Эффективность и безопасность применения неденатурированного коллагена II типа у пациентов с остеоартритом коленных суставов: многоцентровое проспективное двойное слепое плацебо-контролируемое рандомизированное исследование
Эффективность и безопасность применения неденатурированного коллагена II типа у пациентов с остеоартритом коленных суставов: многоцентровое проспективное двойное слепое плацебо-контролируемое рандомизированное исследование
Alekseeva LI, Kashevarova NG, Taskina EA, Strebkova EA, Korotkova TA, Sharapova EP, Savushkina NM, Lila AM, Shostak NA, Mazurov VI, Nesterovich II, Dedkova VA, Vasilyuk VB, Egorova NV, Leontyeva MA, Yakupova SP, Vinogradova IB, Sorotskaya VN, Shirokova LYu. Efficacy and safety of undenatured type II collagen in patients with knee osteoarthritis: a multicenter, prospective, double-blind, placebo-controlled, randomized trial. Terapevticheskii Arkhiv (Ter. Arkh.). 2024;96(5):500–510. DOI: 10.26442/00403660.2024.05.202788
Эффективность и безопасность применения неденатурированного коллагена II типа у пациентов с остеоартритом коленных суставов: многоцентровое проспективное двойное слепое плацебо-контролируемое рандомизированное исследование
Обоснование. Немедикаментозные методы лечения, основанные на приеме коллагена в качестве биологически активной добавки, позиционируют как новый объект интереса для поддержки профилактического или терапевтического эффекта у пациентов с остеоартритом (ОА). Цель. В многоцентровом проспективном двойном слепом плацебо-контролируемом рандомизированном исследовании оценить эффективность и безопасность применения комплекса Артнео, содержащего неденатурированный куриный коллаген II типа, у пациентов с ОА коленных суставов (КС). Материалы и методы. В исследование включены 212 амбулаторных пациентов из 12 центров Российской Федерации с диагнозом ОА КС II и III стадии по Келлгрену–Лоуренсу: 171 (80,7%) женщина, 41 (19,3%) мужчина, средний возраст которых составил 60,2±9,0 года (40–75 лет). Исследуемую популяцию случайным образом с использованием интерактивной системы веб-ответа (IWRS) распределили в равном соотношении на 2 группы: группа «Aртнео» (основная группа) – 106 пациентов, принимавших препарат по 1 капсуле 1 раз в день на протяжении 180 дней; группа «Плацебо» (группа сравнения) – 106 больных, у которых форма выпуска и режим приема были идентичны. На фоне терапии проводили оценку индекса WOMAC, KOOS, боли по Визуальной аналоговой шкале, качества жизни по опроснику EQ-5D, потребности в нестероидных противовоспалительных препаратах. Всем пациентам выполнили клинический, общий и биохимический анализы крови, ультразвуковое исследование целевого КС. Результаты. Комбинация Артнео, содержащая неденатурированный куриный коллаген II типа, позитивно влияет на все клинические проявления ОА: эффективно уменьшает боль, скованность, улучшает функциональное состояние суставов и качество жизни. Кроме того, она обладает хорошим профилем безопасности и превосходит плацебо по всем исследуемым параметрам. Заключение. Результаты проведенного исследования подтверждают хорошую эффективность и безопасность комбинации Артнео у пациентов с ОА КС.
