Knee Osteoarthritis Pain Management with an Innovative High and Low Molecular Weight Hyaluronic Acid Formulation (HA-HL): A Randomized Clinical Trial

Migliore, A.; Blicharski, T.; Plebanski, R.; Zegota, Z.; Gyula, G.; Rannou, F.; Reginster, Jean-Yves

doi:10.1007/s40744-021-00363-3

Article (Scientific journals)

Knee Osteoarthritis Pain Management with an Innovative High and Low Molecular Weight Hyaluronic Acid Formulation (HA-HL): A Randomized Clinical Trial

Migliore, A.; Blicharski, T.; Plebanski, R. et al.

2021 • In Rheumatology and Therapy, 8 (4), p. 1617-1636

Peer Reviewed verified by ORBi

Permalink
https://hdl.handle.net/2268/268032

DOI
10.1007/s40744-021-00363-3

Files (1)Send to Details Statistics Bibliography Similar publications

Files

Full Text

knee osteoarthritis pain management with an innovative high and low molecular weight hyaluronic acid formulation - a randomized clinical trial.pdf

Publisher postprint (1.47 MB)

Download

All documents in ORBi are protected by a user license.

Send to

RIS BibTex APA Chicago Permalink X Linkedin

Details

Keywords :

High and low molecular weight hyaluronic (HA-HL); Hyaluronic acid; Intra-articular; Knee; Osteoarthritis; Treatment

Abstract :

[en] Introduction: The objective of this study was to compare a single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) versus placebo in treating moderate-to-severe symptomatic knee osteoarthritis. Methods: Subjects with primary osteoarthritis knee pain (Kellgren and Lawrence grade 2–3) were randomly assigned to intra-articular HA-HL or placebo in a prospective, double-blind, 24-week study. The primary outcome variable was change from screening to week 24 of a Visual Analogue Scale (VAS) pain score. Secondary outcomes included Lequesne’s algofunctional index, EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) response and rescue medication usage. Results: In a total of 692 randomized patients, a rapid decrease was observed in mean VAS pain score from baseline to week 1 (26 ± 24 mm in the HA-HL group vs. 23 ± 23 mm in the placebo group); pain intensity continued to decrease during 24 weeks of follow-up, reaching a mean change from baseline of 35 ± 28 mm vs. 32 ± 27 mm at week 24. Mixed model analysis demonstrated statistically significant differences between groups in favor of the HA-HL group at weeks 1, 6, 12, and 24. HA-HL was also more effective than placebo in improving Lequesne’s algofunctional index, OMERACT-OARSI response, and health-related quality of life. The use of rescue medication (paracetamol 500 mg tablets; ≤ 6 per day) was lower in the HA-HL group. Both treatments were similarly well tolerated. Conclusions: A single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) is effective in providing fast, sustained, and clinically relevant reductions in pain, functional limitation, and health-related quality of life that were apparent at 1 week after the intra-articular injection and maintained throughout the 24-week follow-up in subjects with painful knee osteoarthritis, with a good safety profile. Trial Registration: ClinicalTrials.gov identifier: NCT03200288. © 2021, The Author(s).

Disciplines :

General & internal medicine

Author, co-author :

Migliore, A.; Rheumatology Unit, S. Pietro FBF Hospital, Via Cassia 600, Rome, 00189, Italy

Blicharski, T.; Chair and Department of Rehabilitation and Orthopaedics, Medical University of Lublin, Lublin, Poland

Plebanski, R.; Klinika Zdrowej Kości, Lodz, Poland

Zegota, Z.; SOLB, Zbigniew Zegota, Ostroda, Poland

Gyula, G.; Swan Med Hungary Kft, Létavértes, Hungary

Rannou, F.; Faculté de Médecine Paris Descartes, Université de Paris, Sorbonne Paris Cité, Paris, 75006, France, AP-HP, Hôpitaux Universitaires Paris Centre-Groupe Hospitalier Cochin, Service de Rééducation et de Réadaptation de l’Appareil Locomoteur et des Pathologies du Rachis, Paris, 75014, France, INSERM UMR 1124, Laboratoire de Toxicité Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire (T3S), Faculté des Sciences Fondamentales et Biomédicales, Université de Paris, Sorbonne Paris Cité, Paris, 75006, France

Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé

Language :

English

Title :

Knee Osteoarthritis Pain Management with an Innovative High and Low Molecular Weight Hyaluronic Acid Formulation (HA-HL): A Randomized Clinical Trial

