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Unraveling the confusion behind hyaluronic acid efficacy in the treatment of symptomatic knee osteoarthritis
Authors Miller LE , Altman R, McIntyre L
Received 16 April 2016
Accepted for publication 3 May 2016
Published 17 June 2016 Volume 2016:9 Pages 421—423
DOI https://doi.org/10.2147/JPR.S110675
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Michael Schatman
Larry E Miller,1 Roy D Altman,2 Louis F McIntyre3
1Miller Scientific Consulting, Inc., Asheville, NC, 2Department of Rheumatology, University of California Los Angeles, Los Angeles, CA, 3Northwell Physician Partners, Sleepy Hollow, NY, USA
Abstract: Hyaluronic acid (HA) is a commonly prescribed treatment for knee pain resulting from osteoarthritis (OA). Although numerous HA products have been approved for use by the US Food and Drug Administration, the efficacy of HA injections for knee OA remains disputed with meta-analyses and societal clinical guidelines drawing disparate conclusions. The American Academy of Orthopaedic Surgeons (AAOS) recently published a best-evidence systematic review and concluded that available data did not support the routine use of HA for knee OA. The purpose of the current article is to highlight issues that confound interpretation of meta-analyses on HA for knee OA, to provide realistic estimates of the true efficacy of HA injections in knee OA, and to provide commentary on the methods and conclusions from the AAOS systematic review. In general, the clinical benefit of HA is underestimated using conventional meta-analytic techniques. When accounting for differential control group effects in HA studies, it can be reasonably concluded that HA injections may be beneficial to an appreciable number of patients with knee OA. In addition, the systematic review methodology used by AAOS was questionable due to exclusion of numerous relevant studies and inclusion of studies that used HAs not approved for use in the US, both of which underestimated the true efficacy of HA injections. Overall, the efficacy of HA injections for knee OA is likely better than previously reported. Future clinical trials and meta-analyses should account for differential control group effects in order to avoid the continued confusion surrounding HA injection efficacy.
Keywords: effect size, hyaluronic acid, injection, knee, minimal important difference, osteoarthritis
Disclosure
RDA has served as a consultant to McNeil, Ferring, and QMed. LEM and LFM report no conflicts of interest in this work.
References
Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RF. The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum. 1987;30(8):914–918. | ||
van Saase JL, van Romunde LK, Cats A, Vandenbroucke JP, Valkenburg HA. Epidemiology of osteoarthritis: Zoetermeer survey. Comparison of radiological osteoarthritis in a Dutch population with that in 10 other populations. Ann Rheum Dis. 1989;48(4):271–280. | ||
Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. Ann Rheum Dis. 2001;60(2):91–97. | ||
Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet. 2005;365(9463):965–973. | ||
Dahl LB, Dahl IM, Engstrom-Laurent A, Granath K. Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies. Ann Rheum Dis. 1985;44(12):817–822. | ||
Smith MM, Ghosh P. The synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment. Rheumatol Int. 1987;7(3):113–122. | ||
Goldberg VM, Buckwalter JA. Hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease-modifying activity. Osteoarthritis Cartilage. 2005;13(3):216–224. | ||
Sadabad HN, Behzadifar M, Arasteh F, Behzadifar M, Dehghan HR. Efficacy of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: a systematic review and meta-analysis. Electron Physician. 2016;8(3):2115–2122. | ||
Wang F, He X. Intra-articular hyaluronic acid and corticosteroids in the treatment of knee osteoarthritis: a meta-analysis. Exp Ther Med. 2015;9(2):493–500. | ||
Bannuru RR, Vaysbrot EE, Sullivan MC, McAlindon TE. Relative efficacy of hyaluronic acid in comparison with NSAIDs for knee osteoarthritis: a systematic review and meta-analysis. Semin Arthritis Rheum. 2014;43(5):593–599. | ||
Miller LE, Block JE. US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: systematic review and meta-analysis of randomized, saline-controlled trials. Clin Med Insights Arthritis Musculoskelet Disord. 2013;6:57–63. | ||
