Objective To compare the efficacy of an exercise and education programme with open-label placebo given as intra-articular injections of inert saline on pain and function in individuals with knee osteoarthritis (OA).
Methods In this open-label, randomised controlled trial, we recruited adults aged ≥50 years with symptomatic and radiographically confirmed knee OA in Denmark. Participants were randomised 1:1 to undergo an 8-week exercise and education programme or four intra-articular saline injections over 8 weeks. Primary outcome was change from baseline to week 9 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale (range 0 (worst)–100 (best)). Prespecified equivalence margins of ±8 KOOS pain points were chosen for the demonstration of comparable efficacy. Key secondary outcomes were the KOOS function and quality of life subscales, and patients’ global assessment of disease impact.
Results 206 adults were randomly assigned: 102 to exercise and education and 104 to intra-articular saline injections. For the primary outcome, the least squares mean changes in KOOS pain were 10.0 for exercise and education and 7.3 for saline injections (difference 2.7 points, 95% CI −0.6 to 6.0; test for equivalence p=0.0008). All group differences in the key secondary outcomes respected the predefined equivalence margins. Adverse events and serious adverse events were similar in the two groups.
Conclusion In individuals with knee OA, an 8-week exercise and education programme provided efficacy for symptomatic and functional improvements equivalent to that of four open-label intra-articular saline injections over 8 weeks.
Trial registration number NCT03843931.
- physical therapy modalities
Data availability statement
Data are available upon reasonable request. Data can be shared upon reasonable request to the corresponding author: email@example.com.
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Handling editor Josef S Smolen
Twitter @DrRChristensen, @CBartholdy, @ProfDavidHunter, @henriksen_mh
Contributors EAB and MH had full access to all of the data in the study and take responsibility for the data and the accuracy of the data analysis. Concept and design: EAB, RC, HB, LEK and MH conceived and designed the trial and the protocol that was reviewed and adjusted following important scientific and practical advice from KE, CB, DJH and RA. Drafting of the manuscript: EAB and MH. Statistical analysis: EAB, RC and MH. Obtained funding: EAB, HB and MH. Administrative, technical or material support: EAB, RC, KE, AO, JG-M, HB and MH. Supervision: DJH, RA, HB and MH. Acquisition, analysis or interpretation of data, and critical revision of the manuscript for important intellectual content: all authors. MH is the guarantor.
Funding This study was supported by grants from The Lundbeck Foundation, The Danish Physiotherapists Association and Aase og Ejnar Danielsens Fund. The Parker Institute, Bispebjerg and Frederiksberg Hospital, is supported by a core grant from the Oak Foundation (OCAY-18–774-OFIL).
Disclaimer The funders had no role in the design and conduct of the study; collection, analysis and interpretation of the data; preparation, review or approval of the manuscript; or decision to submit the manuscript for publication. All researchers are independent from funders and all authors both external and internal, had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Competing interests EAB reports grants from The Lundbeck Foundation, The Danish Physiotherapists Association and The Oak Foundation during the conduct of the study; and membership in the Danish Physiotherapist Association. LEK reports receiving fees for speaking and consultancy from Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly and Janssen pharmaceuticals. JG-M reports personal fees from AbbVie, Eli-Lilly and BK Ultrasound; and grants and personal fees from Novartis outside the submitted work. DJH reports personal fees from Pfizer, Lilly, TLCBio, Novartis, Tissuegene and Biobone outside the submitted work. RA reports personal fees from Novartis, Pfizer and Sorrento; others from Olatec, GSK, Noven, Sanofi and Teva outside the submitted work; and consultancy for GSK, Noven, Novartis, Olatec, Pfizer, Sanofi, Sorrento and Teva. MH reports grants from The Oak Foundation and Aase & Ejnar Danielsens Foundation during the conduct of the study; personal fees from Thuasne Group, outside the submitted work; and membership of Danish Physiotherapist Association.
Provenance and peer review Not commissioned; externally peer reviewed.
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