Ключевые слова: остеоартрит, неденатурированный коллаген II типа, Артнео, плацебо, эффективность, безопасность
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Background. Non-pharmacological treatments based on collagen as a dietary supplement are emerging as a new area of interest to support preventive or therapeutic effects in patients with osteoarthritis (OA). Aim. In a multicenter, prospective, double-blind, placebo-controlled, randomized study, to evaluate the effectiveness and safety of the use of the Artneo complex containing undenatured chicken collagen type II in patients with OA of the knee joints. Materials and methods. The study enrolled 212 outpatients from 12 centers in the Russian Federation with knee OA, stages II and III according to the Kellgren–Lawrence classification. The participants included 171 women (80.7%) and 41 men (19.3%), with an average age of 60.2±9.0 years (range: 40 to 75 years). The study population was randomly allocated in equal proportions into two groups using an interactive web response system (IWRS). Group 1 (Artneo) consisted of 106 patients who took one capsule of the drug once daily for 180 days. Group 2 (Placebo) also had 106 patients, with the dosage form and regimen identical to Group 1. During the treatment period, the following outcomes were assessed: WOMAC index, KOOS, pain according to VAS, quality of life using the EQ-5D questionnaire, and the need for NSAIDs. All patients underwent a clinical blood test, general urine analysis, biochemical blood test, and ultrasound examination of the affected knee joint. Results. In a prospective, double-blind, placebo-controlled, randomized study, it was demonstrated that the Artneo combination, containing undenatured chicken collagen type II, has a positive effect on all clinical manifestations of OA: it effectively reduces pain, stiffness, and improves the functional state of joints and quality of life. It has a good safety profile and is superior to placebo in all parameters studied. Conclusion. The results of the study confirm the good effectiveness and safety of the Artneo combination in patients with OA of the knee joints.
Keywords: osteoarthritis, undenatured type II collagen, Artneo, placebo, effectiveness, safety
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4. Liew JW, King LK, Mahmoudian A, et al. A scoping review of how early-stage knee osteoarthritis has been defined. Osteoarthritis Cartilage. 2023;31(9):1234-41. DOI:10.1016/j.joca.2023.04.015
5. Yusuf E. Pharmacologic and Non-Pharmacologic Treatment of Osteoarthritis. Curr Treat Options Rheum. 2016;2:111-25. DOI:10.1007/s40674-016-0042-y
6. Curtis E, Fuggle N, Shaw S, et al. Safety of Cyclooxygenase-2 Inhibitors in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. Drugs Aging. 2019;36(Suppl. 1):25-44. DOI:10.1007/s40266-019-00664-x
7. Bruyère O, Honvo G, Veronese N, 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
8. Reginster JY, Veronese N. Highly purified chondroitin sulfate: a literature review on clinical efficacy and pharmacoeconomic aspects in osteoarthritis treatment. Aging Clin Exp Res. 2021;33(1):37-47. DOI:10.1007/s40520-020-01643-8
9. Honvo G, Lengelé L, Charles A, et al. Role of Collagen Derivatives in Osteoarthritis and Cartilage Repair: A Systematic Scoping Review With Evidence Mapping. Rheumatol Ther. 2020;7(4):703-40. DOI:10.1007/s40744-020-00240-5
10. Nimni ME, Harkness RD. Collagen. Volume 1. CRC Press; Boca Raton, FL, USA. 2018.
11. Mahmood A, Patel D, Hickson B, et al. Recent Progress in Biopolymer-Based Hydrogel Materials for Biomedical Applications. Int J Mol Sci. 2022;23(3). DOI:10.3390/ijms23031415
12. Castile JD, Taylor KM, Buckton G. The influence of incubation temperature and surfactant concentration on the interaction between dimyristoylphosphatidylcholine liposomes and poloxamer surfactants. Int J Pharm. 2001;221(1-2):197-209. DOI:10.1016/s0378-5173(01)00685-8
13. Sbricoli L, Guazzo R, Annunziata M, et al. Selection of Collagen Membranes for Bone Regeneration: A Literature Review. Materials (Basel). 2020;13(3). DOI:10.3390/ma13030786
14. Xu Q, Torres JE, Hakim M, et al. Collagen- and hyaluronic acid-based hydrogels and their biomedical applications. Mater Sci Eng R Rep. 2021;146. DOI:10.1016/j.mser.2021.100641
15. El Blidi O, Omari NE, Balahbib A, et al. Extraction Methods, Characterization and Biomedical Applications of Collagen: A Review. Biointerface Res Appl Chem. 2021;11:13587-613. DOI:10.33263/BRIAC115.1358713613
16. Rajabimashhadi Z, Gallo N, Salvatore L, Lionetto F. Collagen Derived from Fish Industry Waste: Progresses and Challenges. Polymers (Basel). 2023;15(3). DOI:10.3390/polym15030544
17. Carr BP, Chen Z, Chung JHY, Wallace GG. Collagen Alignment via Electro-Compaction for Biofabrication Applications: A Review. Polymers (Basel). 2022;14(20). DOI:10.3390/polym14204270
18. Sklenářová R, Akla N, Latorre MJ, et al. Collagen as a Biomaterial for Skin and Corneal Wound Healing. J Funct Biomater. 2022;13(4). DOI:10.3390/jfb13040249
19. Gelse K, Pöschl E, Aigner T. Collagens – structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003;55(12):1531-46. DOI:10.1016/j.addr.2003.08.002
20. Inoue Y, Itoh H, Aoki M, et al. Accelerating effect of soy peptides containing collagen peptides on type I and III collagen levels in rat skin. Biosci Biotechnol Biochem.
