Обзор обновленных клинических рекомендаций по лечению больных остеоартритом: фокус на локальные формы нестероидных противовоспалительных препаратов

Погожева Е.Ю., Амирджанова В.Н., Каратеев А.Е. Обзор обновленных клинических рекомендаций по лечению больных остеоартритом: фокус на локальные формы нестероидных противовоспалительных препаратов. Consilium Medicum. 2020; 22 (9): 76–81. DOI: 10.26442/20751753.2020.9.200396

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Pogozheva E.Iu., Amirdzhanova V.N., Karateev A.E. Review of updated clinical guidelines for the treatment of patients with osteoarthritis: focus on the topical nonsteroidal anti-inflammatory drugs. Consilium Medicum. 2020; 22 (9): 76–81. DOI: 10.26442/20751753.2020.9.200396

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Аннотация

Остеоартрит (ОА) – хроническое прогрессирующее заболевание, обычно поражающее кисти, коленные и тазобедренные суставы, вызывающее выраженную боль и значительно снижающее качество жизни пациентов. Локальные формы нестероидных противовоспалительных препаратов (НПВП) широко представлены в международных рекомендациях в качестве первого шага противовоспалительной терапии ОА. Так, Американский колледж ревматологии (ACR) настоятельно рекомендует топические НПВП пациентам с ОА коленного сустава и условно – пациентам с ОА суставов кистей. В соответствии с принципом, что предпочтительны препараты с наименьшим системным воздействием, местные НПВП являются первым шагом противовоспалительной терапии при ОА указанных локализаций. Кроме того, ACR рекомендует людям в возрасте 75 лет и старше использовать местные, а не пероральные НПВП; пожилые пациенты часто имеют сопутствующие заболевания и/или повышенный риск развития сердечно-сосудистых, желудочно-кишечных или почечных осложнений. Международное общество по изучению остеоартрита (OARSI) относит применение локальных форм НПВП к рекомендациям самого высокого уровня (1А). Данный метод настоятельно рекомендован пациентам с ОА коленного сустава без сопутствующих заболеваний и с сопутствующими заболеваниями желудочно-кишечного тракта или сердечно-сосудистой системы. Местные НПВП рекомендованы более настоятельно, чем все пероральные анальгетики, из-за благоприятного баланса эффективности и переносимости.

Ключевые слова: остеоартрит, клинические рекомендации, лечение, локальные формы нестероидных противовоспалительных препаратов, эффективность, переносимость.

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Osteoarthritis (OA) is a chronic, progressive disease that usually affects the hands, knee and hip joints, causing severe pain and significantly reducing the quality of life of patients. Topical non-steroidal anti-inflammatory drugs (NSAIDs) are widely represented in international guidelines as the first step of anti-inflammatory therapy for OA. Thus, the American College of Rheumatology (ACR) strongly recommends topical NSAIDs for patients with knee OA and conventionally for patients with hand OA. In accordance with the principle that drugs with the least systemic effect are preferred, topical NSAIDs are the first step in anti-inflammatory therapy for OA of these localizations. In addition, ACR recommends that people age 75 and older use topical rather than oral NSAIDs; elderly patients often have comorbidities and/or an increased risk for cardiovascular, gastrointestinal, or renal complications. The Osteoarthritis Research Society International (OARSI) classifies the use of topical NSAIDs as a recommendation of the highest level (1A). This method is strongly recommended for patients with knee OA without concomitant diseases and with concomitant diseases of the gastrointestinal tract or cardiovascular system. Topical NSAIDs are recommended more strongly than all oral analgesics due to their favorable balance of efficacy and tolerability.

Key words: osteoarthritis, clinical guidelines, treatment, topical non-steroidal anti-inflammatory drugs, efficacy, tolerance.

