Abstract
Objective. To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of “need for joint replacement surgery,” for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA).
Methods. New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons’ indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA.
Results. In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%–12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0–100) + physical function (0–100) > 80].
Conclusion. These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define “nonresponders” to disease-modifying drugs in OA clinical trials.
Footnotes
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Supported by unrestricted grants from OARSI and OMERACT and pharmaceutical companies Pfizer, Expansciences, Novartis, Negma Lerads, Rottapharm-Madaus, Fidia, and Pierre Fabre Santé Laboratories. Procter and Gamble Pharmaceuticals provided unrestricted access to placebo data from the KOSTAR study and an unrestricted grant to COB. LSL was supported by the Swedish Research Council; JAS was supported by the National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research). MSA holds a K24 award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and is partially supported by the Agency for Healthcare Research and Quality through funding of the Houston Center for Education and Research on Therapeutics (CERT). RLM is supported by NIH Training Grant T32 AR48522-06. P. Coste is an employee of Expanscience; A. Lanzarotti and E. Tajana-Messi are employees of IBSA; L.C. Rovati and G. Giacovelli are employees of Rottapharm-Madaus; COB served as a consultant and investigator for Procter and Gamble Pharmaceuticals, Novartis, and Merck and received an unrestricted grant from P&G Pharmaceuticals; LM has received a speaker honorarium and travel grant from Servier. JAS has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient and URL pharmaceuticals.