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Cost Effectiveness of Intra-Articular Hyaluronic Acid and Disease-Modifying Drugs in Knee Osteoarthritis

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Abstract

Background

The place of disease-modifying osteoarthritis drugs (DMOADs) and intra-articular hyaluronic acid (IAHA) in the therapeutic arsenal for knee osteoarthritis (OA) remains uncertain. Indeed, these treatments have demonstrated symptomatic efficacy but no efficacy for disease modification.

Objective

This report reviews the cost effectiveness of IAHA and DMOADs used in the treatment of knee OA.

Methods

A systematic literature search of the MEDLINE, Scopus, EMBASE and Cochrane databases was performed independently by two rheumatologists who used the same predefined eligibility criteria to identify relevant articles. Papers without abstracts and in languages other than English or French were excluded. Extracted costs were annualised and converted to 2015 euros (€) using the Consumer Price Index of the relevant countries and the 2013 Purchasing Power Parities between these countries and the European Union average.

Results

A total of 95 abstracts were selected, and 13 articles were considered for the review: nine articles on IAHA and four on DMOADs. Only one article directly compared different IAHA compounds. Articles showed substantial heterogeneity in methodological approaches. The incremental cost-effectiveness ratios (ICERs) ranged from €4000 to €57,550 and from €240 to €53,225 per quality-adjusted life-year (QALY) gained for DMOADs and IAHA, respectively.

Conclusions

This review highlights substantial heterogeneity between studies, ranging from a cost saving (or dominating) position to very high ICERs, far above the acceptability threshold of €50,000/QALY. Additional research is needed to determine reliable and robust ICER estimates for knee OA therapies.

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References

  1. Felson DT, Zhang Y, Hannan MT, Naimark A, Weissman BN, Aliabadi P, et al. The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum. 1995;38:1500–5.

    Article  CAS  PubMed  Google Scholar 

  2. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2163–96.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Horizon 2020—European Commission. Horiz. 2020. http://ec.europa.eu/programmes/horizon2020/. Accessed 13 Apr 2015.

  4. Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull. 2013;105:185–99.

    Article  PubMed  Google Scholar 

  5. Guillemin F, Rat AC, Mazieres B, Pouchot J, Fautrel B, Euller-Ziegler L, et al. Prevalence of symptomatic hip and knee osteoarthritis: a two-phase population-based survey. Osteoarthr Cartil. 2011;19:1314–22.

    Article  CAS  Google Scholar 

  6. Jordan JM, Helmick CG, Renner JB, Luta G, Dragomir AD, Woodard J, et al. Prevalence of knee symptoms and radiographic and symptomatic knee osteoarthritis in African Americans and Caucasians: the Johnston County Osteoarthritis Project. J Rheumatol. 2007;34:172–80.

    PubMed  Google Scholar 

  7. Jordan JM, Helmick CG, Renner JB, Luta G, Dragomir AD, Woodard J, et al. Prevalence of hip symptoms and radiographic and symptomatic hip osteoarthritis in African Americans and Caucasians: the Johnston County Osteoarthritis Project. J Rheumatol. 2009;36:809–15.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Andrianakos AA, Kontelis LK, Karamitsos DG, Aslanidis SI, Georgountzos AI, Kaziolas GO, et al. Prevalence of symptomatic knee, hand, and hip osteoarthritis in Greece. The ESORDIG study. J Rheumatol. 2006;33:2507–13.

    PubMed  Google Scholar 

  9. Salaffi F, De Angelis R, Grassi W, MArche Pain Prevalence, INvestigation Group (MAPPING) study. Prevalence of musculoskeletal conditions in an Italian population sample: results of a regional community-based study. I. The MAPPING study. Clin Exp Rheumatol. 2005;23:819–28.

    CAS  PubMed  Google Scholar 

  10. Grotle M, Hagen KB, Natvig B, Dahl FA, Kvien TK. Prevalence and burden of osteoarthritis: results from a population survey in Norway. J Rheumatol. 2008;35:677–84.

    PubMed  Google Scholar 

  11. Principaux tableaux—Eurostat. http://ec.europa.eu/eurostat/web/population-demography-migration-projections/population-data/main-tables. Accessed 24 Jul 2015.

  12. McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 2014;22:363–88.

    Article  CAS  Google Scholar 

  13. Brown GA. AAOS clinical practice guideline: treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. J Am Acad Orthop Surg. 2013;21:577–9.

