Raveendhara R. Bannuru, MD; Christopher H. Schmid, PhD; David M. Kent, MD; Elizaveta E. Vaysbrot, MD; John B. Wong, MD; Timothy E. McAlindon, MD
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality (AHRQ).
Acknowledgment: The authors thank Matthew Sullivan for his contributions to this work.
Grant Support: By the AHRQ (grants F32HS021396 and R01-HS018574; Drs. Bannuru and Schmid, respectively).
Disclosures: Dr. Bannuru reports grants from AHRQ during the conduct of the study. Dr. Wong reports grants from Patient-Centered Outcomes Research Institute and National Institutes of Health National Center for Complementary and Alternative Medicine and nonfinancial support from European League Against Rheumatism outside the submitted work. Dr. McAlindon reports grants from Croma, Flexion Therapeutics, National Institutes of Health, and AHRQ; and personal fees from Bioventus outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1231.
Requests for Single Reprints: Raveendhara R. Bannuru, MD, Center for Treatment Comparison and Integrative Analysis, Division of Rheumatology, Tufts Medical Center, 800 Washington Street, Box 406, Boston, MA 02111; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Bannuru, Vaysbrot, and McAlindon: Center for Treatment Comparison and Integrative Analysis, Division of Rheumatology, Tufts Medical Center, 800 Washington Street, Boston, MA 02111.
Drs. Kent and Wong: Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 800 Washington Street, Boston, MA 02111.
Dr. Schmid: Brown University School of Public Health, 121 South Main Street, Providence, RI 02912.
Author Contributions: Conception and design: R.R. Bannuru, C.H. Schmid, T.E. McAlindon.
Analysis and interpretation of the data: R.R. Bannuru, C.H. Schmid, D.M. Kent, J.B. Wong, T.E. McAlindon.
Drafting of the article: R.R. Bannuru, C.H. Schmid, J.B. Wong.
Critical revision of the article for important intellectual content: R.R. Bannuru, C.H. Schmid, D.M. Kent, E.E. Vaysbrot, J.B. Wong, T.E. McAlindon.
Final approval of the article: R.R. Bannuru, C.H. Schmid, D.M. Kent, E.E. Vaysbrot, J.B. Wong, T.E. McAlindon.
Provision of study materials or patients: R.R. Bannuru.
Statistical expertise: R.R. Bannuru, C.H. Schmid.
Obtaining of funding: R.R. Bannuru.
Administrative, technical, or logistic support: R.R. Bannuru, E.E. Vaysbrot.
Collection and assembly of data: R.R. Bannuru, E.E. Vaysbrot.
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. Ann Intern Med. 2015;162:46-54. doi: 10.7326/M14-1231
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Published: Ann Intern Med. 2015;162(1):46-54.
The relative efficacy of available treatments of knee osteoarthritis (OA) must be determined for rational treatment algorithms to be formulated.
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.
MEDLINE, EMBASE, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials from inception through 15 August 2014, and unpublished data.
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.
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.
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.
Lack of long-term data, inadequate reporting of safety data, possible publication bias, and few head-to-head comparisons.
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.
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Rheumatology, Healthcare Delivery and Policy, Osteoarthritis.
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