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Список литературы

1. Ревматология. Клинические рекомендации. Под ред. Е.Л.Насонова. М.: ГЭОТАР-Медиа, 2017; с. 240.
[Rheumatology. Clinical guidelines. Ed. E.L.Nasonova. Moscow: GEOTAR-Media, 2017; p. 240 (in Russian).]
2. Kolasinski LS, Neogi T, Hochberg CM et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care and Research. 2020; 72: 1–14. DOI: 10.1002/acr.24131
3. Bannuru RR, Osani MC, Vaysbrot EE et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 2019; 27 (11): 1578–89. DOI: 10.1016/j.joca.2019.06.011
4. McAlindon TE, LaValley MP, Harvey WF et al. Effect of intra‐articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial. JAMA 2017; 317: 1967–75.
5. Da Costa BR, Reichenbach S, Keller N 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
6. Busse JW, Wang L, Kamaleldin M et al. Opioids for chronic noncancer pain: a systematic review and meta‐analysis. JAMA 2018; 320: 2448–60.
7. Zhang W, Doherty M. Efficacy paradox and proportional contextual effect (PCE). Clin Immunol 2018; 186: 82–6.
8. Underwood M, Ashby D, Carnes D et al. Topical or oral ibuprofen for chronic knee pain in older people. Health Technol Assess 2008; 12 (22): III–IV, IX–155.
9. Nissen SE, Yeomans ND, Solomon DH et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med 2016; 375 (26): 2519–29.
10. Trelle S, Reichenbach S, Wandel S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 2011; 342: c7086.
11. Scanzello CR. Role of low-grade inflammation in osteoarthritis. Curr Opin Rheumatol 2017; 29 (1): 79–85. DOI: 10.1097/BOR.000000000000035
12. Robinson WH, Lepus CM, Wang Q et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016; 12 (10): 580–92. DOI: 10.1038/nrrheum.2016.136. Epub 2016 Aug 19.
13. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res Ther 2017; 19 (1): 18. DOI: 10.1186/s13075-017-1229-9
14. Chou R, McDonagh MS, Nakamoto E, Griffin J. Analgesics for osteoarthritis: an update of the 2006 comparative effectiveness review. Rockville, MD. http://www.ncbi.nlm.nih.gov/pubmedhealth/
PMH0016485/pdf/TOC.pdf
15. Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non-steroidal antiinflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. Br Med J 2004; 329: 324.
16. Tugwell PS, Wells GA, Shainhouse JZ. Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. J Rheumatol 2004; 31: 2002–12.
17. Simon LS, Grierson LM, Naseer Z et al. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 2009; 143: 238–45.
18. Towheed TE. Pennsaid therapy for osteoarthritis of the knee: a systematic review and metaanalysis of randomized controlled trials. J Rheumatol 2006; 33: 567–73.
19. Baer PA, Thomas LM, Shainhouse Z. Treatment of osteoarthritis of the knee with a topical diclofenac solution: a randomised controlled, 6-week trial [ISRCTN53366886]. BMC Musculoskelet Dis 2005; 6: 44.
20. Bookman AA, Williams KS, Shainhouse JZ. Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: a randomized controlled trial. Can Med Assoc J 2004; 171: 333–8.
21. Underwood M, Ashby D, Cross P et al. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study. Br Med J 2008; 336: 138–42.
22. Derry S, Conaghan P, Da Silva JAP et al. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev 2012; 9: CD007400.
23. Rannou F, Pelletier JP, Martel-Pelletier J. Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum 2016; 45
(4 Suppl.): S18–S21. DOI: 10.1016/j.semarthrit.2015.11.007
24. Zeng C, Wei J, Persson MSM et al. Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies. Br J Sports Med 2018; 52: 642–50.