    PubMed  Google Scholar 

  14. Bruyère O, Cooper C, Pelletier J-P, Maheu E, Rannou F, Branco J, et al. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting. Semin Arthritis Rheum. 2016;45:S3–11.

    Article  PubMed  Google Scholar 

  15. PICO ontology| Cochrane Linked Data (beta). http://linkeddata.cochrane.org/pico-ontology. Accessed 3 Sep 2015.

  16. Cochrane handbook for systematic reviews of interventions. http://handbook-5-1.cochrane.org/. Accessed 7 May 2018.

  17. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833–40.

    CAS  PubMed  Google Scholar 

  18. Gandek B, Ware JE, Aaronson NK, Apolone G, Bjorner JB, Brazier JE, et al. Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol. 1998;51:1171–8.

    Article  CAS  PubMed  Google Scholar 

  19. Grootendorst P, Marshall D, Pericak D, Bellamy N, Feeny D, Torrance GW. A model to estimate health utilities index mark 3 utility scores from WOMAC index scores in patients with osteoarthritis of the knee. J Rheumatol. 2007;34:534–42.

    PubMed  Google Scholar 

  20. Horsman J, Furlong W, Feeny D, Torrance G. The Health Utilities Index (HUI): concepts, measurement properties and applications. Health Qual Life Outcomes. 2003;1:54.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Devlin NJ, Brooks R. EQ-5D and the EuroQol Group: past, present and future. Appl Health Econ Health Policy. 2017;15:127–37.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Consumer Prices (MEI). http://stats.oecd.org/Index.aspx?DatasetCode=MEI_PRICES. Accessed 13 Apr 2015.

  23. Fagnani F, Bouvenot G, Valat JP, Bardin T, Berdah L, Lafuma A, et al. Medico-economic analysis of diacerein with or without standard therapy in the treatment of osteoarthritis. Pharmacoeconomics. 1998;13:135–46.

    Article  CAS  PubMed  Google Scholar 

  24. Bruyère O, Scholtissen S, Neuprez A, Hiligsmann M, Toukouki A, Reginster JY. Impact of chondroitin sulphate on health utility in patients with knee osteoarthritis: towards economic analysis. J Med Econ. 2009;12:356–60.

    Article  PubMed  Google Scholar 

  25. Scholtissen S, Bruyère O, Neuprez A, Severens JL, Herrero-Beaumont G, Rovati L, et al. Glucosamine sulphate in the treatment of knee osteoarthritis: cost-effectiveness comparison with paracetamol. Int J Clin Pract. 2010;64:756–62.

    Article  CAS  PubMed  Google Scholar 

  26. Losina E, Daigle ME, Suter LG, Hunter DJ, Solomon DH, Walensky RP, et al. Disease-modifying drugs for knee osteoarthritis: can they be cost-effective? Osteoarthr Cartil. 2013;21:655–67.

    Article  CAS  Google Scholar 

  27. Torrance GW, Raynauld JP, Walker V, Goldsmith CH, Bellamy N, Band PA, et al. A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 2 of 2): economic results. Osteoarthr Cartil. 2002;10:518–27.

    Article  CAS  Google Scholar 

  28. Yen Z-S, Lai M-S, Wang C-T, Chen L-S, Chen S-C, Chen W-J, et al. Cost-effectiveness of treatment strategies for osteoarthritis of the knee in Taiwan. J Rheumatol. 2004;31:1797–803.

    PubMed  Google Scholar 

  29. Chou C-W, Lue K-H, Lee H-S, Lin R-C, Lu K-H. Hylan G-F 20 has better pain relief and cost-effectiveness than sodium hyaluronate in treating early osteoarthritic knees in Taiwan. J Formos Med Assoc. 2009;108:663–72.

    Article  CAS  PubMed  Google Scholar 

  30. Hatoum HT, Fierlinger AL, Lin S-J, Altman RD. Cost-effectiveness analysis of intra-articular injections of a high molecular weight bioengineered hyaluronic acid for the treatment of osteoarthritis knee pain. J Med Econ. 2014;17:326–37.

    Article  PubMed  Google Scholar 

  31. Castro J-C, Daza A-M, Misas J-D. Cost-effectiveness analysis of viscosupplementation versus conventional supportive therapy for knee osteoarthritis in Colombia. Value Health Reg Issues. 2015;8:56–61.

