Роль лабораторных биомаркеров в мониторинге эффективности терапии биоаналогом ритуксимаба (Ацеллбия, «БИОКАД») у больных ревматоидным артритом
Роль лабораторных биомаркеров в мониторинге эффективности терапии биоаналогом ритуксимаба (Ацеллбия, «БИОКАД») у больных ревматоидным артритом
Авдеева А.С., Черкасова М.В., Кусевич Д.А. и др. Роль лабораторных биомаркеров в мониторинге эффективности терапии биоаналогом ритуксимаба (Ацеллбия, «БИОКАД») у больных ревматоидным артритом. Терапевтический архив. 2019; 91 (5): 26–33. DOI: 10.26442/00403660.2019.05.000230
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Аннотация
Цель: оценить роль лабораторных биомаркеров в мониторинге эффективности терапии биоаналогом ритуксимаба (РТМ) в суммарной дозе 1200 мг.
Материалы и методы. Обследовано 20 больных с достоверным диагнозом ревматоидного артрита (РА; 18 женщин, медиана возраста 61,5 [54–66,5] лет, длительность заболевания 39,5 [20–84] лет, индекс DAS28 5,6 [4,9–6,8]). Всем больным проведено по 2 инфузии РТМ (Ацеллбия®) в дозе 600 мг внутривенно с интервалом в 2 нед на фоне терапии метотрексатом (МТ), нестероидными противовоспалительными препаратами (НПВП) и глюкокортикоидами (ГК). Клинические и лабораторные показатели анализировали непосредственно перед началом терапии, а затем через 12 и 24 нед после первой инфузии препарата.
Результаты. У ответчиков на терапию индекс DAS28, скорость оседания эритроцитов и уровень С-реактивного белка достоверно снижались через 12 и 24 нед после применения РТМ. Снижение концентрации иммуноглобулина (Ig) M ревматоидного фактора (РФ) в сыворотках ответчиков выявлено на 12-й и 24-й неделе и составило 79,7 и 87,1% от исходного уровня соответственно (p<0,05). Уровень IgA РФ снижался на 72 и 85% от исходного уровня соответственно на 12-й и 24-й неделе терапии РТМ у больных с хорошим эффектом препарата (p<0,05). Концентрация антител к циклическому цитруллинированному пептиду в сыворотках ответчиков оставалась высокой на всем протяжении наблюдения. Деплеция CD19+ В-лимфоцитов достигнута к 12-й неделе терапии у всех пациентов (абсолютное содержание 0), к 24-й неделе отмечено нарастание уровня CD19+ B-клеток (0,0030 [0,0003–0,0270] 109/л). Средние уровни иммуноглобулинов как в группе пациентов с хорошим, так и с удовлетворительным эффектом оставались в пределах нормы. Применение ацеллбии также сопровождалось быстрым и выраженным снижением концентрации практически всего спектра показателей цитокинового профиля через 12–24 нед после первой инфузии.
Заключение. Анализ иммунологических эффектов биоаналога РТМ свидетельствует о его способности вызывать снижение лабораторных показателей воспалительной активности, концентрации аутоантител, провоспалительных цитокинов, хемокинов и факторов роста, полную деплецию В-лимфоцитов. Серопозитивность по IgM РФ и/или антителам к цитруллинированным белкам и повышенные уровни данных аутоантител в сыворотке крови, а также повышенный уровень интерлейкина-17 через 12 нед лечения можно рассматривать в качестве предикторов хорошего ответа на проводимую терапию.
Ключевые слова: ревматоидный артрит, биоаналог ритуксимаба, активность заболевания, аутоантитела, цитокиновый профиль, В-лимфоциты.
Materials and methods. 20 patients (pts) with rheumatoid arthritis (RA) (18 woman, mean age 61.5(54–66.5) years, mean disease duration 39.5(20–84) months, mean DAS28 5.6(4.9–6.8)) received two intravenous RTM biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and weeks 12 and 24 after the first infusion of RTX.
Results. RTM biosimilar induced decreases in DAS28, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) at week 12 and 24, p<0.05. The decrease in the concentration of immunoglobulin (Ig) M rheumatoid factor (RF) was detected at week 12 and 24 and amounted to 79.7% and 87.1% of the initial level, respectively (p<0.05). IgA RF level decreased by 72% and 85% from baseline, respectively, at the 12 and 24 week of RTM therapy in patients with a good effect of the drug (p<0.05). The concentration of antibodies to cyclic citrullinated peptide in the sera did not reduced. Depletion of CD19+ B-cells was achieved at week 12 in all patients (absolute number 0), with an increase in the level of B-cells at week 24 (0.0030 (0.0003–0.0270) 109/l). The immunoglobulin level decreased at week 24, but remained normal. RTM biosimilar therapy was accompanied by a rapid and pronounced decrease in the concentration of cytokine profile by 12–24 weeks after the first infusion.
Conclusion. RTX biosimilar therapy induced a rapid and significant improvement in ESR, CRP, IgM/IgA RF, anti-MCV, proinflammatory cytokines, chemokines and growth factors levels and CD19+ B-cells depletion in RA pts. IgM RF and/or antibodies to citrullinated proteins seropositivity, increased levels of interleukin-17 after 12 weeks of treatment can be considered as predictors of a good response to RTM biosimilar therapy.