25. Honvo G, Leclercq V, Geerinck A et al. Safety of Topical Non‑steroidal Anti‑Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta‑Analysis. Drugs Aging 2019; 36 (Suppl. 1): S45–S64. DOI: 10.1007/s40266-019-00661-0
26. Altman RD, Dreiser RL, Fisher CL et al. Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial. J Rheumatol 2009; 36 (9): 1991–9. DOI: 10.3899/jrheum.081316
27. Baraf HS, Gold MS, Clark MB, Altman RD. Safety and efcacy of topical diclofenac sodium 1% gel in knee osteoarthritis: a randomized controlled trial. Phys Sportsmed 2010; 38 (2): 19.
28. Barthel HR, Haselwood D, Longley S et al. Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis. Semin Arthritis Rheum. 2009; 39 (3): 203.
29. Bruhlmann P, Michel BA. Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double-blind, controlled clinical trial. Clin Exp Rheumatol 2003; 21 (2): 193–8.
30. Dreiser RL, Tisne-Camus M. DHEP plasters as a topical treatment of knee osteoarthritis – a double-blind placebo-controlled study. Drugs Exp Clin Res 1993; 19 (3): 117.
31. Niethard F, Gold MS, Solomon GS et al. Efcacy of topical diclofenac diethylamine gel in osteoarthritis of the knee. J Rheumatol 2005; 32 (12): 2384.
32. Conaghan PG, Dickson J, Bolten W et al. A multicentre, randomized, placebo- and active-controlled trial comparing the efcacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis. Rheumatology (Oxf) 2013; 52 (7): 1303–12. DOI: 10.1093/rheum atology/ket133
33. Kneer W, Rother M, Mazgareanu S, Seidel EJ, European Idea Study Group. A 12-week randomized study of topical therapy with three dosages of ketoprofen in Transfersome gel (IDEA-033) compared with the ketoprofen-free vehicle (TDT 064), in patients with osteoarthritis of the knee. J Pain Res 2013; 6 (101540514): 743–53. DOI: 10.2147/JPR.S51054
34. Rother M, Lavins BJ, Kneer W et al. Efcacy and safety of epicutaneous ketoprofen in Transfersome (IDEA-033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial. Ann Rheum Dis 2007; 66 (9): 1178–83. DOI: 10.1136/ard.2006.065128
35. Rother M, Conaghan PG. A randomized, double-blind, phase III trial in moderate osteoarthritis knee pain comparing topical ketoprofen gel with ketoprofen-free gel. J Rheumatol 2013; 40 (10): 1742–8. DOI: 10.3899/jrheum.130192
36. Rovensky J, Micekova D, Gubzova Z et al. Treatment of knee osteoarthritis with a topical non-steroidal antiinfammatory drug. Results of a randomized, double-blind, placebo-controlled study on the efficacy and safety of a 5% ibuprofen cream. Drugs Exp Clin Res 2001; 27 (5–6): 209.
37. Trnavský K, Fischer M, Vogtle-Junkert U, Schreyger F. Efcacy and safety of 5% ibuprofen cream treatment in knee osteoarthritis. Results of a randomized, double-blind, placebo-controlled study. J Rheumatol 2004; 31 (3): 565.
38. Varadi G, Zhu Z, Blattler T et al. Randomized clinical trial evaluating transdermal ibuprofen for moderate to severe knee osteoarthritis. Pain Phys 2013; 16 (6): E749.
39. Allegrini A, Nuzzo L, Pavone D et al. Efcacy and safety of piroxicam patch versus piroxicam cream in patients with lumbar osteoarthritis. A randomized, placebo-controlled study. Arzneimittelforschung 2009; 59 (8): 403–9.
40. Ergün H, Kulcu D, Kutlay S et al. Efcacy and safety of topical nimesulide in the treatment of knee osteoarthritis. J Clin Rheumatol 2007; 13 (5): 251.
41. Pelletier JP, Martel-Pelletier J, Rannou F, Cooper C. Efficacy and safety of oral NSAIDs and analgesics in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum 2016; V45 (Suppl. 4): S22–S27. DOI: 10.1016/j.semarthrit.2015.11.009

