Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomized trials: A systematic review and network meta-analysis

Tiago V Pereira¹, Pakeezah Saadat², Pavlos Bobos³, Samir M Iskander⁴, Nicolas S Bodmer⁵, Martina Rudnicki⁶, Henry Dan Kiyomoto⁷, Thais Montezuma⁸, Matheus O Almeida⁸, Rishi Bansal¹, Pai-Shan Cheng⁹, Jason W Busse¹⁰, Alex J Sutton¹¹, Peter Tugwell¹², Gillian A Hawker¹³, Peter Jüni¹⁴, Bruno R da Costa¹⁵

Affiliations

¹ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
² Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
³ School of Physical Therapy, Western University, London, ON, Canada; Western's Bone and Joint Institute, Western University, London, ON, Canada.
⁴ Schulich School of Medicine, University of Western Ontario, London N6A 3K7, Canada.
⁵ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; University of Zurich, Medical Faculty, CH-8091 Zurich, Switzerland.
⁶ Institute of Ophthalmology, University College London, London, UK.
⁷ Department of Physiotherapy, Faculty of the Americas (FAM), São Paulo, Brazil.
⁸ Health Technology Assessment Unit, Oswaldo Cruz German Hospital, São Paulo, Brazil.
⁹ Biostatistics Division, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Anesthesia, McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹¹ Department of Population Health Sciences, University of Leicester, Leicester, UK.
¹² Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
¹³ Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁴ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁵ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Institute of Primary Health Care (BIHAM), University of Bern, Switzerland. Electronic address: bruno.dacosta@ndph.ox.ac.uk.

PMID: 39265924
DOI: 10.1016/j.joca.2024.08.014

Free article

Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomized trials: A systematic review and network meta-analysis

Tiago V Pereira et al. Osteoarthritis Cartilage. 2025 Feb.

Free article

. 2025 Feb;33(2):207-217.

doi: 10.1016/j.joca.2024.08.014. Epub 2024 Sep 10.

Authors

Affiliations

¹ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
² Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
³ School of Physical Therapy, Western University, London, ON, Canada; Western's Bone and Joint Institute, Western University, London, ON, Canada.
⁴ Schulich School of Medicine, University of Western Ontario, London N6A 3K7, Canada.
⁵ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; University of Zurich, Medical Faculty, CH-8091 Zurich, Switzerland.
⁶ Institute of Ophthalmology, University College London, London, UK.
⁷ Department of Physiotherapy, Faculty of the Americas (FAM), São Paulo, Brazil.
⁸ Health Technology Assessment Unit, Oswaldo Cruz German Hospital, São Paulo, Brazil.
⁹ Biostatistics Division, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Anesthesia, McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹¹ Department of Population Health Sciences, University of Leicester, Leicester, UK.
¹² Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
¹³ Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁴ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁵ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Institute of Primary Health Care (BIHAM), University of Bern, Switzerland. Electronic address: bruno.dacosta@ndph.ox.ac.uk.

PMID: 39265924
DOI: 10.1016/j.joca.2024.08.014

Abstract

Objective: To quantify the effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis (OA) through a systematic review and Bayesian random-effects network meta-analysis.

Design: We searched CENTRAL and regulatory agency websites (inception-2023) for large, English-language, randomized controlled trials (RCTs) (≥100 patients/group) examining any intra-articular intervention.

Primary outcome: pain intensity.

Secondary outcomes: physical function and safety outcomes. Pain and function outcomes were analyzed at 2, 6, 12, 24, and 52 weeks post-randomization, and presented as standardized mean differences (SMDs) (95% credible intervals, 95% CrI). The prespecified minimal clinically important between-group difference (MID) was -0.37 SMD. Safety outcomes were presented as odds ratios (OR) (95% CrI).

Findings: Among 57 RCTs (22,795 participants) examining 18 intra-articular interventions, usual care or placebo, treatment effects were larger in 35 high-risk-of-bias trials than in 22 low/unclear-risk-of-bias trials. In the main analysis (excluding high-risk-of-bias trials), triamcinolone had the highest probabilities of reaching the MID at weeks 2 and 6 (75.3% and 90%, respectively) with corresponding SMDs of -0.48 (95% CrI,-0.85 to -0.10) and -0.53 (95% CrI,-0.79 to -0.27) compared to placebo (1 trial). The complex homeopathic products Tr14/Ze14 showed therapeutic potential at week 6 compared to placebo (SMD:-0.42, 95% CrI,-0.71 to -0.11, 63.5% probability of reaching the MID, 1 trial). Hyaluronic acid had no effect on pain (SMD:-0.04, 95% CrI,-0.19 to 0.11, 11 trials) but a higher risk of dropouts due to adverse events (OR: 2.01, 95% CrI,1.08 to 3.77) and serious adverse events (OR: 1.86, 95% CrI, 1.16 to 3.03) than placebo.

Conclusion: Triamcinolone had the highest probabilities to have a treatment effect beyond the MID at weeks 2-6. Large RCTs with lower risk of bias indicate that the effects of 16 intra-articular interventions in knee or hip OA were smaller than the MID, and that most were consistent with placebo effects. Lack of evidence of long-term effectiveness underscores the need for further research beyond 24 weeks.

Keywords: Hip; Injection; Intra-articular; Knee; Osteoarthritis; Pain.

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Conflict of interest statement

Declaration of Competing Interest Peter Tugwell is an advisory committee member of the Canadian Reformulary Group Inc., a company that reviews evidence for health insurance companies' employer drug plans. He is also the unpaid Chair of the Management Group of OMERACT, a registered non-profit independent medical research organization dedicated to improving health outcomes for patients with musculoskeletal conditions. OMERACT receives arms-length funding from 11 companies (AbbVie, AstraZeneca, Aurinia, BMS, Centrexion, GSK, Horizon Pharma Inc., Janssen, Novartis, Pfizer, and Sparrow). The remaining authors declare no conflicts of interest.

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Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomized trials: A systematic review and network meta-analysis

Affiliations

Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomized trials: A systematic review and network meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

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