Comparison of the Effect of Intra-Articular Injection of Autologous (Orthokine) Interleukin-1 Receptor Antagonist (IL-1Ra) and Hyaluronic Acid in Pain Control of Knee Osteoarthritis
Background: Due to the limitations of more common treatments of osteoarthritis, pharmaceutical research has been increasingly conducted during the past two decades with the aim of determining the rate of recovery of the disease' symptoms and making the process of disease progression slow. The purpose of this study was to compare the effect of intra-articular injection of autologous interleukin-1 Receptor Antagonist and hyaluronic acid in pain control of knee osteoarthritis.
Materials and Methods: A total of 60 patients with knee osteoarthritis were allocated to two groups of 30 in this randomized double-blind clinical trial. In the intervention group, injection of 2 milliliter of interleukin-1 receptor antagonist (Orthokine) into the knee joint was performed three times at intervals of one week (base time, seventh day and fourteenth day). In the control group, three injections of two milliliters of hyaluronic acid solution into the knee joint were performed at intervals of one week. Pain, symptoms, daily activities, sport-recreational performance, and knee-related quality of life were five outcomes investigated by completing two questionnaires, the knee injury and osteoarthritis outcome score (KOOS), Western Ontario, and McMaster Universities Arthritis Index (WOMAC) by the patients on two occasions before the start of treatment and six months after the last injection. Repeated measure and t-test were statistical tests used in this study.
Results: The mean score of pain in the first month (p=0.005) and the sixth (p=0.049) in the intervention group was less than the control group. Based on the scores of the KOOS questionnaire, the mean score of symptoms (p=0.006), daily activities (p=0.001) and sport-recreational performance (p=0.037) in the Orthokine group were higher than the hyaluronic acid group after six months. Also, the results of the questionnaire WOMAC show that while before the start of treatment, the mean of physical performance in the Orthokine group is greater than the control group, there is no difference in any of the indicators of pain, dryness of the joint, physical performance, and total score (p=0.319) in the sixth month.
Conclusion: According to the findings of this study, it seems that Orthokine has beneficial biological effects in patients with knee osteoarthritis. Intra-articular injection of Orthokine is a low invasive, safe and effective method, which can be considered as an appropriate choice in patients with chronic knee pain.
Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bulletin of the World Health Organization. 2003;81:646-56.
Buckwalter JA, Martin JA. Sports and osteoarthritis. Current opinion in rheumatology. 2004;16(5):634-9.
Kim HJ, Lee YH, Kim CK. Biomarkers of muscle and cartilage damage and inflammation during a 200 km run. European journal of applied physiology. 2007;99(4):443-7.
Lequesne MG, Dang N, Lane NE. Sport practice and osteoarthritis of the limbs. Osteoarthritis and cartilage. 1997;5(2):75-86.
Martel-Pelletier J, Boileau C, Pelletier JP, Roughley PJ. Cartilage in normal and osteoarthritis conditions. Best practice & research Clinical rheumatology. 2008;22(2):351-84.
Lane NE, Brandt K, Hawker G, Peeva E, Schreyer E, Tsuji W, et al. OARSI-FDA initiative: defining the disease state of osteoarthritis. Osteoarthritis and cartilage. 2011;19(5):478-82.
Neustadt DH. Intra-articular injections for osteoarthritis of the knee. Cleveland Clinic journal of medicine. 2006;73(10):897-8, 901-4, 6-11.
Reeuwijk KG, de Rooij M, van Dijk GM, Veenhof C, Steultjens MP, Dekker J. Osteoarthritis of the hip or knee: which coexisting disorders are disabling? Clinical rheumatology. 2010;29(7):739-47.
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-analysisPharmacological Treatments for Pain Control in Knee OsteoarthritisPharmacological Treatments for Pain Control in Knee Osteoarthritis. JAMA. 2018;320(24):2564-79.
Review: evidence exists for 33 different treatment options for osteoarthritis of the knee. Evidence Based Medicine. 2004;9(3):81-.
