Advertisement

Clinical Drug Investigation

, Volume 22, Issue 3, pp 157–166 | Cite as

Non-Animal Stabilised Hyaluronic Acid in the Treatment of Osteoarthritis of the Knee

A Tolerability Study
  • Christian Åkermark
  • Per Berg
  • Anders Björkman
  • Per Malm
Original Research Article

Abstract

Objective: To evaluate the safety of an intra-articular injection of non-animal stabilised hyaluronic acid (NASHA) in patients with osteoarthritis (OA) of the knee.

Design and setting: Non-blind prospective study conducted at five centres in Sweden.

Patients and participants: 103 patients aged at least 50 years with OA of the knee (128 knees).

Methods: A single intra-articular injection of NASHA (60mg/3ml) was administered, and patients were followed up for 3 months. In an extension to the study, 53 patients (72 knees) who had participated in the first study received a second intra-articular injection of NASHA (60mg/3ml) approximately 6 months after the first injection. Patients in the study extension were followed up over a 1-month period.

Outcome measures: The primary outcome measure in both the primary study and the study extension was the frequency of device-related, unanticipated adverse events. Anticipated adverse events were defined as local reactions such as transient knee pain, swelling, tenderness and heat sensation at the injection site during the first 3 weeks after injection. The following efficacy criteria were also measured: knee pain [measured with a visual analogue scale (VAS)], knee swelling and tenderness, patient’s overall disease condition, and overall treatment satisfaction.

Results: After the first injection, 51 local reactions that were possibly related to the study product or injection procedure were reported. Of these, seven events, all described as knee pain and swelling, fulfilled the definition of device-related, unanticipated adverse events, giving an event frequency of 5% in 128 injections. Following the second injection, 11 events were considered potentially related to the study product or the injection procedure, of which three were classed as device-related, unanticipated adverse events, giving an event frequency of 4% in 72 injections. A statistically significant reduction in knee pain (p < 0.0001) was seen after both injections, and tenderness to palpation was significantly reduced at 3 months after the first injection compared with baseline (p = 0.0003). The proportion of knees with swelling was unchanged after either injection. No significant change in patient’s assessment of overall disease condition was noted following either injection, although the physician’s assessment indicated a trend towards a reduction in overall disease condition after the first injection. A clear majority of patients (80%, 76/95) regarded their overall satisfaction with treatment to be very good/good or fair after the first injection.

Conclusions: No safety concerns were raised in either the primary study or in the study extension. NASHA as an intra-articular therapy for OA of the knee appears to have an acceptable safety profile and thus merits further investigation regarding its long-term clinical efficacy.

Keywords

Hyaluronic Acid Knee Pain Visual Analogue Scale Score Local Reaction Study Product 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This study was supported by a financial grant from Q-Med AB, Uppsala, Sweden.

The fifth participating centre was Ortopedkliniken, Östersunds, Sjukhus, Östersund, Sweden, under the guidance of Dr Börje Samuelsson.