Keywords: rheumatoid arthritis, rituximab biosimilar, disease activity, autoantibodies, cytokine profile, B-lymphocytes.
Материалы и методы. Обследовано 20 больных с достоверным диагнозом ревматоидного артрита (РА; 18 женщин, медиана возраста 61,5 [54–66,5] лет, длительность заболевания 39,5 [20–84] лет, индекс DAS28 5,6 [4,9–6,8]). Всем больным проведено по 2 инфузии РТМ (Ацеллбия®) в дозе 600 мг внутривенно с интервалом в 2 нед на фоне терапии метотрексатом (МТ), нестероидными противовоспалительными препаратами (НПВП) и глюкокортикоидами (ГК). Клинические и лабораторные показатели анализировали непосредственно перед началом терапии, а затем через 12 и 24 нед после первой инфузии препарата.
Результаты. У ответчиков на терапию индекс DAS28, скорость оседания эритроцитов и уровень С-реактивного белка достоверно снижались через 12 и 24 нед после применения РТМ. Снижение концентрации иммуноглобулина (Ig) M ревматоидного фактора (РФ) в сыворотках ответчиков выявлено на 12-й и 24-й неделе и составило 79,7 и 87,1% от исходного уровня соответственно (p<0,05). Уровень IgA РФ снижался на 72 и 85% от исходного уровня соответственно на 12-й и 24-й неделе терапии РТМ у больных с хорошим эффектом препарата (p<0,05). Концентрация антител к циклическому цитруллинированному пептиду в сыворотках ответчиков оставалась высокой на всем протяжении наблюдения. Деплеция CD19+ В-лимфоцитов достигнута к 12-й неделе терапии у всех пациентов (абсолютное содержание 0), к 24-й неделе отмечено нарастание уровня CD19+ B-клеток (0,0030 [0,0003–0,0270] 109/л). Средние уровни иммуноглобулинов как в группе пациентов с хорошим, так и с удовлетворительным эффектом оставались в пределах нормы. Применение ацеллбии также сопровождалось быстрым и выраженным снижением концентрации практически всего спектра показателей цитокинового профиля через 12–24 нед после первой инфузии.
Заключение. Анализ иммунологических эффектов биоаналога РТМ свидетельствует о его способности вызывать снижение лабораторных показателей воспалительной активности, концентрации аутоантител, провоспалительных цитокинов, хемокинов и факторов роста, полную деплецию В-лимфоцитов. Серопозитивность по IgM РФ и/или антителам к цитруллинированным белкам и повышенные уровни данных аутоантител в сыворотке крови, а также повышенный уровень интерлейкина-17 через 12 нед лечения можно рассматривать в качестве предикторов хорошего ответа на проводимую терапию.
Ключевые слова: ревматоидный артрит, биоаналог ритуксимаба, активность заболевания, аутоантитела, цитокиновый профиль, В-лимфоциты.
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Materials and methods. 20 patients (pts) with rheumatoid arthritis (RA) (18 woman, mean age 61.5(54–66.5) years, mean disease duration 39.5(20–84) months, mean DAS28 5.6(4.9–6.8)) received two intravenous RTM biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and weeks 12 and 24 after the first infusion of RTX.
Results. RTM biosimilar induced decreases in DAS28, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) at week 12 and 24, p<0.05. The decrease in the concentration of immunoglobulin (Ig) M rheumatoid factor (RF) was detected at week 12 and 24 and amounted to 79.7% and 87.1% of the initial level, respectively (p<0.05). IgA RF level decreased by 72% and 85% from baseline, respectively, at the 12 and 24 week of RTM therapy in patients with a good effect of the drug (p<0.05). The concentration of antibodies to cyclic citrullinated peptide in the sera did not reduced. Depletion of CD19+ B-cells was achieved at week 12 in all patients (absolute number 0), with an increase in the level of B-cells at week 24 (0.0030 (0.0003–0.0270) 109/l). The immunoglobulin level decreased at week 24, but remained normal. RTM biosimilar therapy was accompanied by a rapid and pronounced decrease in the concentration of cytokine profile by 12–24 weeks after the first infusion.
Conclusion. RTX biosimilar therapy induced a rapid and significant improvement in ESR, CRP, IgM/IgA RF, anti-MCV, proinflammatory cytokines, chemokines and growth factors levels and CD19+ B-cells depletion in RA pts. IgM RF and/or antibodies to citrullinated proteins seropositivity, increased levels of interleukin-17 after 12 weeks of treatment can be considered as predictors of a good response to RTM biosimilar therapy.
Keywords: rheumatoid arthritis, rituximab biosimilar, disease activity, autoantibodies, cytokine profile, B-lymphocytes.
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42. Smallie T, et al. IL-10 inhibits transcription elongation of the human TNF gene in primary macrophages. J Exp Med. 2010;207:2081-8. doi.org/10.1084/jem.20100414
43. vanRoon J, et al. Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. J Rheumatol. 2003;30:648-51.
