing a large randomized trial

Osteoarthritis Cartilage. 2024 Dec 28:S1063-4584(24)01502-4. doi: 10.1016/j.joca.2024.12.003. Online ahead of print.

Authors

Philip G Conaghan¹, Nathaniel Katz², David J Hunter³, Ali Guermazi⁴, Marc C Hochberg⁵, Kenneth Somberg⁶, Julia Clive⁶, Chris Knight⁶, Mary Johnson⁶, Luping Zhao⁶, Niti Goel⁷

Affiliations

¹ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, & NIHR Leeds Biomedical Research Centre, Leeds, UK. Electronic address: P.Conaghan@leeds.ac.uk.
² Tufts University, Department of Anesthesiology & Perioperative Medicine, Boston, MA, USA; Ein Sof Innovation, Boston, MA, USA.
³ Sydney Musculoskeletal Health, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Rheumatology Department, Royal North Shore Hospital, St Leonards, Australia.
⁴ Boston University School of Medicine, Radiology, Boston, MA, USA; VA Boston Healthcare System, Radiology, Boston, MA, USA.
⁵ Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
⁶ Formation Bio, Inc., Research and Development, New York City, NY, USA.
⁷ Formation Bio, Inc., Research and Development, New York City, NY, USA; Caduceus Biomedical Consulting, LLC, Durham, NC, USA; Duke University School of Medicine, Department of Medicine, Division of Rheumatology, Durham, NC, USA.

PMID: 39734047
DOI: 10.1016/j.joca.2024.12.003

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), 0.511 (0.282, 0.926); 100 μg Q12M, 0.689 (0.397, 1.196); 30 μg Q6M, 0.891 (0.530, 1.499); and 30 μg Q12M, 0.799 (0.472, 1.351). 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.

Trial number: NCT01919164.

Keywords: Fibroblast growth factor 18; Knee; Osteoarthritis; Sprifermin; Treatment outcome.

Associated data

ClinicalTrials.gov/NCT01919164