Publication date :

2021

Journal title :

Rheumatology and Therapy

ISSN :

2198-6576

eISSN :

2198-6584

Publisher :

Adis

Volume :

Issue :

Pages :

1617-1636

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

ISO 14155; Eli Lilly and Company; Pfizer; Novartis; Roche; Sanofi; Teva Pharmaceutical Industries; Fondation Arthritis; Horizon 2020 Framework Programme, H2020; Cilag; Radius Health; Agence Nationale de la Recherche, ANR

Available on ORBi :

since 09 February 2022

Statistics

Number of views

91 (5 by ULiège)

Number of downloads

70 (3 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745–59.
Mobasheri A, Batt M. An update on the pathophysiology of osteoarthritis. Ann Phys Rehabil Med. 2016;59(5–6):333–9.
Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthri Cartil. 2019;27(11):1578–89.
Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323–30.
Altman RD. Pharmacological therapies for osteoarthritis of the hand: a review of the evidence. Drugs Aging. 2010;27(9):729–45.
Bruyere O, Cooper C, Arden N, et al. Can we identify patients with high risk of osteoarthritis progression who will respond to treatment? A focus on epidemiology and phenotype of osteoarthritis. Drugs Aging. 2015;32(3):179–87.
Cooper C, Rannou F, Richette P, et al. Use of intraarticular hyaluronic acid in the management of knee osteoarthritis in clinical practice. Arthritis Care Res (Hoboken). 2017;69(9):1287–96.
Maheu E, Bannuru RR, Herrero-Beaumont G, et al. Why we should definitely include intra-articular hyaluronic acid as a therapeutic option in the management of knee osteoarthritis: Results of an extensive critical literature review. Semin Arthritis Rheum. 2019;48(4):563–72.
Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.
Raman R, Henrotin Y, Chevalier X, et al. Decision algorithms for the retreatment with viscosupplementation in patients suffering from knee osteoarthritis: Recommendations from the EUROpean VIScosupplementation COnsensus Group (EUROVISCO). Cartilage. 2018;9(3):263–75.
Bruyere O, Cooper C, Pelletier JP, et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum. 2014;44(3):253–63.
Fernandes L, Hagen KB, Bijlsma JW, et al. EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Ann Rheum Dis. 2013;72(7):1125–35.
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 Res (Hoboken). 2012;64(4):465–74.
Jordan KM, Arden NK, Doherty M, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62(12):1145–55.
Rillo O, Riera H, Acosta C, et al. PANLAR consensus recommendations for the management in osteoarthritis of hand, hip, and knee. J Clin Rheumatol. 2016;22(7):345–54.
Ariani A, Manara M, Fioravanti A, et al. The Italian Society for Rheumatology clinical practice guidelines for the diagnosis and management of knee, hip and hand osteoarthritis. Reumatismo. 2019;71(S1):5–21.
Bruyere O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019;49(3):337–50.
Papalia R, Zampogna B, Russo F, et al. Comparing hybrid hyaluronic acid with PRP in end career athletes with degenerative cartilage lesions of the knee. J Biol Regul Homeost Agents. 2016;30(4 Suppl 1):17–23.
US Department of Health and Human Services, U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH). Guidance for Industry Clinical Development Programs for Drugs, Devices, and Biological Products Intended for the Treatment of Osteoarthritis (OA). Draft Guidance. US Food and Drug Administration; 1999.
Committee for Medicinal Products for Human Use (CHMP). Guideline on Clinical Investigation of Medicinal Products Used in the Treatment of Osteoarthritis (CPMP/EWP/784/97 Rev 1). London: European Medicines Agency; 2010.
Group for the Respect Of Ethics and Excellence in Science (GREES): Osteoarthritis Section. Recommendations for the registration of drugs used in the treatment of osteoarthritis. Ann Rheum Dis. 1996;55(8):552–7.
McAlindon TE, Driban JB, Henrotin Y, et al. OARSI clinical trials recommendations: design, conduct, and reporting of clinical trials for knee osteoarthritis. Osteoarthr Cartil. 2015;23(5):747–60.
Jordan JM, Henrotin Y. Osteoarthritis Research Society international initiative on recommendations for conducting clinical trials in osteoarthritis: overview. Osteoarthr Cartil. 2015;23(5):671–3.
