Posttraumatic Osteoarthritis. Effective Combination of Non-steroidal Anti-inflammatory Drugs and SYSADOA
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Abstract
Osteoarthritis (OA) is the most frequent joint desease and is the leading cause of the functional loss and disability among older patients. The heterogeneity of OA determines the absence of a 100% effective therapeutic strategy for all patients. In addition, this heterogeneity may be the main reason for the failure of clinical trials of therapeutic agents designed to restore cartilage.
The SYSADOA group of drugs, in particular – glucasamine and chondroitin, is among the most studied compounds, have a good safety profile and showed proven efficacy in the early stages of osteoarthritis. The use of these drugs in combination with non-steroidal anti-inflammatory drugs (NSAIDs) is widespread in the world and is included in the recommendations of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis – ESCEO.
The objective: to assess the clinical efficacy and safety of the combination of diclofenac potassium 50 mg, chondroitini sulfatis 400 mg and glucosamini sulfatis 500 mg; chondroitini sulfatis 400 mg and glucosamini sulfatis 500 mg in treatment of patients with knee and ankle post-traumatic osteoarthritis in the early stages (I–II according to Kelgren and Lawrence).
Materials and methods. The study was designed as a randomized comparative prospective placebo-controlled in parallel groups. The level of evidence for this study is II-B. Patients of the main group N1 underwent surgical treatment for joint trauma and had a radiographically and clinically confirmed diagnosis: post-traumatic osteoarthritis stage I-II (according to Kelgren and Lawrence) of the ankle (N1.1=15) and knee (N1.2=15) joints. Time from injury and surgery was 14.3±2.3 months.
Patients from main group received combination of diclofenac potassium, chondroitini sulfatis and glucosamini sulfatis for 10 days at the begining of the treatment course, and followed with combination of chondroitin and glucosamin for 3 months further. The comparison group included similar patients in terms of the number, gender, age and the nature of OA (N2.1=15; N2.2=15), these patients were prescribed diclofenac potassium 50 mg 2 times a day (for the first 10 days of treatment), and further followed with placebo (for the next 3 months).
All enrolled patients also were prescribed basic non-pharmacological treatment, which included body weight control, physical therapy, mechanotherapy, exercises, together with orthopedic devices to unload and stabilize the affected joint.
The results of treatment were assessed clinically at 3 months and 6 months after the start of treatment using VAS, functional state of the ankle (according to AOFAS) and knee (according to Lysholm scale); on each visit information about adverse reactions was collected.
Results. After 3 months, the intensity of pain according to VAS in the N1.1 group was 24.8±2.1 points, and in the N2.1 group 29.2±3.2 (p<0.05). After 6 months, the VAS results were accordingly 15.1±3.4 vs 26.7±0.9 (p<0.01). The functional capacity of the ankle joint, evaluated by AOFAS, after 3 months in N1.1 group achieved 81.7±4.3 and 68.4±5.6 points in N2.1 group (p<0.01). At 6 months, the AOFAS score was 93.9±3.8 vs 79.4±4.1 (p<0.05). After 3 months VAS score in patients with early stages of knee OA (group N1.2 and N2.2) was 21.2±1.9 vs 28.3±3.1 mm (p<0.05); after 6 months – 14.7±1.4 vs 23.9±2.8 mm (p<0.01). The level of functional activity after 3 months of treatment according to the Lysholm scale achieved 86.8±2.9 points versus 68.4±5.6 points (p<0.05) and after 6 months - continued to grow and got to 97.4±1.2 vs 86.2±2.9 points (p<0.01). There were no statistical differences in number and intensity of the adverse events in the studied groups (p>0.5).
Conclusions. In the early stages of post-traumatic osteoarthritis of the knee and ankle joints (I–II according to Kelgren and Lawrence), a 3-month course of treatment with combination of NSAID and SYSADOA (diclofenac with chondroitin and glucosamin), followed by further treatment with SYSADOA (chondroitin and glucosamine) demonstrated superior efficacy compared to the placebo/standard treatment with the same level of safety.
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References
Arden NK, Perry TA, Bannuru RR, Bruyere O, Cooper C, Haugen IK, et al. Nonsurgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol. 2020;17:59. doi: 10.1038/s41584-020-00523-9.
Bally M, Dendukuri N, Rich B, Nadeau L, Helin-Salmivaara A, Garbe E, et al. Risk of acute myocardial infarction with NSAIDs in real world use: bayesian metaanalysis of individual patient data. BMJ. 2017;357:j1909. doi: 10.1136/bmj.j1909.
Bruyerea O, Honvo G, Veronese N, Arden NK, Branco J, Curtis EM, 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. doi: 10.1016/j.semarthrit.2019.04.008.
Carlson AK, Rawle RA, Wallace CW, Brooks EG, Adams E, Greenwood MC, et al. Characterization of synovial fluid metabolomic phenotypes of cartilage morphological changes associated with osteoarthritis. Osteoarthritis Cartilage. 2019;27(8):1174-84. doi:10.1016/j.joca.2019.04.007.