44. Wong CK, et al. Effects of inflammatory cytokine IL-27 on the activation of fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Res Ther. 2010;12:R129. doi.org/10.1186/ar3067
45. Emery P, Fleishmann R, Filipowicz-Sosnowska A, et al. For the DANCER Study group. The Efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment. Results of a phase IIb randomized, double-blind, placebo-controlled dose-range trial. Arthritis Rheum. 2006;54:1390-400. doi.org/10.1002/art.21778
46. Emery P, Deodhar A, Rigby W, et al. Efficacy and Safety of different doses and retreatment of Rituximab: a randomized, placebo-controlled trial in patients who are biologically naïve with active rheumatoid arthritis and anadequate response to methotrexate (Study Evaluating Rituximab`s Efficacy in MTX inadequate responders (SERENA). Ann Rheum Dis. 2010;69:1629-35. doi.org/10.1136/ard.20 09.119933
47. Rubbert-Roth A, Tak P, Zebrini C, et al. Efficacy and safety of various repeat treatment dosing regimes in Rituximab in patients with active rheumatoid arthritis: results of a phase III randomized study (MIRROR) dosing regimens of rituximab in patients with active RA: results of a phase III randomized study (MIRROR). Rheumatology. 2010;49:1683-93. doi.org/10.1093/rheumatology/keq401
48. Roll P, Dorner T, Tony H-P. Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment. Arthritis Rheum. 2008;58:1566-75. doi.org/10.1002/art.23473
49. van Vollenhoven RF, Emery P, Bingham CO, et al. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol. 2010;37:558-67. doi.org/10.3899/jrheum.090856
50. Mariette X, Kivitz A, Isaacs J, et al. Effectiveness of Rituximab (RTX) + methotrexate (MTX) in patients (pts) with early active rheumatoid arthritis (RA) and disease charaxteristics associated with poor outcomes. Arthritis Rheum. 2009;60 (Suppl):631.
51. Tak P, Cohen S, Emery P, et al. Baseline autoantibody status (RF, ant-CCP) and clinical response following the first treatment course with rituximab. Arthritis Rheum. 2006;54(Suppl 9):368.
52. Tak P, Rigby W, Rubbert-Roth A. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70:39-46. doi.org/10.1136/ard.2010.137703
53. Khan A, Mahmud T, Hammond T, et al. Rituximab (RTX) is more effective in active sero-positive RA than sero-negative RA. Arthritis Rheum. 2010;62(Suppl 10):1830.
54. Isaacs JD, Olech E, Tak PP, et al. Autoantibody-positive rheumatoid arthritis patients have enchanced clinical response when compared with seronegative patients. Ann Rheum Dis. 2009;68(Suppl 3):442.
55. Silverman G, Schwartzman S, Townsend M, et al. Identification of biomarkers for enhanced benefit to Rituximab in rheumatoid arthritis: role for autoantibodies and inflammatory markers. Arthritis Rheum. 2009;60(Suppl.):628.
56. Sellam J, Hendel-Chavez H, Rouanet S, et al. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011;63:933-8. doi.org/ 10.1002/art.30233
57. Thurling R, Boumans M, Vos K, et al. Early changes in serum levels of cytokines and chemokines are predictive of the response to Rituximab treatment in rheumatoid arthritis. Arthritis Rheum. 2009;60(Suppl.):630.
2. Nasonov EL. Rituximab. V kn.: Genno-inzhenernyebiologicheskiepreparaty v lecheniirevmatoidnogoartrita. Pod red. E.L. Nasonova Edited by EL. Nasonov. Moscow: IMA-PRESS, 2013:200-221 (In Russ.).
3. Huscher D, Mittendorf T, von Hinuber U, et al. Evolution of cost structures in rheumatoid arthritis over the past decade. Ann Rheum Dis. 2015;74(4):738-45. doi.org/10.1136/annrheumdis-2013-204311
4. Nasonov EL. Biosimilars in rheumatology. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(6):628-40 (In Russ.). doi: 10.14412/1995-4484-2016-628-640
5. Federal law of December 22, 2014 № 429-FZ «On Amendments to the Federal Law "On Circulation of Medicines"». Adopted by the State Duma on December 9, 2014 Approved by the Federation Council December 17, 2014 (In Russ.).
6. Yoo DH, Suh CH, Shim SC, Jeka S, Molina FFC, Hrycaj P, Wiland P, Lee EY, Medina-Rodriguez FG, Shesternya P, Radominski S, Stanislav M, et all. Efficacy, Safety and Pharmacokinetics of Up to Two Courses of the Rituximab Biosimilar CT-P10 Versus Innovator Rituximab in Patients with Rheumatoid Arthritis: Results up to Week 72 of a Phase I Randomized Controlled Trial. Bio Drugs. 2017 Aug;31(4):357-67. doi: 10.1007/s40259-017-0232-7
7. Park W, Suh CH, Shim SC, et al. Efficacy and safety of switching from innovator rituximab to biosimilar CT-P10 compared with continued treatment with CT-P10: results of a 56-week open-label study in patients with rheumatoid arthritis. Bio Drugs. 2017 Jun 9; doi:10.1007/s40259-017-0233-6 [Epub ahead of print]
8. Yoo DH, Suh CH, Shim SC, Jeka S, Cons-Molina FF, Hrycaj P, Wiland P, Lee EY, Medina-Rodriguez FG, Shesternya P, Radominski S, Stanislav M, Kovalenko V, Sheen DH, Myasoutova L, Lim MJ, Choe JY, Lee SJ, Lee SY, Kwon TS, Park W. A multicentrerandomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Mar;76(3):566-70. doi: 10.1136/annrheumdis-2016-209540 Epub 2016 Sep 13.