    Article  PubMed  Google Scholar 

  32. Rosen J, Sancheti P, Fierlinger A, Niazi F, Johal H, Bedi A. Cost-effectiveness of different forms of intra-articular injections for the treatment of osteoarthritis of the knee. Adv Ther. 2016;33:998–1011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hermans J, Reijman M, Goossens LMA, Verburg H, Bierma-Zeinstra SMA, Koopmanschap MA. Cost-utility analysis of high molecular weight hyaluronic acid for knee osteoarthritis in everyday clinical care in patients at a working age: an economic evaluation of a randomized clinical trial. Arthritis Care Res. 2018;70:89–97.

    Article  CAS  Google Scholar 

  34. Kahan A, Lleu P-L, Salin L. Prospective randomized study comparing the medicoeconomic benefits of Hylan GF-20 vs. conventional treatment in knee osteoarthritis. Joint Bone Spine. 2003;70:276–81.

    Article  PubMed  Google Scholar 

  35. Thomas T, Amouroux F, Vincent P. Intra articular hyaluronic acid in the management of knee osteoarthritis: pharmaco-economic study from the perspective of the national health insurance system. PLoS One. 2017;12:e0173683.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Miller LE, Block JE. An 8-week knee osteoarthritis treatment program of hyaluronic acid injection, deliberate physical rehabilitation, and patient education is cost effective at 2 years follow-up: the OsteoArthritis Centers of AmericaSM experience. Clin Med Insights Arthritis Musculoskelet Disord. 2014;7:49–55.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Mazières B, Bard H, Ligier M, Bru I, d’Orsay GG, Le Pen C. Medicoeconomic evaluation of hyaluronic acid for knee osteoarthritis in everyday practice: the MESSAGE study. Joint Bone Spine. 2007;74:453–60.

    Article  PubMed  Google Scholar 

  38. Altman R, Alarcón G, Appelrouth D, Bloch D, Borenstein D, Brandt K, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum. 1991;34:505–14.

    Article  CAS  PubMed  Google Scholar 

  39. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29:1039–49.

    Article  CAS  PubMed  Google Scholar 

  40. Ramsey S, Willke R, Briggs A, Brown R, Buxton M, Chawla A, et al. Good research practices for cost-effectiveness analysis alongside clinical trials: the ISPOR RCT-CEA task force report. Value Health. 2005;8:521–33.

    Article  PubMed  Google Scholar 

  41. Ramsey SD, Willke RJ, Glick H, Reed SD, Augustovski F, Jonsson B, et al. Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report. Value Health. 2015;18:161–72.

    Article  PubMed  Google Scholar 

  42. Hiligsmann M, Cooper C, Guillemin F, Hochberg MC, Tugwell P, Arden N, et al. A reference case for economic evaluations in osteoarthritis: an expert consensus article from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum. 2014;44:271–82.

    Article  PubMed  Google Scholar 

  43. Hawkins N, Scott DA. Cost-effectiveness analysis: discount the placebo at your peril. Med Decis Making. 2010;30:536–43.

    Article  PubMed  Google Scholar 

  44. Polimeni JM, Vichansavakul K, Iorgulescu RI, Chandrasekara R. Why perspective matters In health outcomes research analyses. Int Bus Econ Res J. 2013;12(11):1503–12.

    Google Scholar 

  45. Massetti M, Aballéa S, Videau Y, Rémuzat C, Roïz J, Toumi M. A comparison of HAS & NICE guidelines for the economic evaluation of health technologies in the context of their respective national health care systems and cultural environments. J Mark Access Health Policy. 2015;3:24966.

    Article  Google Scholar 

  46. Reginster J-Y. The efficacy of glucosamine sulfate in osteoarthritis: financial and nonfinancial conflict of interest. Arthritis Rheum. 2007;56:2105–10.

    Article  CAS  PubMed  Google Scholar 

  47. Laterre P-F, François B. Strengths and limitations of industry vs. academic randomized controlled trials. Clin Microbiol Infect. 2015;21:906–9.

    Article  PubMed  Google Scholar 

  48. Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum Z, et al. The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation. Health Technol Assess. 2009;13:1–148.

    Article  CAS  PubMed  Google Scholar 

  49. Waddell DD. Viscosupplementation with hyaluronans for osteoarthritis of the knee: clinical efficacy and economic implications. Drugs Aging. 2007;24:629–42.