Chen D, Shen J, Zhao W, Wang T, Han L, Hamilton JL, et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res. 2017;5:16044. doi: 10.1038/boneres.2016.44.
Da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni 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. 2017;390(10090):e21-e33. doi: 10.1016/S0140-6736(17)31744-0.
Deveza LA, Nelson AE, Loeser RF. Phenotypes of osteoarthritis: current state and future implications. Clin Exp Rheumatol. 2019;37 Suppl 120(5):64-72.
Felson DT. Osteoarthritis of the knee. N Engl J Med. 2006;354(8):841-8. doi: 10.1056/NEJMcp051726.
Fransen M, Agaliotis M, Nairn L, Votrubec M, Bridgett L, Steve S, et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomized placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2015;74(5):851-8. doi: 10.1136/annrheumdis-2013-203954.
Fuggle N, Curtis E, Shaw S, Spooner L, Bruyère O, Ntani G, et al. Safety of opioids in osteoarthritis: outcomes of a systematic review and meta-analysis. Drugs Aging. 2019;36(Suppl.1):129-43. doi: 10.1007/s40266-019-00666-9.
Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745-59. doi: 10.1016/S0140-6736(19)30417-9.
Kitaoka HB, Alexander IJ, Adelaar RS, Nunley JA, Myerson MS, Sanders M. Clinical rating systems for the ankle-hindfoot,midfoot, hallux, and lesser toes. Foot Ankle Int. 1994;15:349-53. doi: 10.1177/107110079401500701.
Latourte A, Kloppenburg M, Richette P. Emerging pharmaceutical therapies for osteoarthritis. Nat Rev Rheumatol. 2020;16(12):673-88. doi: 10.1038/s41584-020-00518-6.
Leeb ВA, Montag K, Smolen JS. Metaanalisis of chondroitinsulfate in the treatment of Osteoarthritis. J Rheumatol. 2000;27(1):205-11.
Leopoldino AO, Machado GC, Ferreira PH, Pinheiro MB, Day R, McLachlan AJ, et al. Paracetamol versus placebo for knee and hip osteoarthritis. Cochrane Database Syst. Rev. 2019;2:D13273. doi: 10.1002/14651858.CD013273.
Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64(6):1697-707. doi:10.1002/art.34453.
Mazieres В, Combe B, Van AP, Tondut J, Grynfeltt M. Chondroitin sulfate in osteoarthritis knee: a prospective, double-blind, placebo-controlled multicenter clinical stady. J Rheumatol. 2001;28(1):173-81.
McAlindon Т, LaValley M, Gulin JP, Felson DT. Glucosamin and Chondroitin for treatment of osteoarthritis: a systematic quality assessment and metaanalysis. JAMA. 2000;283(11):1469-75. doi: 10.1001/jama.283.11.1469.
Nelson AE, Fang F, Arbeeva L, Cleveland RJ, Schwartz TA, Callahan LF, et al. A machine learning approach to knee osteoarthritis phenotyping: data from the FNIH Biomarkers Consortium. Osteoarthritis Cartilage. 2019;27(7):994-1001. doi: 10.1016/j.joca.2018.12.027.
Oo WM, Yu SP-C, Daniel MS, Hunter DJ. Disease-modifying drugs in osteoarthritis: current understanding and future therapeutics. Expert Opin Emerging Drugs. 2018;23(4):331-47. doi: 10.1080/14728214.2018.1547706.
Persiani S, Rotini R, Trisolino G, Rovati LC, Locatelli M, Paganini D, et al. Synovial and plasma glucosamine concentrations in osteoarthritic patients following oral crystalline glucosamine sulphate at therapeutic dose. Osteoarthr Cartil. 2007;15(7):764-72. doi: 10.1016/j.joca.2007.01.019.
Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, et al. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357(9252):251-6. doi: 10.1016/S0140-6736(00)03610-2.
Roman-Blas JA, Mendoza-Torres LA, Largo R, Herrero-Beaumont G. Setting up distinctive outcome measures for each osteoarthritis phenotype. Ther Adv Musculoskelet. 2020;12:1759720X20937966. doi: 10.1177/1759720X20937966.
Bіlovol OM, Kniazkova ІІ, Tveretіnov OB. Suchasny aspekty vykorystannia nesteroidnykh protyzapalnykh preparativ: metod.rekomend. Kyiv; 2008. 34 p.
Bur’ianov OA, Omelchenko TM, Mіkhnevich OE, redaktor. Osteoartroz: henezys, diahnostyka, likuvannia. Кyiv: Lenvit; 2009. 203 p.
Zupanets ІA, Shebeko SK. Farmakolohichne doslidzhennia analhetychnoi aktyvnosti Terafleksu ta Terafleksu Advans. Zdorovia Ukr. 2008;21/1:70-1.
Babak OI, Bіlovola OM, Chekman ІS. Klinichna farmakolohiia. Kyiv: Medytsyna; 2008. 768 p.