________________________________________________

1. Rheumatology. Clinical guidelines. Ed. E.L.Nasonova. Moscow: GEOTAR-Media, 2017; p. 240 (in Russian).
2. Kolasinski LS, Neogi T, Hochberg CM et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care and Research. 2020; 72: 1–14. DOI: 10.1002/acr.24131
3. Bannuru RR, Osani MC, Vaysbrot EE et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 2019; 27 (11): 1578–89. DOI: 10.1016/j.joca.2019.06.011
4. McAlindon TE, LaValley MP, Harvey WF et al. Effect of intra‐articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial. JAMA 2017; 317: 1967–75.
5. Da Costa BR, Reichenbach S, Keller N 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
6. Busse JW, Wang L, Kamaleldin M et al. Opioids for chronic noncancer pain: a systematic review and meta‐analysis. JAMA 2018; 320: 2448–60.
7. Zhang W, Doherty M. Efficacy paradox and proportional contextual effect (PCE). Clin Immunol 2018; 186: 82–6.
8. Underwood M, Ashby D, Carnes D et al. Topical or oral ibuprofen for chronic knee pain in older people. Health Technol Assess 2008; 12 (22): III–IV, IX–155.
9. Nissen SE, Yeomans ND, Solomon DH et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med 2016; 375 (26): 2519–29.
10. Trelle S, Reichenbach S, Wandel S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 2011; 342: c7086.
11. Scanzello CR. Role of low-grade inflammation in osteoarthritis. Curr Opin Rheumatol 2017; 29 (1): 79–85. DOI: 10.1097/BOR.000000000000035
12. Robinson WH, Lepus CM, Wang Q et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016; 12 (10): 580–92. DOI: 10.1038/nrrheum.2016.136. Epub 2016 Aug 19.
13. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res Ther 2017; 19 (1): 18. DOI: 10.1186/s13075-017-1229-9
14. Chou R, McDonagh MS, Nakamoto E, Griffin J. Analgesics for osteoarthritis: an update of the 2006 comparative effectiveness review. Rockville, MD. http://www.ncbi.nlm.nih.gov/pubmedhealth/
PMH0016485/pdf/TOC.pdf
15. Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non-steroidal antiinflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. Br Med J 2004; 329: 324.
16. Tugwell PS, Wells GA, Shainhouse JZ. Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. J Rheumatol 2004; 31: 2002–12.
17. Simon LS, Grierson LM, Naseer Z et al. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 2009; 143: 238–45.
18. Towheed TE. Pennsaid therapy for osteoarthritis of the knee: a systematic review and metaanalysis of randomized controlled trials. J Rheumatol 2006; 33: 567–73.
19. Baer PA, Thomas LM, Shainhouse Z. Treatment of osteoarthritis of the knee with a topical diclofenac solution: a randomised controlled, 6-week trial [ISRCTN53366886]. BMC Musculoskelet Dis 2005; 6: 44.
20. Bookman AA, Williams KS, Shainhouse JZ. Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: a randomized controlled trial. Can Med Assoc J 2004; 171: 333–8.
21. Underwood M, Ashby D, Cross P et al. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study. Br Med J 2008; 336: 138–42.
22. Derry S, Conaghan P, Da Silva JAP et al. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev 2012; 9: CD007400.
23. Rannou F, Pelletier JP, Martel-Pelletier J. Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum 2016; 45
(4 Suppl.): S18–S21. DOI: 10.1016/j.semarthrit.2015.11.007
24. Zeng C, Wei J, Persson MSM et al. Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies. Br J Sports Med 2018; 52: 642–50.
25. Honvo G, Leclercq V, Geerinck A et al. Safety of Topical Non‑steroidal Anti‑Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta‑Analysis. Drugs Aging 2019; 36 (Suppl. 1): S45–S64. DOI: 10.1007/s40266-019-00661-0
