Clinical efficiency and safety of innovative synovial fluid prosthesis in the treatment of gonarthritis

Introduction. Scientific discussions about ways to improve the effectiveness and safety of osteoarthritis (OA) therapy do not stop. The article discusses the most controversial issues of the problem and presents the results of a study on the use of sodium hyaluronate in gonarthrosis.
Aim. To compare the clinical efficacy, tolerability and safety of the use of synovial fluid substitute of domestic manufacture and symptomatic slow-acting drugs (SYSADOA) in patients with gonarthrosis.
Study design. Prospective, comparative, randomized, single center study. The duration of the study was 12 months.
Materials and methods. The study included 180 patients with gonarthrosis, randomized into three groups. Study group: 50 patients treated with Ripart® sodium hyaluronate solution intra-articularly. Comparison group: 30 patients treated with SYSADOA, intraarticular. Control group: 100 patients treated with SYSADOA intramuscularly.
Results. The most rapid and pronounced decrease in the VAS index was obtained during sodium hyaluronate therapy: by 31% at the 1st week, by 48% by the end of the 2nd week, with a maximum decrease by 49.1% by the 3rd month (p < 0.001). After 12 months, a lower level of the VAS index was observed: 32% lower than before the start of therapy (t = 47.23; p < 0.001). Comparable results were observed in this group in terms of the dynamics of the AUSCAN/WOMAC index. The effectiveness of therapy in the comparison and control groups was lower (p < 0.05). In addition, the use of sodium hyaluronate provided a significant reduction in the need for taking NSAIDs: 20 patients completely stopped taking NSAIDs (40%), 25 (50%) – they began to take NSAIDs less often or reduced the dose of drugs by 2 times, after 12 months they continued taking NSAIDs only 20% of patients in this group (p < 0.05).
Сonclusions. Thus, Ripart® demonstrated high efficiency in reducing pain, contributed to a significant reduction in the need for NSAIDs in patients with gonarthrosis, and has a good safety profile.

1. Портянникова О.О., Цвингер С.М., Говорин А.В., Романова Е.Н. Анализ распространенности и факторов риска развития остеоартрита в популяции. Современная ревматология. 2019;13(2):105–111. https://doi.org/10.14412/1996-7012-2019-2-105-111. Portyannikova O.O., Tsvinger S.M., Govorin A.V., Romanova E.N. Analysis of the prevalence and risk factors of osteoarthritis in a population. Modern Rheumatology Journal. 2019;13(2):105–111. (In Russ.) https://doi.org/10.14412/1996-7012-2019-2-105-111.

2. Полякова Ю.В., Папичев Е.В., Ахвердян Ю.Р., Сивордова Л.Е., Заводовский Б.В. Новая коронавирусная инфекция – прямое и косвенное влияние на пациентов с болезнями костно-мышечной системы и соединительной ткани. Современные проблемы науки и образования. 2021;(6). Режим доступа: https://science-education.ru/ru/article/view?id=31342. Poljakova Ju.V., Papichev E.V., Ahverdjan Ju.R., Sivordova L.E., Zavodovskij B.V. New coronavirus infection – direct and indirect impact on patients with diseases of the musculoskeletal system and connective tissue. Modern Problems of Science and Education. 2021;(6). (In Russ.) Available at: https://science-education.ru/ru/article/view?id=31342.

3. Вялков А.И., Гусев Е.И., Зборовский А.Б., Насонова В.А. Основные задачи международной декады (The Bone and Joint Decade 2000–2010) в совершенствовании борьбы с наиболее распространенными заболеваниями опорно-двигательного аппарата в России. Научно-практическая ревматология. 2001;(2):4–8. Режим доступа: https://cyberleninka.ru/article/n/osnovnye-zadachi-mezhdunarodnoy-dekady-the-bone-and-joint-decade-2000-2010-v-sovershenstvovanii-borby-s-naibolee-rasprostranennymi. Vjalkov A.I., Gusev E.I., Zborovskij A.B., Nasonova V.A. The main objectives of the international decade (The Bone and Joint Decade 2000-2010) in improving the fight against the most common diseases of the musculoskeletal system in Russia. Rheumatology Science and Practice. 2001;(2):4–8. (In Russ.) Available at: https://cyberleninka.ru/article/n/osnovnye-zadachimezhdunarodnoy-dekady-the-bone-and-joint-decade-2000-2010-vsovershenstvovanii-borby-s-naibolee-rasprostranennymi.

4. Kolasinski S.L., Neogi T., Hochberg M.C., Oatis C., Guyatt G., Block J. et al. 2019 American College of Rheumatology. Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020;72(2):149–162. https://doi.org/10.1002/acr.24131.

5. Fernandes L., Hagen K.B., Bijlsma J.W.J., Andreassen O., Christensen P., Conaghan P.G. et al. EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Ann Rheum Dis. 2013;72(7):1125–1135. https://doi.org/10.1136/annrheumdis-2012-202745.