9. Nasonov EL, Zonova EV, Ivanova ON, et al. The results of a phase III comparative clinical trial of rituximab (Acellbia® and MabThera®) in rheumatoid arthritis (the BIORA study). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(5):510-9 (In Russ.). https://doi.org/10.14412/1995-4484-2016-510-519
10. Bredemeier M, de Oliveira FK, Rocha CM. Low-versus High-dose rituximab for rheumatoid arthritis: a systemic review and metaanalysis. Arthritis Care Res. 2014;66:228-35. https://doi.org/10.1002/acr.22116
11. Buch MH, Smolen JS, Betteridge N, et al. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70:909-20. doi: 10.1136/ard.2010.144998
12. Sacco JJ, Botten J, Macbeth F, Bagust A, Clark P. The Average Body Surface Area of Adult Cancer Patients in the UK: A Multicentre Retrospective Study. PLoS ONE. 2010;5(1):e8933. doi: 10.1371/journal.pone.0008933
13. Nasonov EL, Mazurov VI, Zonova EV, Knyazeva LA, Marusenko IM, et all. The efficacy and safety of rituximab biosimilar (Acellbia®) in rheumatoid arthritis as the first biological agent: results of phase iii (ALTERRA) clinical trial. Rheumatology Science and Practice. 2017;55(4):351-9 (In Russ.). https://doi.org/10.14412/1995-4484-2017-351-359
14. Cornec D, Avouac J, Youinou P, Saraux A. Critical analysis of rituximab-induced serological changes in connective tissue diseases. Autoimmun Rev. 2009;8:515-19. doi: 10.1016/j.autrev.2009.01.007
15. Grosjean C, de Chaisemartin L, Nicaise-Roland P, et al. Prospective cohort study of rituximab effects on rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis. Ann Rheum Dis. 2008;67(Suppl II):196.
16. Aleksandrova EN, Avdeyeva AS, Lukina GV, Novikov AA, Cherkasova MV, Popkova TV, Lineva OG, Kuzikyants GK, Nasonov EL. The clinical and immunological effects of anti-b-cell therapy in patients with rheumatoid arthritis. Rheumatology Science and Practice. 2012;50(1):14-21 (In Russ.) https://doi.org/ 10.14412/1995-4484-2012-498
17. Cambridge G, Stohl W, Leandro MJ, et al. Circulating levels of Blymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationship with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum. 2006;54:723-32. doi: 10.1002/art.21650
18. Cohen S, Emery P, Greenwald M, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Results of multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54:2793-806. https://doi.org/10.1002/art. 22025
19. Higashida J, Wun T, Schmidt S. Safety and Efficacy of Rituximab in Patients with Rheumatoid Arthritis Refractory to Disease Modifying Antirheumatic Drugs and Anti-Tumor Necrosis Factor-a Treatment. Rheumatology. 2005;32:2109-15.
20. Tsiakalos A, Avgoustidis N, Moutsopoulos H. Rituximab therapy in Greek patients with rheumatoid arthritis. Biologics: Targets & Therapy. 2008;2:911-6. https://doi. org/10.2147/BTT.S3939
21. Bokarewa M, Lindholm C, Zendjanchi K, et al. Efficacy of Anti-CD20 treatment in patients with rheumatoid arthritis resistant to a combination of methotrexate/anti-TNF therapy. Scand J Immunol. 2007;66:467-83. https://doi.org/10.1111/j.1365-3083.2007.01995.x
22. Toubi E, Kesser A, Slobodin G, et al. Macrophage function changes following rituximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66: 818-20. https://doi.org/10.1136/ard.2006.062505
23. Vizioli C, Viana V, Ribeiro A. Auto-antibody titers for monitoring rituximab therapy in rheumatoid arthritis. Ann Rheum Dis. 2012;71(Suppl 3):667.
24. Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med. 2013;5:178ra 40. doi: 10.1126/scitranslmed.3005580
25. Aletaha D, Blüml S. Therapeutic implications of autoantibodies in rheumatoid arthritis. RMD Open. 2016;(2):e000009. doi: 10.1136/rmdopen-2014-000009
26. Harre U, Georgess D, Bang H, et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest. 2012;122:1791-802. doi: 10.1172/JCI60975
27. Harre U, Lang SC, Pfeifle R, et al. Glycosylation of immunoglobulin G determines osteoclast differentiation and bone lose. Nat Communocation. 2015. doi: 10.1038/ ncomms7651
28. Nasonov EL. Problems of rheumatoid arthritis immunopathology: Evolution of the disease. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2017;55(3):277-294 (In Russ.)
29. Bugatt S, Bogliolo L,Vitolo B, et al. Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis. Arthritis Res Ther. 2016;18:226. doi: 10.1186/s 13075- 016-1116-9
30. Wigerblad G, Bas DB, Fernades-Cerqueira C, et al. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis. 2016;75:730-8. doi: 10.1136/annrheumdis2015-208 094
31. Zhang ZJ, Cao DL, Zhang X, et al. Chemokine contribution to neuropathic pain: respective induction of CXCL1 and CXCR2 in spinal cord astrocytes and neurons. Pain. 2013;154:2185-97. doi: 10.1016/j.pain.2013.07.002
32. Titcombe PJ, Amara K, Barsness LO, et al. Citrullinatedself antigen-specific blood B cells carry cross reactive immunoglobulins with effector potential. Ann Rheum Dis. 2016;75(Suppl 1):A28-A29. doi: 10.1136/annrheumdis-2016-209124.68
33. Engel P, Gómez-Puerta J, Ramos-Casals M, et al. Therapeutic targeting of B cells for rheumatic autoimmune diseases. Pharmacol Rev. 2011;63:127-56. doi.org/10.1124/pr.109.002006
34. Lund F. Cytokine-producing B lymphocytes-key regulators of immunity. Curr Opin Immunol. 2008;20:332-8. doi.org/10.1016/j.coi.2008.03.003