References

  1. 1.
    Kramer JS, Yelin EH, Epstein WV. Social and economic impacts of four musculoskeletal conditions. Arthritis Rheum 1983; 26: 901–7PubMedCrossRefGoogle Scholar
  2. 2.
    Cunningham LS, Kelsey JL. Epidemiology of musculoskeletal impairments and associated disability. Am J Public Health 1984; 74: 574–9PubMedCrossRefGoogle Scholar
  3. 3.
    Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998; 41: 778–99PubMedCrossRefGoogle Scholar
  4. 4.
    Murray CJL, Lopez AD. The global burden of disease. Geneva: World Health Organization, 1997Google Scholar
  5. 5.
    Spector TD, Hart DJ. How serious is knee osteoarthritis? Ann Rheum Dis 1992; 51: 1105–6PubMedCrossRefGoogle Scholar
  6. 6.
    Huskisson EC, Dieppe PA, Tucker AK, et al. Another look at osteoarthritis. Ann Rheum Dis 1979; 38: 423–42PubMedCrossRefGoogle Scholar
  7. 7.
    Bjelle A. Epidemiological aspects of osteoarthritis —an interview survey of the Swedish population and a review of previous studies. Scand J Rheumatol 1982; Suppl 43: 35–48Google Scholar
  8. 8.
    American College of Rheumatology Subcommittee on Arthritis. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum 2000; 43: 1905–15CrossRefGoogle Scholar
  9. 9.
    Roth, SH, Bennett RE. Nonsteroidal anti-inflammatory drug gastropathy. Arch Intern Med 1987; 147: 2093–100PubMedCrossRefGoogle Scholar
  10. 10.
    Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of non-steroidal anti-inflammatory drugs. Ann Intern Med 1991; 115: 787–96PubMedGoogle Scholar
  11. 11.
    Halls J, Jensen KB, Grodum E, et al. Drug-related admissions to a department of medical gastroenterology. The role of selfmedicated and prescribed drugs. Scand J Gastroenterol 1991; 26: 174–80CrossRefGoogle Scholar
  12. 12.
    Inman WH. Non-steroidal anti-inflammatory drugs: assessment of risks. Eur J Rheumatol Inflamm 1987; 8: 71–85PubMedGoogle Scholar
  13. 13.
    Bloom BS. Direct medical costs of disease and gastrointestinal side-effects during treatment for arthritis. Am J Med 1988; 84: 20–4PubMedCrossRefGoogle Scholar
  14. 14.
    Griffin MR, Ray WA, Schaffnre W. Non-steroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Intern Med 1988; 109: 359–63PubMedGoogle Scholar
  15. 15.
    Gray RG, Tenenbaum J, Gottlieb NL. Local corticosteroid injection treatment in rheumatic disorders. Semin Arthritis Rheum 1981; 10: 231–54PubMedCrossRefGoogle Scholar
  16. 16.
    Hochberg MC, Altman RD, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Arthritis Rheum 1995; 38: 1541–6PubMedCrossRefGoogle Scholar
  17. 17.
    Abatangelo G, O’Regan M. Hyaluronan: biological role and function in articular joints. Eur J Rheumatol Inflamm 1995; 15: 9–15Google Scholar
  18. 18.
    Towheed TE, Hochberg MC. A systematic review of randomized controlled trials of pharmacological therapy in osteoarthritis of the knee, with an emphasis on trial methodology. Semin Arthritis Rheum 1997; 26: 755–70PubMedCrossRefGoogle Scholar
  19. 19.
    Lussier A, Cividino AA, MacFarlane CA, et al. Visco-supplementation with hylan for the treatment of osteoarthritis: findings from clinical practice in Canada. J Rheumatol 1996; 23: 1579–85PubMedGoogle Scholar
  20. 20.
    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. Ann Rheum Dis 1996; 55: 424–31PubMedCrossRefGoogle Scholar
  21. 21.
    Bragantini A, Cassini M, De Bastiani G, et al. Controlled single-blind trial of intraarticularly injected hyaluronic acid in osteoarthritis of the knee. Clin Trials J 1987; 24: 333–40Google Scholar
  22. 22.
    Dixon ASJ, Jacoby RK, Berry H, et al. Clinical trial of intraarticular injection of sodium hyaluronate in patients with osteoarthritis of the knee. Curr Med Res Opin 1988; 11: 205–13PubMedCrossRefGoogle Scholar
  23. 23.
    Dougados M, Nguyen M, Listrat V, et al. High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial. Osteoarthritis Cartilage 1993; 1: 97–103PubMedCrossRefGoogle Scholar
  24. 24.
    Adams ME. An analysis of clinical studies of the use of cross-linked hyaluroan, hylan, in the treatment of osteoarthritis. J Rheumatol 1993; 20: 16–8Google Scholar
  25. 25.
    Altman RD, Moskovitz R, Hyalagan Study Group. Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: randomised clinical trial. J Rheumatol 1998; 25: 2203–12PubMedGoogle Scholar
  26. 26.
    Puttick MPE, Wade JP, Chalmers A, et al. Acute local reactions after intra-articular hylan for osteoarthritis of the knee. J Rheumatol 1995; 22: 1311–4PubMedGoogle Scholar
  27. 27.
    Henderson EB, Smith EC, Pegley F, et al. Intra-articular injections of 750 kD hyaluronan in the treatment of osteoarthritis: a randomised single centre double-blind placebo controlled trial of 91 patients demonstrating lack of efficacy. Ann Rheum Dis 1994; 53: 529–34PubMedCrossRefGoogle Scholar
  28. 28.
    Peyron JG. Intra-articular hyaluronan injections in the treatment of osteoarthrosis: state of the art review. J Rheumatol. 1993; 20Suppl 39: 10–5Google Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Christian Åkermark
    • 1
  • Per Berg
    • 2
  • Anders Björkman
    • 3
  • Per Malm
    • 4
  1. 1.Ortopediska HusetStockholmSweden
  2. 2.Akademiska Sjukhuset OrtopedklinikenUppsalaSweden
  3. 3.Aros LäkarmottagningUppsalaSweden
  4. 4.Odensala HälsocentralÖstersundSweden

Personalised recommendations