2012;76(8):1549-51. DOI:10.1271/bbb.120088
21. Minor AJ, Coulombe KLK. Engineering a collagen matrix for cell-instructive regenerative angiogenesis. J Biomed Mater Res B Appl Biomater. 2020;108(6):2407-16. DOI:10.1002/jbm.b.34573
22. Abedinia A, Mohammadi Nafchi A, Sharifi M, et al. Poultry Gelatin: Characteristics, Developments, Challenges, and Future Outlooks as a Sustainable Alternative for Mammalian Gelatin. Trends Food Sci Technol. 2020;104:14-26. DOI:10.1016/j.tifs.2020.08.001
23. Oliveira VDM, Assis CRD, Costa BDAM, et al. Physical, Biochemical, Densitometric and Spectroscopic Techniques for Characterization Collagen from Alternative Sources: A Review Based on the Sustainable Valorization of Aquatic by-Products. J Mol Struct. 2021;1224:129023. DOI:10.1016/j.molstruc.2020.129023.
24. Fu Y, Therkildsen M, Aluko RE, Lametsch R. Exploration of collagen recovered from animal by-products as a precursor of bioactive peptides: Successes and challenges. Crit Rev Food Sci Nutr. 2019;59(13):2011-27. DOI:10.1080/10408398.2018.1436038
25. Park KS, Park MJ, Cho ML, et al. Type II Collagen Oral Tolerance; Mechanism and Role in Collagen-Induced Arthritis and Rheumatoid Arthritis. Mod Rheumatol. 2009;19:581-9. DOI:10.3109/s10165-009-0210-0
26. Kumar P, Bansal P, Rajnish RK, et al. Efficacy of undenatured collagen in knee osteoarthritis: review of the literature with limited meta-analysis. Am J Transl Res. 2023;15(9):5545-55.
27. Gwinnutt JM, Wieczorek M, Rodríguez-Carrio J, et al. Effects of diet on the outcomes of rheumatic and musculoskeletal diseases (RMDs): systematic review and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs. RMD Open. 2022;8(2). DOI:10.1136/rmdopen-2021-002167
28. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 2011;63 Suppl. 11:S240-52. DOI:10.1002/acr.20543
29. Лила А.М., Алексеева Л.И., Беляева И.Б., и др. Резолюция Совета экспертов «Итоги многоцентрового рандомизированного двойного слепого плацебо-контролируемого исследования Артнео у пациентов с первичным остеоартритом коленного сустава II–III стадии. Современная ревматология. 2023;17(6):136-42 [Lila AM, Alekseeva LI, Belyaeva IB, et al. Resolution of the Council of Experts “Results of a multicenter, randomized, double-blind, placebo-controlled study of ARTNEO in patients with stage II–III primary knee osteoarthritis”. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2023;17(6):136-42 (in Russian)]. DOI:10.14412/1996-7012-2023-6-136-142
30. Lugo JP, Saiyed ZM, Lane NE. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J. 2016;15:14. DOI:10.1186/s12937-016-0130-8
31. Schön C, Knaub K, Alt W, et al. UC-II Undenatured Type II Collagen for Knee Joint Flexibility: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study. J Integr Complement Med. 2022;28(6):540-8. DOI:10.1089/jicm.2021.0365
32. Jain AV, Jain KA, Vijayaraghavan N. AflaB2® and Osteoarthritis: A Multicentric, Observational, Post-Marketing Surveillance Study in Indian Patients Suffering from Knee Osteoarthritis. Int J Res Orthop. 2020;7:110. DOI:10.18203/issn.2455-4510.IntJResOrthop20205570
33. Мазуров В.И., Беляева И.Б., Трофимов Е.А., и др. Сравнение эффективности комбинации неденатурированного коллагена II типа, босвеллиевых кислот, метилсульфонилметана, витаминов С и D3 и комбинации хондроитина сульфата и глюкозамина гидрохлорида в терапии первичного остеоартрита коленного сустава. Терапевтический архив. 2023;95(12):1141-50 [Mazurov VI, Belyaeva IB, Trofimov EA, et al. Comparative efficacy of a combination of undenatured type II collagen, Boswellic acids, methylsulfonylmethane, vitamins C and D3 and a combination of chondroitin sulfate and glucosamine hydrochloride in the treatment of primary osteoarthritis of the knee join. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(12):1141-50 (in Russian)]. DOI:10.26442/00403660.2023.12.202540
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________________________________________________
1. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745-59. DOI:10.1016/S0140-6736(19)30417-9
2. Vos T, Allen C, Arora M. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the global burden of disease study 2015. Lancet. 2016;388(10053):1545-602.
