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Safety and efficacy of bi-annual intra-articular LBSA0103 injections in patients with knee osteoarthritis

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Abstract

The objective of this study is to assess the safety and efficacy of repeated intra-articular injection of high molecular weight hyaluronic acid (LBSA0103) at a 26-week interval, in patients with osteoarthritis of the knee. The study was an open-label, single arm, multicentre prospective trial conducted in patients with symptomatic knee osteoarthritis. The intervention consisted of two intra-articular injections of LBSA0103, with the second injection performed 26 weeks after the first injection. The primary outcome was the incidence of adverse drug reactions related to each injection. Assessment of efficacy of repeated injections in terms of maintenance of pain relief was a secondary objective of this study. Of the 185 patients screened, 174 patients received the first injection and 153 patients received both injections of LBSA0103. Nine adverse drug reactions occurred in seven patients (4.02%) after the first injection, while only one adverse drug reaction occurred (0.65%) after the second injection. As a secondary outcome measure, the improvements in the efficacy parameters including total WOMAC score and weight-bearing pain were all significant at both week 13 and 39 compared to the baseline value (P < 0.001), and improvements after the second injection were consistent with those after the initial injection of LBSA0103 (between week 26 and week 39, P < 0.001). Repeated intra-articular injection of LBSA0103 at a 26-week interval is safe without increased risk of adverse drug reactions. Additionally, LBSA0103 is effective in reduction of osteoarthritis knee pain and in maintenance of pain reduction for a 39-week period when a second injection is administered.

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References

  1. Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE (2011) Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis–meta-analysis. Osteoarthr Cartil 19(6):611–619

    Article  CAS  PubMed  Google Scholar 

  2. Bannuru RR, Natov NS, Obadan IE, Price LL, Schmid CH, McAlindon TE (2009) Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum 61(12):1704–1711

    Article  CAS  PubMed  Google Scholar 

  3. Lo GH, LaValley M, McAlindon T, Felson DT (2003) Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA 290(23):3115–3121

    Article  CAS  PubMed  Google Scholar 

  4. Modawal A, Ferrer M, Choi HK, Castle JA (2005) Hyaluronic acid injections relieve knee pain. J Fam Pract 54(9):758–767

    PubMed  Google Scholar 

  5. Strauss EJ, Hart JA, Miller MD, Altman RD, Rosen JE (2009) Hyaluronic acid viscosupplementation and osteoarthritis: current uses and future directions. Am J Sports Med 37(8):1636–1644

    Article  PubMed  Google Scholar 

  6. Greenberg DD, Stoker A, Kane S, Cockrell M, Cook JL (2006) Biochemical effects of two different hyaluronic acid products in a co-culture model of osteoarthritis. Osteoarthr Cartil 14(8):814–822

    Article  CAS  PubMed  Google Scholar 

  7. Karna E, Miltyk W, Palka JA, Jarzabek K, Wolczynski S (2006) Hyaluronic acid counteracts interleukin-1-induced inhibition of collagen biosynthesis in cultured human chondrocytes. Pharmacol Res 54(4):275–281

    Article  CAS  PubMed  Google Scholar 

  8. Hunter DJ (2015) Viscosupplementation for osteoarthritis of the knee. N Engl J Med 372(11):1040–1047

    Article  CAS  PubMed  Google Scholar 

  9. Gomis A, Pawlak M, Balazs EA, Schmidt RF, Belmonte C (2004) Effects of different molecular weight elastoviscous hyaluronan solutions on articular nociceptive afferents. Arthritis Rheum 50(1):314–326

    Article  CAS  PubMed  Google Scholar 

  10. Navarro-Sarabia F, Coronel P, Collantes E et al (2011) A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project. Ann Rheum Dis 70(11):1957–1962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chevalier X, Jerosch J, Goupille P et al (2010) Single, intra-articular treatment with 6 ml hylan GF 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis 69(01):113–119

    Article  CAS  PubMed  Google Scholar 

  12. Åkermark C, Berg P, Björkman A, Malm P (2002) Non-animal stabilised hyaluronic acid in the treatment of osteoarthritis of the knee. Clin Drug Investig 22(3):157–166

    Article  Google Scholar 

  13. Kenne L, Gohil S, Nilsson EM et al (2013) Modification and cross-linking parameters in hyaluronic acid hydrogels—definitions and analytical methods. Carbohyd Polym 91(1):410–418

    Article  CAS  Google Scholar 

  14. Boulle K, Glogau R, Kono T et al (2013) A review of the metabolism of 1, 4-butanediol diglycidyl ether-crosslinked hyaluronic acid dermal fillers. Dermatol Surg 39(12):1758–1766

    Article  PubMed  PubMed Central  Google Scholar 

  15. Altman R, Asch E, Bloch D et al (1986) Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum 29(8):1039–1049

    Article  CAS  PubMed  Google Scholar 

  16. Kellgren J, Lawrence J (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16(4):494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jüni P, Hari R, Rutjes AW (2015) Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev 22(10):CD005328

    Google Scholar 

  18. Fauci AS, Dale DC, Balow JE (1976) Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 84(3):304–315

    Article  CAS  PubMed  Google Scholar 

  19. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) 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 15(12):1833–1840