6. Geenen R., Overman C.L., Christensen R., Åsenlöf P., Capela S., Huisinga K.L. et al. EULAR recommendations for the health professional’s approach to pain management in inflammatory arthritis and osteoarthritis. Ann Rheum Dis. 2018;77(6):797–807. https://doi.org/10.1136/annrheumdis-2017-212662.

7. Kloppenburg M., Kroon F.P., Blanco F.J., Doherty M., Dziedzic K.S., Greibrokk E. et al. 2018 update of the EULAR recommendations for the management of hand osteoarthritis. Ann Rheum Dis. 2019;78(1):16–24. https://doi.org/10.1136/annrheumdis-2018-213826.

8. Gwinnutt J.M., Wieczorek M., Balanescu A., Bischoff-Ferrari H.A., Boonen A., Cavalli G. et al. 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2022. https://doi.org/10.1136/annrheumdis-2021-222020.

9. Bruyère O., Honvo G., Veronese N., Arden N.K., Branco J., Curtis E.M. 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):337–350. https://doi.org/10.1016/j.semarthrit.2019.04.008.

10. Brophy R.H., Fillingham Y.A. AAOS Clinical Practice Guideline Summary: Management of Osteoarthritis of the Knee (Nonarthroplasty), Third Edition. J Am Acad Orthop Surg. 2022;30(9):e721-e729. https://doi.org/10.5435/JAAOS-D-21-01233.

11. Тихилов Р.М., Корнилов Н.Н., Куляба Т.А., Петухов А.И., Сараев А.В., Божкова С.В. и др. Гонартроз: клинические рекомендации. 2021. Режим доступа: https://cr.minzdrav.gov.ru/schema/667_1. Tikhilov R.M., Kornilov N.N., Kulyaba T.A., Petukhov A.I., Saraev A.V., Bozhkova S.V. et al. Gonarthrosis: clinical guidelines. 2021. (In Russ.) Available at: https://cr.minzdrav.gov.ru/schema/667_1.

12. Лила А.М., Алексеева Л.И., Таскина Е.А. Современные подходы к терапии остеоартрита с учетом обновленных международных рекомендаций. РМЖ. Медицинское обозрение. 2019;(11):48–52. Режим доступа: https://www.rmj.ru/articles/revmatologiya/Sovremennye_podhody_k_terapii_osteoartrita_s_uchetom_obnovlennyh_meghdunarodnyh_rekomendaciy. Lila A.M. Alekseeva L.I. Taskina E.A. Modern approaches to the treatment of osteoarthritis, taking into account updated international recommendations. RMJ. Medical Review. 2019;(11):48–52. (In Russ.) Available at: https://www.rmj.ru/articles/revmatologiya/Sovremennye_podhody_k_terapii_osteoartrita_s_uchetom_obnovlennyh_meghdunarodnyh_rekomendaciy.

13. Carlson V.R., Ong A.C., Orozco F.R., Hernandez V.H., Lutz R.W., Post Z.D. Compliance With the AAOS Guidelines for Treatment of Osteoarthritis of the Knee: A Survey of the American Association of Hip and Knee Surgeons. J Am Acad Orthop Surg. 2018;26(3):103–107. https://doi.org/10.5435/JAAOS-D-17-00164.

14. Uson J., Rodriguez-García S.C., Castellanos-Moreira R., O’Neill T.W., Doherty M., Boesen M. et al. EULAR recommendations for intra-articular therapies. Ann Rheum Dis. 2021;80(10):1299–1305. https://doi.org/10.1136/annrheumdis-2021-220266.

15. Bruyère O., Cooper C., Pelletier J.P., Branco J., Brandi L.M., Guillemin F. 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):253–263. https://doi.org/10.1016/j.semarthrit.2014.05.014.

16. Delbarre A., Amor B., Bardoulat I., Tetafort A., Pelletier-Fleury N., Orgel J.P.R.O. Do intra-articular hyaluronic acid injections delay total knee replacement in patients with osteoarthritis – A Cox model analysis. PLoS ONE. 2017;12(11):e0187227. https://doi.org/10.1371/journal.pone.0187227.

17. Abbott T., Altman R.D., Dimef R., Fredericson M., Vad V., Vitanzo P.Jr. et al. Do hyaluronic acid injections delay total knee replacement surgery? Arthritis Rheum. 2013;65:910–911. https://doi.org/10.1371/journal.pone.0187227.

18. Shen D., Chen M., Chen K., Wang T., Lu L., Yang X. Efficacy of hyaluronic acid after knee arthroscopy: A systematic review and meta-analysis. J Rehabil Med. 2018;50(10):860–865. https://doi.org/10.2340/16501977-2366.

19. Pham T., van der Heijde D., Altman R.D., Anderson J.J., Bellamy N., Hochberg M. et al. OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage. 2004;12(5):389–399. https://doi. org/10.1016/j.joca.2004.02.001.