3. Markets and Markets (2020) Osteoarthritis Therapeutics Market – Global Forecast to 2025. Available at: https://www.marketsandmarkets.com/Market-Reports/osteoarthritis-therapeutics-market- 209565994.html?gclid=CjwKCAjw2bmLBhBREiwAZ6ugo5Mqec4ajgZ8UxP4N6eR59eIIuOockof56d8Qu1ivJEQxmLS79_PVxoCKksQAvD_BwE. Accessed: 25.11.2023.
4. Liew JW, King LK, Mahmoudian A, et al. A scoping review of how early-stage knee osteoarthritis has been defined. Osteoarthritis Cartilage. 2023;31(9):1234-41. DOI:10.1016/j.joca.2023.04.015
5. Yusuf E. Pharmacologic and Non-Pharmacologic Treatment of Osteoarthritis. Curr Treat Options Rheum. 2016;2:111-25. DOI:10.1007/s40674-016-0042-y
6. Curtis E, Fuggle N, Shaw S, et al. Safety of Cyclooxygenase-2 Inhibitors in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. Drugs Aging. 2019;36(Suppl. 1):25-44. DOI:10.1007/s40266-019-00664-x
7. Bruyère O, Honvo G, Veronese N, 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
8. Reginster JY, Veronese N. Highly purified chondroitin sulfate: a literature review on clinical efficacy and pharmacoeconomic aspects in osteoarthritis treatment. Aging Clin Exp Res. 2021;33(1):37-47. DOI:10.1007/s40520-020-01643-8
9. Honvo G, Lengelé L, Charles A, et al. Role of Collagen Derivatives in Osteoarthritis and Cartilage Repair: A Systematic Scoping Review With Evidence Mapping. Rheumatol Ther. 2020;7(4):703-40. DOI:10.1007/s40744-020-00240-5
