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Predictors of Placebo Response to Local (Intra-Articular) Therapy In Osteoarthritis: An Individual Participant Data Meta-Analysis

Lookup NU author(s): Dr Ismael Atchia, Professor Fraser Birrell



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology. Objective: We undertook this study to evaluate potential predictors of placebo response with intra-articular (IA) injections for knee/hip osteoarthritis (OA) using individual participant data (IPD) from existing trials. Methods: Randomized placebo-controlled trials evaluating IA glucocorticoid or hyaluronic acid published to September 2018 were selected. IPD for disease characteristics and outcome measures were acquired. Potential predictors of placebo response included participant characteristics, pain severity, intervention, and trial design. Placebo response was defined as at least a 20% reduction in baseline pain. Logistic regression models and odds ratios were computed as effect measures to evaluate patient and pain mechanisms and then pooled using a random effects model. Generalized mixed-effect models were applied to intervention and trial characteristics. Results: Of 56 eligible trials, 6 shared data, and these were combined with the existing 4 OA Trial Bank studies, yielding 10 studies with IPD of 621 placebo participants for analysis. In the total placebo population, at short-term follow-up, the use of local anesthetic and ultrasound guidance were associated with reduced odds of placebo response. At midterm follow-up, mid- to long-term trial duration was associated with increased odds of placebo response, and worse baseline function scores were associated with reduced odds of a placebo response. Conclusion: The administration of local anesthetics or ultrasound guidance may reduce IA placebo response at short-term follow-up. At midterm follow-up, participants with worse baseline function scores may be less likely to respond to IA placebo, and mid- to long-term trial duration may enhance the placebo response. Further studies are required to corroborate these potential predictors of IA placebo response.

Publication metadata

Author(s): Yu SP, van Middelkoop M, Deveza LA, Ferreira ML, Bierma-Zeinstra S, Zhang W, Atchia I, Birrell F, Bhagavath V, Hunter DJ

Publication type: Article

Publication status: Published

Journal: Arthritis Care and Research

Year: 2024

Volume: 76

Issue: 2

Pages: 208-224

Print publication date: 01/02/2024

Online publication date: 31/07/2023

Acceptance date: 26/07/2023

Date deposited: 08/11/2023

ISSN (print): 2151-464X

ISSN (electronic): 2151-4658

Publisher: John Wiley and Sons Inc.


DOI: 10.1002/acr.25212

PubMed id: 37525486


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