Comparative Effectiveness of Pharmacologic Interventions for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis
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Abstract
Background:
The relative efficacy of available treatments of knee osteoarthritis (OA) must be determined for rational treatment algorithms to be formulated.
Purpose:
To examine the efficacy of treatments of primary knee OA using a network meta-analysis design, which estimates relative effects of all treatments against each other.
Data Sources:
MEDLINE, EMBASE, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials from inception through 15 August 2014, and unpublished data.
Study Selection:
Randomized trials of adults with knee OA comparing 2 or more of the following: acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib, intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and IA placebo.
Data Extraction:
Two reviewers independently abstracted study data and assessed study quality. Standardized mean differences were calculated for pain, function, and stiffness at 3-month follow-up.
Data Synthesis:
Network meta-analysis was performed using a Bayesian random-effects model; 137 studies comprising 33 243 participants were identified. For pain, all interventions significantly outperformed oral placebo, with effect sizes from 0.63 (95% credible interval [CrI], 0.39 to 0.88) for the most efficacious treatment (hyaluronic acid) to 0.18 (CrI, 0.04 to 0.33) for the least efficacious treatment (acetaminophen). For function, all interventions except IA corticosteroids were significantly superior to oral placebo. For stiffness, most of the treatments did not significantly differ from one another.
Limitation:
Lack of long-term data, inadequate reporting of safety data, possible publication bias, and few head-to-head comparisons.
Conclusion:
This method allowed comparison of common treatments of knee OA according to their relative efficacy. Intra-articular treatments were superior to nonsteroidal anti-inflammatory drugs, possibly because of the integrated IA placebo effect. Small but robust differences were observed between active treatments. All treatments except acetaminophen showed clinically significant improvement from baseline pain. This information, along with the safety profiles and relative costs of included treatments, will be helpful for individualized patient care decisions.
Primary Funding Source:
Agency for Healthcare Research and Quality.
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Published In
Annals of Internal Medicine
Volume 162 • Number 1 • 6 January 2015
Pages: 46 - 54
History
Published online: 6 January 2015
Published in issue: 6 January 2015
Keywords
Copyright
© 2015 American College of Physicians.
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Comparative Effectiveness of Pharmacologic Interventions for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis. Ann Intern Med.2015;162:46-54. [Epub 6 January 2015]. doi:10.7326/M14-1231
Comparative Effectiveness of Pharmacologic Interventions for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis. Ann Intern Med.2015;162:46-54. [Epub 6 January 2015]. doi:10.7326/M14-1231
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Pharmacologic Interventions for Knee Osteoarthritis
The best evidence is that intraarticular hyaluronic acid has no clinically meaningful benefit for knee osteoarthritis compared to an intraarticular placebo injection (5). The guidelines of the American Academy of Orthopedic Physicians contains a strong recommendation against the use of hyaluronic acid for treatment of knee osteoarthritis (6). The review by Bannuru et al. provides no basis for reconsidering current guidelines.
Despite the lack of evidence supporting its use, injections of hyaluronic acid for knee osteoarthritis are used widely. It is unfortunate that this paper may well be misquoted in other popular health media and in advertisements as providing evidence for the benefits of hyaluronic acid.
References
1. Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE. Comparative effectivenesss of pharmacologic interventions for knee osteoarthritis. Ann Int Med 2015; 162: 46-54.
2. Mandl LA, Losina E. Relative efficacy of knee osteoarthritis treatments: Are all placebos created equal? Ann Int med 2015; 162:71-2.
3. Altman R. Next round on hyaluronic acid: Better even than acetaminophen? New data call AAOS recommendations into question? http://www.medpagetoday.com/Rheumatology/Arthritis /49 1/23/2015.
4. Norton A. Knee arthritis drugs beat placebos, but study finds no clear winner. Health Day http://consumerhealthday.com January 6, 2015, accesed January 26, 2015.
5. Rutjes AWS, Juni P, da Costa BR, Trelle S, Nuesch E, Reichenbach S. Viscosupplementation for osteoarhritis of the knee. Ann Intern Med 2012; 157:180-91.
6. American Academy of Orthopedic Surgeons. Treament of osteoarthritis of the knee:evidence-based guidelines. 2nd edition. Rosement, IL: American Academy of Orthopedic Surgeons; 2013. Accessed at www.aaos.org January 29, 2015
Author's Response
Our network meta-analysis enabled us to estimate the comparative effectiveness of intra-articulars relative to oral agents, and rank these effects in a way that has clinical utility.1 The fact that the derived comparative effect may incorporate a component of a placebo response should prompt thought and discussion as to how to reformulate how we think about its role in therapy and practice of medicine. Therefore, we should think carefully before making strong negative recommendations for therapeutic products that have good comparative effectiveness, especially for conditions for which use of the limited number of alternatives is often precluded by comorbid contra-indications. These complex considerations may explain why there are differences between consensus recommendations from different groups in regard to products such as HA.2-4
1. Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE. Comparative Effectiveness of Pharmacologic Interventions for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis. Annals of internal medicine. Jan 6 2015;162(1):46-54.
2. Brown GA. AAOS clinical practice guideline: treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. The Journal of the American Academy of Orthopaedic Surgeons. Sep 2013;21(9):577-579.
3. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis care & research. Apr 2012;64(4):465-474.
4. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. Mar 2014;22(3):363-388.