10. Nimni ME, Harkness RD. Collagen. Volume 1. CRC Press; Boca Raton, FL, USA. 2018.
11. Mahmood A, Patel D, Hickson B, et al. Recent Progress in Biopolymer-Based Hydrogel Materials for Biomedical Applications. Int J Mol Sci. 2022;23(3). DOI:10.3390/ijms23031415
12. Castile JD, Taylor KM, Buckton G. The influence of incubation temperature and surfactant concentration on the interaction between dimyristoylphosphatidylcholine liposomes and poloxamer surfactants. Int J Pharm. 2001;221(1-2):197-209. DOI:10.1016/s0378-5173(01)00685-8
13. Sbricoli L, Guazzo R, Annunziata M, et al. Selection of Collagen Membranes for Bone Regeneration: A Literature Review. Materials (Basel). 2020;13(3). DOI:10.3390/ma13030786
14. Xu Q, Torres JE, Hakim M, et al. Collagen- and hyaluronic acid-based hydrogels and their biomedical applications. Mater Sci Eng R Rep. 2021;146. DOI:10.1016/j.mser.2021.100641
15. El Blidi O, Omari NE, Balahbib A, et al. Extraction Methods, Characterization and Biomedical Applications of Collagen: A Review. Biointerface Res Appl Chem. 2021;11:13587-613. DOI:10.33263/BRIAC115.1358713613
16. Rajabimashhadi Z, Gallo N, Salvatore L, Lionetto F. Collagen Derived from Fish Industry Waste: Progresses and Challenges. Polymers (Basel). 2023;15(3). DOI:10.3390/polym15030544
17. Carr BP, Chen Z, Chung JHY, Wallace GG. Collagen Alignment via Electro-Compaction for Biofabrication Applications: A Review. Polymers (Basel). 2022;14(20). DOI:10.3390/polym14204270
18. Sklenářová R, Akla N, Latorre MJ, et al. Collagen as a Biomaterial for Skin and Corneal Wound Healing. J Funct Biomater. 2022;13(4). DOI:10.3390/jfb13040249
19. Gelse K, Pöschl E, Aigner T. Collagens – structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003;55(12):1531-46. DOI:10.1016/j.addr.2003.08.002
20. Inoue Y, Itoh H, Aoki M, et al. Accelerating effect of soy peptides containing collagen peptides on type I and III collagen levels in rat skin. Biosci Biotechnol Biochem.
2012;76(8):1549-51. DOI:10.1271/bbb.120088
21. Minor AJ, Coulombe KLK. Engineering a collagen matrix for cell-instructive regenerative angiogenesis. J Biomed Mater Res B Appl Biomater. 2020;108(6):2407-16. DOI:10.1002/jbm.b.34573
22. Abedinia A, Mohammadi Nafchi A, Sharifi M, et al. Poultry Gelatin: Characteristics, Developments, Challenges, and Future Outlooks as a Sustainable Alternative for Mammalian Gelatin. Trends Food Sci Technol. 2020;104:14-26. DOI:10.1016/j.tifs.2020.08.001
23. Oliveira VDM, Assis CRD, Costa BDAM, et al. Physical, Biochemical, Densitometric and Spectroscopic Techniques for Characterization Collagen from Alternative Sources: A Review Based on the Sustainable Valorization of Aquatic by-Products. J Mol Struct. 2021;1224:129023. DOI:10.1016/j.molstruc.2020.129023.
24. Fu Y, Therkildsen M, Aluko RE, Lametsch R. Exploration of collagen recovered from animal by-products as a precursor of bioactive peptides: Successes and challenges. Crit Rev Food Sci Nutr. 2019;59(13):2011-27. DOI:10.1080/10408398.2018.1436038
25. Park KS, Park MJ, Cho ML, et al. Type II Collagen Oral Tolerance; Mechanism and Role in Collagen-Induced Arthritis and Rheumatoid Arthritis. Mod Rheumatol. 2009;19:581-9. DOI:10.3109/s10165-009-0210-0
26. Kumar P, Bansal P, Rajnish RK, et al. Efficacy of undenatured collagen in knee osteoarthritis: review of the literature with limited meta-analysis. Am J Transl Res. 2023;15(9):5545-55.