26. Altman RD, Dreiser RL, Fisher CL et al. Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial. J Rheumatol 2009; 36 (9): 1991–9. DOI: 10.3899/jrheum.081316
27. Baraf HS, Gold MS, Clark MB, Altman RD. Safety and efcacy of topical diclofenac sodium 1% gel in knee osteoarthritis: a randomized controlled trial. Phys Sportsmed 2010; 38 (2): 19.
28. Barthel HR, Haselwood D, Longley S et al. Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis. Semin Arthritis Rheum. 2009; 39 (3): 203.
29. Bruhlmann P, Michel BA. Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double-blind, controlled clinical trial. Clin Exp Rheumatol 2003; 21 (2): 193–8.
30. Dreiser RL, Tisne-Camus M. DHEP plasters as a topical treatment of knee osteoarthritis – a double-blind placebo-controlled study. Drugs Exp Clin Res 1993; 19 (3): 117.
31. Niethard F, Gold MS, Solomon GS et al. Efcacy of topical diclofenac diethylamine gel in osteoarthritis of the knee. J Rheumatol 2005; 32 (12): 2384.
32. Conaghan PG, Dickson J, Bolten W et al. A multicentre, randomized, placebo- and active-controlled trial comparing the efcacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis. Rheumatology (Oxf) 2013; 52 (7): 1303–12. DOI: 10.1093/rheum atology/ket133
33. Kneer W, Rother M, Mazgareanu S, Seidel EJ, European Idea Study Group. A 12-week randomized study of topical therapy with three dosages of ketoprofen in Transfersome gel (IDEA-033) compared with the ketoprofen-free vehicle (TDT 064), in patients with osteoarthritis of the knee. J Pain Res 2013; 6 (101540514): 743–53. DOI: 10.2147/JPR.S51054
34. Rother M, Lavins BJ, Kneer W et al. Efcacy and safety of epicutaneous ketoprofen in Transfersome (IDEA-033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial. Ann Rheum Dis 2007; 66 (9): 1178–83. DOI: 10.1136/ard.2006.065128
35. Rother M, Conaghan PG. A randomized, double-blind, phase III trial in moderate osteoarthritis knee pain comparing topical ketoprofen gel with ketoprofen-free gel. J Rheumatol 2013; 40 (10): 1742–8. DOI: 10.3899/jrheum.130192
36. Rovensky J, Micekova D, Gubzova Z et al. Treatment of knee osteoarthritis with a topical non-steroidal antiinfammatory drug. Results of a randomized, double-blind, placebo-controlled study on the efficacy and safety of a 5% ibuprofen cream. Drugs Exp Clin Res 2001; 27 (5–6): 209.
37. Trnavský K, Fischer M, Vogtle-Junkert U, Schreyger F. Efcacy and safety of 5% ibuprofen cream treatment in knee osteoarthritis. Results of a randomized, double-blind, placebo-controlled study. J Rheumatol 2004; 31 (3): 565.
38. Varadi G, Zhu Z, Blattler T et al. Randomized clinical trial evaluating transdermal ibuprofen for moderate to severe knee osteoarthritis. Pain Phys 2013; 16 (6): E749.
39. Allegrini A, Nuzzo L, Pavone D et al. Efcacy and safety of piroxicam patch versus piroxicam cream in patients with lumbar osteoarthritis. A randomized, placebo-controlled study. Arzneimittelforschung 2009; 59 (8): 403–9.
40. Ergün H, Kulcu D, Kutlay S et al. Efcacy and safety of topical nimesulide in the treatment of knee osteoarthritis. J Clin Rheumatol 2007; 13 (5): 251.
41. Pelletier JP, Martel-Pelletier J, Rannou F, Cooper C. Efficacy and safety of oral NSAIDs and analgesics in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum 2016; V45 (Suppl. 4): S22–S27. DOI: 10.1016/j.semarthrit.2015.11.009

Авторы

Е.Ю. Погожева*, В.Н. Амирджанова, А.Е. Каратеев

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия
*dr.pogozheva@gmail.com

________________________________________________

Elena Iu. Pogozheva*, Vera N. Amirdzhanova, Andrey E. Karateev

Nasonova Research Institute of Rheumatology, Moscow, Russia
*dr.pogozheva@gmail.com

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