35. Manjarrez-Orduño N, Quách T, Sanz I, et al. B cells and immunological tolerance. J Invest Dermatol. 2009;129:278-88.
36. Blom M, Wenink MH, Huijbens RJF, et al. Altered circulating cytokine pattern after administration of rituximab is correlated with response to therapy in rheumatoid arthritis. Arthritis Rheum. 2008;26(Suppl):764.
37. Fabre S, Gvisset C, Tatem L, et al. Protein biochip array technology to monitor rituximab in rheumatoid arthritis. Clin Exp Immunol. 2008;155:395-402. doi.org/10.1111/j.1365-2249.2008.03804.x
38. Szekanecz Z, Koch A. Successes and failures of chemokine-pathway targeting in rheumatoid arthritis. Nat Rev Rheumatol. 2016 Jan;12(1):5-13. doi: 10.1038/ nrrheum.2015.157. https://doi.org/10.1038/nrrheum.2015.157
39. Elyaman W, et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci. 2009;106:12885-90. doi.org/10.1073/pnas.0812530106
40. Nowak EC, et al. IL-9 as a mediator of Th17-driven inflammatory disease. J Exp Med. 2009;206:1653-60. doi.org/10.1084/jem.20090246
41. Bober LA, et al. Regulatory effects of interleukin-4 and interleukin-10 on human neutrophil function ex vivo and on neutrophil influx in a rat model of arthritis. Arthritis Rheum. 2000;43:2660-7. doi.org/10.1002/1529-0131(200012)43:12<26 60::aid-anr5>3.0.co;2-4
42. Smallie T, et al. IL-10 inhibits transcription elongation of the human TNF gene in primary macrophages. J Exp Med. 2010;207:2081-8. doi.org/10.1084/jem.20100414
43. vanRoon J, et al. Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. J Rheumatol. 2003;30:648-51.
44. Wong CK, et al. Effects of inflammatory cytokine IL-27 on the activation of fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Res Ther. 2010;12:R129. doi.org/10.1186/ar3067
45. Emery P, Fleishmann R, Filipowicz-Sosnowska A, et al. For the DANCER Study group. The Efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment. Results of a phase IIb randomized, double-blind, placebo-controlled dose-range trial. Arthritis Rheum. 2006;54:1390-400. doi.org/10.1002/art.21778
46. Emery P, Deodhar A, Rigby W, et al. Efficacy and Safety of different doses and retreatment of Rituximab: a randomized, placebo-controlled trial in patients who are biologically naïve with active rheumatoid arthritis and anadequate response to methotrexate (Study Evaluating Rituximab`s Efficacy in MTX inadequate responders (SERENA). Ann Rheum Dis. 2010;69:1629-35. doi.org/10.1136/ard.20 09.119933
47. Rubbert-Roth A, Tak P, Zebrini C, et al. Efficacy and safety of various repeat treatment dosing regimes in Rituximab in patients with active rheumatoid arthritis: results of a phase III randomized study (MIRROR) dosing regimens of rituximab in patients with active RA: results of a phase III randomized study (MIRROR). Rheumatology. 2010;49:1683-93. doi.org/10.1093/rheumatology/keq401
48. Roll P, Dorner T, Tony H-P. Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment. Arthritis Rheum. 2008;58:1566-75. doi.org/10.1002/art.23473
49. van Vollenhoven RF, Emery P, Bingham CO, et al. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol. 2010;37:558-67. doi.org/10.3899/jrheum.090856
50. Mariette X, Kivitz A, Isaacs J, et al. Effectiveness of Rituximab (RTX) + methotrexate (MTX) in patients (pts) with early active rheumatoid arthritis (RA) and disease charaxteristics associated with poor outcomes. Arthritis Rheum. 2009;60 (Suppl):631.
51. Tak P, Cohen S, Emery P, et al. Baseline autoantibody status (RF, ant-CCP) and clinical response following the first treatment course with rituximab. Arthritis Rheum. 2006;54(Suppl 9):368.
52. Tak P, Rigby W, Rubbert-Roth A. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70:39-46. doi.org/10.1136/ard.2010.137703
53. Khan A, Mahmud T, Hammond T, et al. Rituximab (RTX) is more effective in active sero-positive RA than sero-negative RA. Arthritis Rheum. 2010;62(Suppl 10):1830.
54. Isaacs JD, Olech E, Tak PP, et al. Autoantibody-positive rheumatoid arthritis patients have enchanced clinical response when compared with seronegative patients. Ann Rheum Dis. 2009;68(Suppl 3):442.
55. Silverman G, Schwartzman S, Townsend M, et al. Identification of biomarkers for enhanced benefit to Rituximab in rheumatoid arthritis: role for autoantibodies and inflammatory markers. Arthritis Rheum. 2009;60(Suppl.):628.