Colen S, van den Bekerom MP, Mulier M, Haverkamp D. Hyaluronic acid in the treatment of knee osteoarthritis: a systematic review and meta-analysis with emphasis on the efficacy of different products. BioDrugs. 2012;26(4):257–268. | ||
Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE. Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthritis Cartilage. 2011;19(6):611–619. | ||
Bannuru RR, Natov NS, Obadan IE, Price LL, Schmid CH, McAlindon TE. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum. 2009;61(12):1704–1711. | ||
Rutjes AW, Juni P, da Costa BR, Trelle S, Nuesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012;157(3):180–191. | ||
Strand V, McIntyre LF, Beach WR, Miller LE, Block JE. Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials. J Pain Res. 2015;8:217–228. | ||
Jevsevar D, Donnelly P, Brown GA, Cummins DS. Viscosupplementation for osteoarthritis of the knee: a systematic review of the evidence. J Bone Joint Surg Am. 2015;97(24):2047–2060. | ||
Lund K, Vase L, Petersen GL, Jensen TS, Finnerup NB. Randomised controlled trials may underestimate drug effects: balanced placebo trial design. PLoS One. 2014;9(1):e84104. | ||
Fountoulakis KN, Moller HJ. Antidepressant drugs and the response in the placebo group: the real problem lies in our understanding of the issue. J Psychopharmacol. 2012;26(5):744–750. | ||
Cohen J. Statistical Power Analysis for the Behavioral Sciences. Hillside, NJ: Lawrence Erlbaum Associates; 1987. | ||
American Academy of Orthopaedic Surgeons [webpage on the Internet]. Treatment of Osteoarthritis of the Knee: Evidence-Based Guideline. 2013. Available from: http://www.aaos.org/research/guidelines/TreatmentofOsteoarthritisoftheKneeGuideline.pdf. Accessed April 15, 2016. | ||
Bannuru RR, McAlindon TE, Sullivan MC, Wong JB, Kent DM, Schmid CH. Effectiveness and implications of alternative placebo treatments: a systematic review and network meta-analysis of osteoarthritis trials. Ann Intern Med. 2015;163(5):365–372. | ||
Johnston BC, Thorlund K, Schunemann HJ, et al. Improving the interpretation of quality of life evidence in meta-analyses: the application of minimal important difference units. Health Qual Life Outcomes. 2010;8:116. | ||
Brandt KD, Block JA, Michalski JP, Moreland LW, Caldwell JR, Lavin PT. Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group. Clin Orthop Relat Res. 2001;(385):130–143. | ||
Jorgensen A, Stengaard-Pedersen K, Simonsen O, et al. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year. Ann Rheum Dis. 2010;69(6):1097–1102. | ||
Lohmander LS, Dalen N, Englund G, et al. Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Multicentre Trial Group. Ann Rheum Dis. 1996;55(7):424–431. | ||
Puhl W, Bernau A, Greiling H, et al. Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study. Osteoarthritis Cartilage. 1993;1(4):233–241. | ||
Rolf CG, Engstrom B, Ohrvik J, Valentin A, Lilja B, Levine DW. A comparative study of the efficacy and safety of hyaluronan viscosupplements and placebo in patients with symptomatic and arthroscopy-verified cartilage pathology. J Clin Res. 2005;8:15–32. | ||
Wobig M, Dickhut A, Maier R, Vetter G. Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee. Clin Ther. 1998;20(3):410–423. | ||
Altman RD, Akermark C, Beaulieu AD, Schnitzer T; Durolane International Study Group. Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee. Osteoarthritis Cartilage. 2004;12(8):642–649. | ||
Petrella RJ, Cogliano A, Decaria J. Combining two hyaluronic acids in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Clin Rheumatol. 2008;27(8):975–981. | ||
Surgeons AAoO [webpage on the Internet]. Treatment of Osteoarthritis of the Knee: Evidence-Based Guideline. 2nd ed. 2013. Available from: http://www.aaos.org/uploadedFiles/PreProduction/Quality/Guidelines_and_Reviews/Osteoarthritis%20of%20the%20Knee%20-%20non-arthroplasty.pdf. Accessed April 15, 2016. | ||
Campbell KA, Erickson BJ, Saltzman BM, et al. Is local viscosupplementation injection clinically superior to other therapies in the treatment of osteoarthritis of the knee: a systematic review of overlapping meta-analyses. Arthroscopy. 2015;31(10):2036.e14–2045.e14. | ||
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(1):46–54. | ||
McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(3):363–388. |
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