    CAS  PubMed  Google Scholar 

  20. Pham T, van der Heijde D, Altman R et al (2004) OMERACT-OARSI initiative: osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthr Cartil 12(5):389–399

    Article  CAS  PubMed  Google Scholar 

  21. Berenbaum F, Grifka J, Cazzaniga S et al (2012) A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis. Ann Rheum Dis 71(9):1454–1460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Larsen NE, Dursema H, Skrabut EM (2007) Clearance kinetics of a single injection crosslinked hylan-based viscosupplement in a rabbit model. Osteoarthr Cartil 15:C64

    Article  Google Scholar 

  23. Pullman-Mooar S, Mooar P, Sieck M, Clayburne G, Schumacher HR (2002) Are there distinctive inflammatory flares after hylan gf 20 intraarticular injections? J Rheumatol 29(12):2611–2614

    CAS  PubMed  Google Scholar 

  24. Goldberg VM, Coutts RD (2004) Pseudoseptic reactions to hylan viscosupplementation: diagnosis and treatment. Clin Orthop Relat Res 419:130–137

    Article  Google Scholar 

  25. Leopold SS, Warme WJ, Pettis PD, Shott S (2002) Increased frequency of acute local reaction to intra-articular hylan GF-20 (synvisc) in patients receiving more than one course of treatment. J Bone Jt Surg Am 84(9):1619–1623

    Article  Google Scholar 

  26. Zhang W, Robertson J, Jones A, Dieppe P, Doherty M (2008) The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis 67(12):1716–1723

    Article  CAS  PubMed  Google Scholar 

  27. Campbell J, Bellamy N, Gee T (2007) Differences between systematic reviews/meta-analyses of hyaluronic acid/hyaluronan/hylan in osteoarthritis of the knee. Osteoarthritis and cartilage 15(12):1424–1436

    Article  CAS  PubMed  Google Scholar 

  28. McAlindon TE, Bannuru RR (2012) Osteoarthritis: is viscosupplementation really so unsafe for knee OA? Nat Rev Rheumatol 8(11):635–636

    Article  PubMed  Google Scholar 

  29. Jørgensen A, Stengaard-Pedersen K, Simonsen O et al (2010) 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. doi:10.1136/ard.2009.118042

    Google Scholar 

  30. Maheu E, Zaim M, Appelboom T et al (2010) Comparative efficacy and safety of two different molecular weight (MW) hyaluronans F60027 and Hylan G-F20 in symptomatic osteoarthritis of the knee (KOA). Results of a non inferiority, prospective, randomized, controlled trial. Clin Exp Rheumatol 29(3):527–535

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea

    Jin Kyu Lee

  2. Department of Orthopedic Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

    Chong-Hyuk Choi

  3. Department of Orthopedic Surgery, KonKuk University Medical Center, KonKuk University School of Medicine, Seoul, Republic of Korea

    Kwang-Jun Oh

  4. Department of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Hee-Soo Kyung

  5. Department of Orthopedic Surgery, National Health Insurance Corporation Ilsan Hospital, Goyang, Republic of Korea

    Ju-Hyung Yoo

  6. Department of Orthopedic Surgery, Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Chul-Won Ha

  7. Department of Orthopedic Surgery, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Republic of Korea

    Seong-Il Bin

  8. Department of Orthopedic Surgery, Seoul National University Boramae Medical Center, Seoul, Republic of Korea

    Seung-Baik Kang

  9. Department of Orthopedic Surgery, Inha University Hospital, Incheon, Republic of Korea

    Myung Ku Kim

  10. Department of Orthopedic Surgery, Chonbuk National University Hospital, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea

    Ju-Hong Lee

  11. Department of Orthopedic Surgery, Seoul National University College of Medicine, 101 Daehangno, Jongnogu, Seoul, 03080, Republic of Korea

    Myung Chul Lee

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  1. Jin Kyu Lee
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Correspondence to Myung Chul Lee.

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Disclosure

All authors have no financial interests or personal relationships with people or organization that could have potentially and inappropriately influence the conduct or reporting of this work.

Ethics statement for human study

The institutional review board (IRB) of each hospital granted approval of the trial, and written consent approved by the Ministry of Food and Drug Safety in Korea as well as the IRB was obtained from each patient before initiation of the study.

Ethics statement for clinical trials

This is a clinical trial on the third phase, registered at the service of the US National Institutes of Health (ClinicalTrials.gov; http://www.clinicaltrials.gov), number NCT02122601.

Funding

This study was funded by LG Life Sciences. The funding sources had no role in the study design, collection, analysis or interpretation of the data, writing of the manuscript, or in the decision to submit the manuscript for publication.

Conflict of interest

All authors declare that they have no conflict of interest.

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Lee, J.K., Choi, CH., Oh, KJ. et al. Safety and efficacy of bi-annual intra-articular LBSA0103 injections in patients with knee osteoarthritis. Rheumatol Int 37, 1807–1815 (2017). https://doi.org/10.1007/s00296-017-3803-5

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  • DOI: https://doi.org/10.1007/s00296-017-3803-5

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