56. Sellam J, Hendel-Chavez H, Rouanet S, et al. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011;63:933-8. doi.org/ 10.1002/art.30233
57. Thurling R, Boumans M, Vos K, et al. Early changes in serum levels of cytokines and chemokines are predictive of the response to Rituximab treatment in rheumatoid arthritis. Arthritis Rheum. 2009;60(Suppl.):630.
2. Насонов Е.Л. Ритуксимаб. В кн.: Генно-инженерные биологические препараты в лечении ревматоидного артрита. Под ред. Е.Л. Насонова. М.: ИМА-ПРЕСС, 2013:200-221 [Nasonov EL. Rituximab. V kn.: Genno-inzhenernyebiologicheskiepreparaty v lecheniirevmatoidnogoartrita. Pod red. E.L. Nasonova Edited by EL. Nasonov. Moscow: IMA-PRESS, 2013:200-221 (In Russ.)].
3. Huscher D, Mittendorf T, von Hinuber U, et al. Evolution of cost structures in rheumatoid arthritis over the past decade. Ann Rheum Dis. 2015;74(4):738-45. doi.org/10.1136/annrheumdis-2013-204311
4. Насонов Е.Л. Биоаналоги в ревматологии. Научно-практическая ревматология. 2016;54(6):628-40 [Nasonov EL. Biosimilars in rheumatology. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(6):628-40 (In Russ.)]. doi: 10.14412/1995-4484-2016-628-640
5. Федеральный закон от 22 декабря 2014 г. №429-ФЗ «О внесении изменений в Федеральный закон "Об обращении лекарственных средств"». Принят Государственной Думой 9 декабря 2014 г. Одобрен Советом Федерации 17 декабря 2014 г. [Federal law of December 22, 2014 № 429-FZ «On Amendments to the Federal Law "On Circulation of Medicines"». Adopted by the State Duma on December 9, 2014 Approved by the Federation Council December 17, 2014 (In Russ.)].
6. Yoo DH, Suh CH, Shim SC, Jeka S, Molina FFC, Hrycaj P, Wiland P, Lee EY, Medina-Rodriguez FG, Shesternya P, Radominski S, Stanislav M, et all. Efficacy, Safety and Pharmacokinetics of Up to Two Courses of the Rituximab Biosimilar CT-P10 Versus Innovator Rituximab in Patients with Rheumatoid Arthritis: Results up to Week 72 of a Phase I Randomized Controlled Trial. Bio Drugs. 2017 Aug;31(4):357-67. doi: 10.1007/s40259-017-0232-7
7. Park W, Suh CH, Shim SC, et al. Efficacy and safety of switching from innovator rituximab to biosimilar CT-P10 compared with continued treatment with CT-P10: results of a 56-week open-label study in patients with rheumatoid arthritis. Bio Drugs. 2017 Jun 9; doi:10.1007/s40259-017-0233-6 [Epub ahead of print]
8. Yoo DH, Suh CH, Shim SC, Jeka S, Cons-Molina FF, Hrycaj P, Wiland P, Lee EY, Medina-Rodriguez FG, Shesternya P, Radominski S, Stanislav M, Kovalenko V, Sheen DH, Myasoutova L, Lim MJ, Choe JY, Lee SJ, Lee SY, Kwon TS, Park W. A multicentrerandomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Mar;76(3):566-70. doi: 10.1136/annrheumdis-2016-209540 Epub 2016 Sep 13.
9. Насонов Е.Л., Зонова Е.В., Иванова О.Н., Князева Л.А., Мазуров В.И. и др. Результаты сравнительного клинического исследования III фазы препаратов ритуксимаб (Ацеллбия и Мабтера) при ревматоидном артрите (исследование BIORA). Научно-практическая ревматология. 2016;54(5):510-9 [Nasonov EL, Zonova EV, Ivanova ON, et al. The results of a phase III comparative clinical trial of rituximab (Acellbia® and MabThera®) in rheumatoid arthritis (the BIORA study). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(5):510-9 (In Russ.)]. https://doi.org/10.14412/1995-4484-2016-510-519
10. Bredemeier M, de Oliveira FK, Rocha CM. Low-versus High-dose rituximab for rheumatoid arthritis: a systemic review and metaanalysis. Arthritis Care Res. 2014;66:228-35. https://doi.org/10.1002/acr.22116
11. Buch MH, Smolen JS, Betteridge N, et al. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70:909-20. doi: 10.1136/ard.2010.144998
12. Sacco JJ, Botten J, Macbeth F, Bagust A, Clark P. The Average Body Surface Area of Adult Cancer Patients in the UK: A Multicentre Retrospective Study. PLoS ONE. 2010;5(1):e8933. doi: 10.1371/journal.pone.0008933
13. Насонов Е.Л., Мазуров В.И., Зонова Е.В., Князева Л.А., Марусенко И.М. и др. Эффективность и безопасность биоаналога ритуксимаба (Ацеллбия®) при ревматоидном артрите в качестве «первого» генно-инженерного биологического препарата: результаты клинического исследования III фазы (ALTERRA). Научно-практическая ревматология. 2017;55(4):351-9 [Nasonov EL, Mazurov VI, Zonova EV, Knyazeva LA, Marusenko IM, et all. The efficacy and safety of rituximab biosimilar (Acellbia®) in rheumatoid arthritis as the first biological agent: results of phase iii (ALTERRA) clinical trial. Rheumatology Science and Practice. 2017;55(4):351-9 (In Russ.)]. https://doi.org/10.14412/1995-4484-2017-351-359
14. Cornec D, Avouac J, Youinou P, Saraux A. Critical analysis of rituximab-induced serological changes in connective tissue diseases. Autoimmun Rev. 2009;8:515-19. doi: 10.1016/j.autrev.2009.01.007
15. Grosjean C, de Chaisemartin L, Nicaise-Roland P, et al. Prospective cohort study of rituximab effects on rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis. Ann Rheum Dis. 2008;67(Suppl II):196.