Cannon GW, Caldwell JR, Holt P, McLean B, Seidenberg B, Bolognese J, et al. Rofecoxib, a specific inhibitor of cyclooxygenase 2, with clinical efficacy comparable with that of diclofenac sodium: results of a one-year, randomized, clinical trial in patients with osteoarthritis of the knee and hip. Rofecoxib Phase III Protocol 035 Study Group. Arthritis and rheumatism. 2000;43(5):978-87.
da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Juni P, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet (London, England). 2017;390(10090):e21-e33.
Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, et al. Cardiovascular Events Associated with Rofecoxib in a Colorectal Adenoma Chemoprevention Trial. New England Journal of Medicine. 2005;352(11):1092-102.
McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselectiveinhibitors of cyclooxygenase 2. Jama. 2006;296(13):1633-44.
Abramson SB, Amin A. Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology (Oxford, England). 2002;41(9):972-80.
Meijer H, Reinecke J, Becker C, Tholen G, Wehling P. The production of anti-inflammatory cytokines in whole blood by physico-chemical induction. Inflammation research : official journal of the European Histamine Research Society [et al]. 2003;52(10):404-7.
Baselga Garcia-Escudero J, Miguel Hernandez Trillos P. Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study. PloS one. 2015;10(12):e0145551.
Wehling P, Moser C, Frisbie D, McIlwraith CW, Kawcak CE, Krauspe R, et al. Autologous conditioned serum in the treatment of orthopedic diseases: the orthokine therapy. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy. 2007;21(5):323-32.
Watterson JR, JM. E. Viscosupplementation: therapeutic mechanisms and clinical potential in osteoarthritis of the knee. J Am Acad Orthop Surg 2000;8:277-84.
Auw Yang KG, Raijmakers NJ, van Arkel ER, Caron JJ, Rijk PC, Willems WJ, et al. Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial. Osteoarthritis and cartilage. 2008;16(4):498-505.
Altman RD, Akermark C, Beaulieu AD, Schnitzer T. Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee. Osteoarthritis and cartilage. 2004;12(8):642-9.
Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology (Oxford, England). 2002;41(3):279-84.
Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Archives of internal medicine. 2002;162(18):2113-23.
Baltzer AW, Moser C, Jansen SA, Krauspe R. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis and cartilage. 2009;17(2):152-60.
Astolfi M, McGuire K, Kaminski TW. The effectiveness of autologous conditioned serum in the treatment of knee osteoarthritis. Journal of sport rehabilitation. 2014;23(4):365-9.
Rutgers M, Saris DB, Dhert WJ, Creemers LB. Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection. Arthritis research & therapy. 2010;12(3):R114.
Frisbee DD, Ghivizzani SC, Robbins PD, al. e. Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene, Gene Ther. 2002;9 12-20.
Fernandes J, Tardiff G, Martel-Pelletier J, al. e. In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritis rabbit knee joints,. Am J Pathol. 1999;154 1159-69.
Zhang X, Mao Z, C. Y. Suppression of early experimental osteoarthritis by gene transfer of interleukin-1 receptor antagonist and interleukin-10. J Orthop Re. 2004;22 742-50.
Chevalier X, Giraudeau B, Conrozier T, al. e. Safety study of intra-articular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study. J Rheumatol. 2005;32 1317-23.
Paradowski PT, Bergman S, Sundén-Lundius A, Lohmander LS, EM. R. Knee complaints vary with age and gender in the adult population. Population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS). BMC Musculoskelet Disord. 2006;2(38).
Waddell DD, DWC. B. Total knee replacement delayed with Hylan G-F 20 use in patients with grade IV osteoarthritis. J Manag Care Pharm. 2007;13:113-21.
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.
Razmjou H, Yee A, Ford M, Finkelstein JA. Response shift in outcome assessment in patients undergoing total knee arthroplasty. The Journal of bone and joint surgery American volume. 2006;88(12):2590-5.
Frizziero A, Giannotti E, Oliva F, Masiero S, N. M. Autologous conditioned serum for the treatment of osteoarthritis and other possible applications in musculoskeletal disorders. Br Med Bull. 2013;105:169-84.
Zarringam D, Bekkers JEJ, DBF. S. Long-term Effect of Injection Treatment for Osteoarthritis in the Knee by Orthokin Autologous Conditioned Serum. Cartilage. 2018 9(2):140-5.