20. Brander V., Skrepnik N., Petrella R.J., Jiang G.L., Accomando B., Vardanyan A. Evaluating the use of intra-articular injections as a treatment for painful hip osteoarthritis: a randomized, double-blind, multicenter, parallel-group study comparing a single 6-mL injection of hylan G-F 20 with saline. Osteoarthritis Cartilage. 2019;27(1):59–70. https://doi.org/10.1016/j.joca.2018.08.018.

21. Заводовский Б.В., Сивордова Л.Е., Полякова Ю.В., Ахвердян Ю.Р., Папичев Е.В. Оценка безопасности, переносимости и эффективности первого отечественного генерика ацеклофенака у пациентов с недифференцированным артритом. Терапевтический архив. 2020;92(5):61–68. https://doi.org/10.26442/00403660.2020.05.000589. Zavodovsky B.V., Sivordova L.E., Polyakova Yu.V., Akhverdyan Yu.R., Papichev E.V. Assessment of the safety, tolerability and effectiveness of the first domestic generic aceclofenac in patients with undifferentiated arthritis. Terapevticheskii Arkhiv. 2020;92(5):61–68. (In Russ.) https://doi.org/10.26442/00403660.2020.05.000589.

22. Заводовский Б.В., Папичев Е.В., Сивордова Л.Е., Полякова Ю.В., Ахвердян Ю.Р. Сравнительная эффективность и безопасность длительного и кратковременного приема нестероидных противовоспалительных препаратов для лечения остеоартрита коленного сустава. Травматология и ортопедия России. 2020;6(2):120–127. https://doi.org/10.21823/2311-2905-2020-26-2-120-127. Zavodovskiy B.V., Papichev E.V., Sivordova L.E., Polyakova Yu.V., Akhverdyan Yu.R. The comparative efficacy and safety of longand shortterm continuous use of nonsteroidal anti-inflammatory drugs for the treatment of knee osteoarthritis. Traumatology and Orthopedics of Russia. 2020;6(2):120–127. (In Russ.) https://doi.org/10.21823/2311-2905-2020-26-2-120-127.

23. Nicholls M., Shaw P., Niazi F., Bhandari M., Bedi A. The Impact of Excluding Patients with End-Stage Knee Disease in Intra-Articular Hyaluronic Acid Trials: A Systematic Review and Meta-Analysis. Adv Ther. 2019;36(1):147–161. https://doi.org/10.1007/s12325-018-0847-1.

24. Lapane K.L., Liu S.H., Dubé C.E., Driban J.B., McAlindon T.E., Eaton C.B. Factors Associated with the Use of Hyaluronic Acid and Corticosteroid Injections among Patients with Radiographically Confirmed Knee Osteoarthritis: A Retrospective Data Analysis. Clin Ther. 2017;39(2):347–358. https://doi.org/10.1016/j.clinthera.2017.01.006.

25. Chevalier X., Jerosch J., Goupille P., van Dijk N., Luyten F.P., Scott D.L. et al. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis. 2010;69(1):113–119. https://doi.org/10.1136/ard.2008.094623.

26. Лила А.М., Алексеева Л.И., Таскина Е.А. Современные подходы к терапии остеоартрита с учетом обновленных международных рекомендаций. РМЖ. Медицинское обозрение. 2019;(2):48–52. Режим доступа: https://www.rmj.ru/archive/revmatologiya-11-2-2019. Lila A.M., Alekseeva L.I., Taskina E.A. Modern approaches to osteoarthritis therapy based on updated international recommendations. RMJ. Medical Review. 2019;(2):48–52. (In Russ.) Available at: https://www.rmj.ru/archive/revmatologiya-11-2-2019.

27. Gregori D., Giacovelli G., Minto C., Barbetta B., Gualtieri F., Azzolina D. et al. Association of pharmacological treatments with long-term pain control in patients with knee osteoarthritis: a systematic review and meta-analysis. JAMA. 2018;320(24):2564–2579. https://doi.org/10.1001/jama.2018.1931.

28. Conrozier T., Raman R., Chevalier X., Henrotin Y., Monfort J., Diraçoglù D. et al. Viscosupplementation for the treatment of osteoarthritis. The contribution of EUROVISCO group. Ther Adv Musculoskelet Dis. 2021;13:1759720X211018605. https://doi.org/10.1177/1759720X211018605.

29. Steinmeyer J., Bock F., Stöve J., Jerosch J., Flechtenmacher J. Pharmacological treatment of knee osteoarthritis: special considerations of the new German guideline. Orthop Rev. (Pavia). 2018;10(4):7782. https://doi.org/10.4081/or.2018.7782.

30. Conrozier T., Eymard F., Afif N., Balblanc J.C., Legré-Boyer V., Chevalier X.; Happyvisc Study Group. Safety and efficacy of intra-articular injections of a combination of hyaluronic acid and mannitol (HAnOX-M) in patients with symptomatic knee osteoarthritis: Results of a double-blind, controlled, multicenter, randomized trial. Knee. 2016;23(5):842–848. https://doi.org/10.1016/j.knee.2016.05.015.