Placebo effects after local intra-articular therapy


Osteoarthritis (OA) is a highly prevalent condition that imposes substantial burden on the individuals affected. Presently there are limited treatments available to control symptoms. Current United States Food and Drug Administration (FDA) and European Medicine Agency approved agents consist of corticosteroids and viscosupplements (hyaluronate). These are not first-line recommended therapies from treatment guidelines based on their limited efficacy profiles. This is in large part due to the inability to achieve a minimum clinically important difference over placebo. When considering clinical trial design, the challenges of which placebo to choose, its volume, injection frequency, the use of injection guidance, concomitant local anaesthetic use, patient baseline disease presentation (bilateral versus unilateral disease, concomitant presence of inflammatory features/effusion, disease severity, baseline pain) all create substantial opportunity for heterogeneity in what is already a challenging clinical trial environment.

As the placebo effect can be attributed to the individual or related to the study protocol, assessment of the placebo effect utilising individual patient data (IPD) meta-analysis will give insight into the different predictors of placebo response and influence subsequent implementation of clinical designs with lowered placebo response.


Using IPD, a number of analyses of placebo-controlled trial data from different intra-articular injection trials for osteoarthritis will be conducted to ascertain the mechanisms behind placebo response in intra-articular trials in osteoarthritis. Placebo randomized control trials of intra-articular

glucocorticoids and viscosupplements will be identified via a systematic literature review. Intervention characteristics, trial characteristics, disease severity and outcomes will be analysed.


Ongoing project

Protocol and publications


S. (Shirley) P. Yu 1
M. (Manuela) Ferreira 1
M. (Marienke) van Middelkoop 3
S. (Sita) M.A. Bierma-Zeinstra 2, 3
W. (Weiya) Zhang 4, 5
D. (David) J. Hunter 1

1. Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, NSW Australia
2. Department of Orthopedic Surgery, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
3. Department of General Practice, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
4. Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham, United Kingdom
5. Arthritis Research UK Pain Centre, Nottingham, United Kingdom