    Article  CAS  PubMed  Google Scholar 

  50. Dagenais S. Intra-articular hyaluronic acid (viscosupplementation) for knee osteoarthritis. Issues Emerg Health Technol. 2006;94:1–4.

    Google Scholar 

  51. Cooper C, Rannou F, Richette P, Bruyère O, Al-Daghri N, Altman RD, et al. Use of intraarticular hyaluronic acid in the management of knee osteoarthritis in clinical practice. Arthritis Care Res. 2017;69:1287–96.

    Article  Google Scholar 

  52. Guillemin F, Rat AC, Mazieres B, Pouchot J, Fautrel B, Euller-Ziegler L, et al. Prevalence of symptomatic hip and knee osteoarthritis: a two-phase population-based survey. Osteoarthr Cartil. 2011;19:1314–22.

    Article  CAS  Google Scholar 

  53. Salmon JH, Rat AC, Sellam J, Michel M, Eschard JP, Guillemin F, et al. Economic impact of lower-limb osteoarthritis worldwide: a systematic review of cost-of-illness studies. Osteoarthr Cartil. 2016;24:1500–8.

    Article  CAS  Google Scholar 

  54. Bijlsma JWJ, Berenbaum F, Lafeber FPJG. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377:2115–26.

    Article  PubMed  Google Scholar 

  55. Courties A, Gualillo O, Berenbaum F, Sellam J. Metabolic stress-induced joint inflammation and osteoarthritis. Osteoarthr Cartil. 2015;23:1955–65.

    Article  CAS  Google Scholar 

  56. Richmond SA, Fukuchi RK, Ezzat A, Schneider K, Schneider G, Emery CA. Are joint injury, sport activity, physical activity, obesity, or occupational activities predictors for osteoarthritis? A systematic review. J Orthop Sports Phys Ther. 2013;43:515–9.

    Article  PubMed  Google Scholar 

  57. Hiligsmann M, Cooper C, Arden N, Boers M, Branco JC, Luisa Brandi M, et al. Health economics in the field of osteoarthritis: an expert’s consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum. 2013;43:303–13.

    Article  PubMed  Google Scholar 

  58. National Institute for Health and Care Excellence. Guide to the methods of technology appraisal 2013. London: National Institute for Health and Care Excellence (NICE); 2013. http://www.ncbi.nlm.nih.gov/books/NBK395867/. Accessed 8 Feb 2018.

  59. Thokala P, Ochalek J, Leech AA, Tong T. Cost-effectiveness thresholds: the past, the present and the future. Pharmacoeconomics. 2018;36(5):509–22.

    Article  PubMed  Google Scholar 

  60. Rawlins MD, Culyer AJ. National institute for clinical excellence and its value judgments. BMJ. 2004;329:224–7.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Gafni A, Birch S. Incremental cost-effectiveness ratios (ICERs): the silence of the lambda. Soc Sci Med. 1982;2006(62):2091–100.

    Google Scholar 

  62. Cleemput I, Neyt M, Thiry N, De Laet C, Leys M. Using threshold values for cost per quality-adjusted life-year gained in healthcare decisions. Int J Technol Assess Health Care. 2011;27:71–6.

    Article  PubMed  Google Scholar 

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Correspondence to Jean-Hugues Salmon.

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Data Availability Statement

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Conflict of Interest

Author disclosures of honoraria for advice or public speaking, grants received and/or advisory board participation are as follows: Jean Hugues Salmon has received consultancy fees from Abbvie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB. Isabelle Charlot-Lambrecht has received consultancy fees from Amgen and MSD. Jean-Paul Eschard has received consultancy fees from Abbvie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and UCB. Bruno Fautrel has received research grants from AbbVie, Lilly, MSD and Pfizer, and consultancy fees from AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, SOBI and UCB. Anne-Christine Rat and Damien Jolly declare no conflicts of interest.

Funding

No funding was received for this systematic review.

Author Contributions

The design of the study was conceived by JHS, BF and DJ. Data collection, management and analysis were performed by JHS and BF. All authors participated in the interpretation of the results and manuscript writing. All authors have read and approved the final version of the manuscript for publication.

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Salmon, JH., Rat, AC., Charlot-Lambrecht, I. et al. Cost Effectiveness of Intra-Articular Hyaluronic Acid and Disease-Modifying Drugs in Knee Osteoarthritis. PharmacoEconomics 36, 1321–1331 (2018). https://doi.org/10.1007/s40273-018-0695-5

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