27. Gwinnutt JM, Wieczorek M, Rodríguez-Carrio J, et al. Effects of diet on the outcomes of rheumatic and musculoskeletal diseases (RMDs): systematic review and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs. RMD Open. 2022;8(2). DOI:10.1136/rmdopen-2021-002167
28. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 2011;63 Suppl. 11:S240-52. DOI:10.1002/acr.20543
29. Lila AM, Alekseeva LI, Belyaeva IB, et al. Resolution of the Council of Experts “Results of a multicenter, randomized, double-blind, placebo-controlled study of ARTNEO in patients with stage II–III primary knee osteoarthritis”. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2023;17(6):136-42 (in Russian). DOI:10.14412/1996-7012-2023-6-136-142
30. Lugo JP, Saiyed ZM, Lane NE. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J. 2016;15:14. DOI:10.1186/s12937-016-0130-8
31. Schön C, Knaub K, Alt W, et al. UC-II Undenatured Type II Collagen for Knee Joint Flexibility: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study. J Integr Complement Med. 2022;28(6):540-8. DOI:10.1089/jicm.2021.0365
32. Jain AV, Jain KA, Vijayaraghavan N. AflaB2® and Osteoarthritis: A Multicentric, Observational, Post-Marketing Surveillance Study in Indian Patients Suffering from Knee Osteoarthritis. Int J Res Orthop. 2020;7:110. DOI:10.18203/issn.2455-4510.IntJResOrthop20205570
33. Mazurov VI, Belyaeva IB, Trofimov EA, et al. Comparative efficacy of a combination of undenatured type II collagen, Boswellic acids, methylsulfonylmethane, vitamins C and D3 and a combination of chondroitin sulfate and glucosamine hydrochloride in the treatment of primary osteoarthritis of the knee join. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(12):1141-50 (in Russian). DOI:10.26442/00403660.2023.12.202540
34. Mazurov VI, Alekseeva LI, Belyaeva IB, et al. Efficacy, safety and prospects of using a combination of native type II collagen, methylsulfonylmethane, boswellic acids, vitamin C and vitamin D3 in knee osteoarthritis: a resolution of the Expert panel. Terapevticheskii Arkhiv (Ter. Arkh.). 2024;96(1):68-74 (in Russian). DOI:10.26442/00403660.2024.1.202590
1ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия; 2ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия; 3ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России, Санкт-Петербург, Россия; 4СПб ГБУЗ «Клиническая ревматологическая больница №25», Санкт-Петербург, Россия; 5ООО «МСЧ №157», Санкт-Петербург, Россия; 6ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, Санкт-Петербург, Россия; 7ООО «Мейли», Санкт-Петербург, Россия; 8ООО «НИЦ “Эко-безопасность”», Санкт-Петербург, Россия; 9ООО «Энергия Здоровья», Санкт-Петербург, Россия; 10ООО «Клиника Звездная», Санкт-Петербург, Россия; 11ФГБОУ ВО «Казанский государственный медицинский университет» Минздрава России, Казань, Россия; 12ГУЗ «Ульяновская областная клиническая больница», Ульяновск, Россия; 13ФГБОУ ВО «Тульский государственный университет», Тула, Россия; 14ФГБОУ ВО «Ярославский государственный медицинский университет» Минздрава России, Ярославль, Россия; 15ЧОУ ДПО «Институт профессиональной подготовки кадров», Ярославль, Россия
*nat-kash@yandex.ru
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Liudmila I. Alekseeva1, Natalia G. Kashevarova*1, Elena A. Taskina1, Ekaterina A. Strebkova1, Tatiana A. Korotkova1, Evgeniia P. Sharapova1, Natalya M. Savushkina1, Aleksander M. Lila1, Nadezhda A. Shostak2, Vadim I. Mazurov3–5, Irina I. Nesterovich6,7, Viktoriia A. Dedkova8, Vasiliy B. Vasilyuk8, Natalia V. Egorova9, Marina A. Leontyeva10, Svetlana P. Yakupova11, Irina B. Vinogradova12, Valentina N. Sorotskaya13, Larisa Yu. Shirokova14,15
1Nasonova Research Institute of Rheumatology, Moscow, Russia; 2Pirogov Russian National Research Medical University, Moscow, Russia; 3Mechnikov North-Western State Medical University, Saint Petersburg, Russia; 4Clinical Rheumatology Hospital No. 25, Saint Petersburg, Russia; 5Medical and Sanitary Unit No. 157 LLC, Saint Petersburg, Russia; 6Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia; 7Meili LLC, Saint Petersburg, Russia; 8Research Center “Eco-safety” LLC, Saint Petersburg, Russia; 9Health Energy LLC, Saint Petersburg, Russia; 10Zvezdnaya Clinic LLC, Saint Petersburg, Russia; 11Kazan State Medical University, Kazan, Russia; 12Ulyanovsk Regional Clinical Hospital, Ulyanovsk, Russia; 13Tula State University, Tula, Russia; 14Yaroslavl State Medical University, Yaroslavl, Russia; 15Institute of Professional Training, Yaroslavl, Russia
*nat-kash@yandex.ru