16. Александрова Е.Н., Авдеева А.С., Лукина Г.В., Новиков А.А., Черкасова М.В., Попкова Т.В., Линева О.Г., Кузикянц К.Х., Насонов Е.Л. Клинико-иммунологические эффекты анти-В-клеточной терапии у больных ревматоидным артритом. Научно-практическая ревматология. 2012;50(1):14-21 [Aleksandrova EN, Avdeyeva AS, Lukina GV, Novikov AA, Cherkasova MV, Popkova TV, Lineva OG, Kuzikyants GK, Nasonov EL. The clinical and immunological effects of anti-b-cell therapy in patients with rheumatoid arthritis. Rheumatology Science and Practice. 2012;50(1):14-21 (In Russ.)]. https://doi.org/ 10.14412/1995-4484-2012-498
17. Cambridge G, Stohl W, Leandro MJ, et al. Circulating levels of Blymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationship with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum. 2006;54:723-32. doi: 10.1002/art.21650
18. Cohen S, Emery P, Greenwald M, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Results of multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54:2793-806. https://doi.org/10.1002/art. 22025
19. Higashida J, Wun T, Schmidt S. Safety and Efficacy of Rituximab in Patients with Rheumatoid Arthritis Refractory to Disease Modifying Antirheumatic Drugs and Anti-Tumor Necrosis Factor-a Treatment. Rheumatology. 2005;32:2109-15.
20. Tsiakalos A, Avgoustidis N, Moutsopoulos H. Rituximab therapy in Greek patients with rheumatoid arthritis. Biologics: Targets & Therapy. 2008;2:911-6. https://doi. org/10.2147/BTT.S3939
21. Bokarewa M, Lindholm C, Zendjanchi K, et al. Efficacy of Anti-CD20 treatment in patients with rheumatoid arthritis resistant to a combination of methotrexate/anti-TNF therapy. Scand J Immunol. 2007;66:467-83. https://doi.org/10.1111/j.1365-3083.2007.01995.x
22. Toubi E, Kesser A, Slobodin G, et al. Macrophage function changes following rituximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66: 818-20. https://doi.org/10.1136/ard.2006.062505
23. Vizioli C, Viana V, Ribeiro A. Auto-antibody titers for monitoring rituximab therapy in rheumatoid arthritis. Ann Rheum Dis. 2012;71(Suppl 3):667.
24. Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med. 2013;5:178ra 40. doi: 10.1126/scitranslmed.3005580
25. Aletaha D, Blüml S. Therapeutic implications of autoantibodies in rheumatoid arthritis. RMD Open. 2016;(2):e000009. doi: 10.1136/rmdopen-2014-000009
26. Harre U, Georgess D, Bang H, et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest. 2012;122:1791-802. doi: 10.1172/JCI60975
27. Harre U, Lang SC, Pfeifle R, et al. Glycosylation of immunoglobulin G determines osteoclast differentiation and bone lose. Nat Communocation. 2015. doi: 10.1038/ ncomms7651
28. Насонов Е.Л. Проблемы иммунопатологии ревматоидного артрита: эволюция болезни. Научно-практическая ревматология. 2017;55(3):277-94 [Nasonov EL. Problems of rheumatoid arthritis immunopathology: Evolution of the disease. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2017;55(3):277-294 (In Russ.)]
29. Bugatt S, Bogliolo L,Vitolo B, et al. Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis. Arthritis Res Ther. 2016;18:226. doi: 10.1186/s 13075- 016-1116-9
30. Wigerblad G, Bas DB, Fernades-Cerqueira C, et al. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis. 2016;75:730-8. doi: 10.1136/annrheumdis2015-208 094
31. Zhang ZJ, Cao DL, Zhang X, et al. Chemokine contribution to neuropathic pain: respective induction of CXCL1 and CXCR2 in spinal cord astrocytes and neurons. Pain. 2013;154:2185-97. doi: 10.1016/j.pain.2013.07.002
32. Titcombe PJ, Amara K, Barsness LO, et al. Citrullinatedself antigen-specific blood B cells carry cross reactive immunoglobulins with effector potential. Ann Rheum Dis. 2016;75(Suppl 1):A28-A29. doi: 10.1136/annrheumdis-2016-209124.68
33. Engel P, Gómez-Puerta J, Ramos-Casals M, et al. Therapeutic targeting of B cells for rheumatic autoimmune diseases. Pharmacol Rev. 2011;63:127-56. doi.org/10.1124/pr.109.002006
34. Lund F. Cytokine-producing B lymphocytes-key regulators of immunity. Curr Opin Immunol. 2008;20:332-8. doi.org/10.1016/j.coi.2008.03.003
35. Manjarrez-Orduño N, Quách T, Sanz I, et al. B cells and immunological tolerance. J Invest Dermatol. 2009;129:278-88.
36. Blom M, Wenink MH, Huijbens RJF, et al. Altered circulating cytokine pattern after administration of rituximab is correlated with response to therapy in rheumatoid arthritis. Arthritis Rheum. 2008;26(Suppl):764.
