Subgroup analysis on the effectiveness of intra-articular glucocorticoid injections in patients with knee or hip osteoarthritis


To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials.

Methods: Randomized trials evaluating one or more IA glucocorticoid preparation in patients with knee or hip osteoarthritis, published from 1995 up to June 2012 were selected from the literature. Individual patient data obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). The subgroup factors assessed included severe pain (≥70 points, 0 to 100 scale) and signs of inflammation (dichotomized in present or not) at baseline. Multilevel regression analyses were applied to estimate the magnitude of the effects in the subgroups with the individuals nested within each study.


Seven out of 43 published randomized clinical trials (n=620) were included. Patients with severe baseline pain had a significantly larger reduction in short-term pain, but not in mid-and long-term pain, compared to those with less severe pain at baseline (Mean Difference 13.91; 95% 1.50 to 26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points.


This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short term follow-up than those with less severe pain at baseline.

Protocol and publications


M. (Marienke) van Middelkoop 13
N. (Nigel) Arden 1
I. (Ismaël) Atchia 2
F. (Fraser) Birrell 2
J. (Jeannie) Chao 3
M. (Maria) U. Rezende 4
R. (Robert) G.W. Lambert 5
P. (Philippe) Ravaud 6
J.W. (Hans) Bijlsma 7
M. (Michael) Doherty 8
K. (Krysia) Dziedzic 9
S. (Stefan) Lohmander 10
T. (Timothy) E. McAlindon 11
W. (Weiya) Zhang 12
S. (Sita) M.A. Bierma-Zeinstra 13

1. Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, OX3 7LD, UK
2. Northumbria Healthcare NHS Foundation Trust and University of Newcastle, UK
3. UCSD School of Medicine, La Jolla, CA, USA
4. Instituto de Ortopedia e traumatologia, Faculdade de Medicina, HCFMUSP, Sao Paulo
5. Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton, Canada
6. Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité, Paris, France
7. University Medical Center Utrecht, Department of Rheumatology & Clinical Immunology, Utrecht, The Netherlands
8. Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK
9. Arthritis Research UK Primary Care Centre, Primary Care Sciences Keele University, UK
10. Lund University, Department of Orthopaedics, Clinical Sciences Lund, Sweden
11. Tufts University, Department of Medicine, Boston, USA
12. Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK
13. Erasmus MC Medical University Center Rotterdam, Department of General Practice, The Netherlands