Altman R, Brandt K, Hochberg M, et al. Design and conduct of clinical trials in patients with osteoarthritis: recommendations from a task force of the Osteoarthritis Research Society. Results from a workshop. Osteoarthr Cartil. 1996;4(4):217–43.
Dougados M, Devogelaer J-P, Annefeld M, et al. Recommendations for the registration of drugs used in the treatment of osteoarthritis. Ann Rheum Dis. 1996;55:552–7.
McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 2014;22(3):363–88.
Reginster JY, Reiter-Niesert S, Bruyere O, et al. Recommendations for an update of the 2010 European regulatory guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement. Osteoarthr Cartil. 2015;23(12):2086–93.
Strand V, Kelman A. Outcome measures in osteoarthritis: randomized controlled trials. Curr Rheumatol Rep. 2004;6(1):20–30.
Kirchner M, Marshall D. A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee. Osteoar Cartil. 2006;14(2):154–62.
Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16(4):494–502.
Pham T, van der Heijde D, Altman RD, et al. OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthr Cartil. 2004;12(5):389–99.
Papalia R, Russo F, Torre G, et al. Hybrid hyaluronic acid versus high molecular weight hyaluronic acid for the treatment of osteoarthritis in obese patients. J Biol Regul Homeost Agents. 2017;31(4 Suppl 2):103–9.
Manciameli A. Trattamento della gonartrosi moderata mediante iniezione intrarticolare di acido ialuronico sale sodico [Italian]. Giornale Ital Ortop Traumatol. 2018;44:146–9.
Abate M, Salini V. Efficacy and safety study on a new compound associating low and high molecular weight hyaluronic acid in the treatment of hip osteoarthritis. Int J Immunopathol Pharmacol. 2017;30(1):89–93.
Tenti S, Pascarelli NA, Giannotti S, et al. Can hybrid hyaluronic acid represent a valid approach to treat rizoarthrosis? A retrospective comparative study. BMC Musculoskelet Disord. 2017;18(1):444.
Bartoloni E, Luccioli F, La Paglia GMC, et al. Effect of Sinovial High-Low® injections in trapeziometacarpal osteoarthritis. Clin Exp Rheumatol. 2019;37(1):166.
Dworkin RH, Turk DC, McDermott MP, et al. Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations. Pain. 2009;146(3):238–44.
Moore RA, Moore OA, Derry S, McQuay HJ. Numbers needed to treat calculated from responder rates give a better indication of efficacy in osteoarthritis trials than mean pain scores. Arthritis Res Ther. 2008;10(2):R39.
Altman R, Lim S, Steen RG, Dasa V. Hyaluronic acid injections are associated with delay of total knee replacement surgery in patients with knee osteoarthritis: evidence from a large U.S. health claims database. PLoS ONE. 2015;10(12):e0145776.
Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008;67(12):1716–23.
Saltzman BM, Leroux T, Meyer MA, et al. The therapeutic effect of intra-articular normal saline injections for knee osteoarthritis: a meta-analysis of evidence level 1 studies. Am J Sports Med. 2017;45(11):2647–53.
Bar-Or D, Rael LT, Brody EN. Use of saline as a placebo in intra-articular injections in osteoarthritis: potential contributions to nociceptive pain relief. Open Rheumatol J. 2017;11:16–22.
Altman RD, Devji T, Bhandari M, et al. Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: a systematic review and meta-analysis of randomized trials. Semin Arthritis Rheum. 2016;46(2):151–9.
Migliore A, Bizzi E, Herrero-Beaumont J, et al. The discrepancy between recommendations and clinical practice for viscosupplementation in osteoarthritis: mind the gap! Eur Rev Med Pharmacol Sci. 2015;19(7):1124–9.
Beaudart C, Lengele L, Leclercq V, et al. Symptomatic efficacy of pharmacological treatments for knee osteoarthritis: a systematic review and a network meta-analysis with a 6-month time horizon. Drugs. 2020;80(18):1947–59.
de Wit M, Cooper C, Tugwell P, et al. Practical guidance for engaging patients in health research, treatment guidelines and regulatory processes: results of an expert group meeting organized by the World Health Organization (WHO) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Aging Clin Exp Res. 2019;31(7):905–15.
Conrozier T, Monet M, Lohse A, Raman R. Getting better or getting well? The Patient Acceptable Symptom State (PASS) better predicts patient’s satisfaction than the decrease of pain, in knee osteoarthritis subjects treated with viscosupplementation. Cartilage. 2018;9(4):370–7.