37. Fabre S, Gvisset C, Tatem L, et al. Protein biochip array technology to monitor rituximab in rheumatoid arthritis. Clin Exp Immunol. 2008;155:395-402. doi.org/10.1111/j.1365-2249.2008.03804.x
38. Szekanecz Z, Koch A. Successes and failures of chemokine-pathway targeting in rheumatoid arthritis. Nat Rev Rheumatol. 2016 Jan;12(1):5-13. doi: 10.1038/ nrrheum.2015.157. https://doi.org/10.1038/nrrheum.2015.157
39. Elyaman W, et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci. 2009;106:12885-90. doi.org/10.1073/pnas.0812530106
40. Nowak EC, et al. IL-9 as a mediator of Th17-driven inflammatory disease. J Exp Med. 2009;206:1653-60. doi.org/10.1084/jem.20090246
41. Bober LA, et al. Regulatory effects of interleukin-4 and interleukin-10 on human neutrophil function ex vivo and on neutrophil influx in a rat model of arthritis. Arthritis Rheum. 2000;43:2660-7. doi.org/10.1002/1529-0131(200012)43:12<26 60::aid-anr5>3.0.co;2-4
42. Smallie T, et al. IL-10 inhibits transcription elongation of the human TNF gene in primary macrophages. J Exp Med. 2010;207:2081-8. doi.org/10.1084/jem.20100414
43. vanRoon J, et al. Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. J Rheumatol. 2003;30:648-51.
44. Wong CK, et al. Effects of inflammatory cytokine IL-27 on the activation of fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Res Ther. 2010;12:R129. doi.org/10.1186/ar3067
45. Emery P, Fleishmann R, Filipowicz-Sosnowska A, et al. For the DANCER Study group. The Efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment. Results of a phase IIb randomized, double-blind, placebo-controlled dose-range trial. Arthritis Rheum. 2006;54:1390-400. doi.org/10.1002/art.21778
46. Emery P, Deodhar A, Rigby W, et al. Efficacy and Safety of different doses and retreatment of Rituximab: a randomized, placebo-controlled trial in patients who are biologically naïve with active rheumatoid arthritis and anadequate response to methotrexate (Study Evaluating Rituximab`s Efficacy in MTX inadequate responders (SERENA). Ann Rheum Dis. 2010;69:1629-35. doi.org/10.1136/ard.20 09.119933
47. Rubbert-Roth A, Tak P, Zebrini C, et al. Efficacy and safety of various repeat treatment dosing regimes in Rituximab in patients with active rheumatoid arthritis: results of a phase III randomized study (MIRROR) dosing regimens of rituximab in patients with active RA: results of a phase III randomized study (MIRROR). Rheumatology. 2010;49:1683-93. doi.org/10.1093/rheumatology/keq401
48. Roll P, Dorner T, Tony H-P. Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment. Arthritis Rheum. 2008;58:1566-75. doi.org/10.1002/art.23473
49. van Vollenhoven RF, Emery P, Bingham CO, et al. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol. 2010;37:558-67. doi.org/10.3899/jrheum.090856
50. Mariette X, Kivitz A, Isaacs J, et al. Effectiveness of Rituximab (RTX) + methotrexate (MTX) in patients (pts) with early active rheumatoid arthritis (RA) and disease charaxteristics associated with poor outcomes. Arthritis Rheum. 2009;60 (Suppl):631.
51. Tak P, Cohen S, Emery P, et al. Baseline autoantibody status (RF, ant-CCP) and clinical response following the first treatment course with rituximab. Arthritis Rheum. 2006;54(Suppl 9):368.
52. Tak P, Rigby W, Rubbert-Roth A. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70:39-46. doi.org/10.1136/ard.2010.137703
53. Khan A, Mahmud T, Hammond T, et al. Rituximab (RTX) is more effective in active sero-positive RA than sero-negative RA. Arthritis Rheum. 2010;62(Suppl 10):1830.
54. Isaacs JD, Olech E, Tak PP, et al. Autoantibody-positive rheumatoid arthritis patients have enchanced clinical response when compared with seronegative patients. Ann Rheum Dis. 2009;68(Suppl 3):442.
55. Silverman G, Schwartzman S, Townsend M, et al. Identification of biomarkers for enhanced benefit to Rituximab in rheumatoid arthritis: role for autoantibodies and inflammatory markers. Arthritis Rheum. 2009;60(Suppl.):628.
56. Sellam J, Hendel-Chavez H, Rouanet S, et al. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011;63:933-8. doi.org/ 10.1002/art.30233
57. Thurling R, Boumans M, Vos K, et al. Early changes in serum levels of cytokines and chemokines are predictive of the response to Rituximab treatment in rheumatoid arthritis. Arthritis Rheum. 2009;60(Suppl.):630.
________________________________________________
2. Nasonov EL. Rituximab. V kn.: Genno-inzhenernyebiologicheskiepreparaty v lecheniirevmatoidnogoartrita. Pod red. E.L. Nasonova Edited by EL. Nasonov. Moscow: IMA-PRESS, 2013:200-221 (In Russ.).
3. Huscher D, Mittendorf T, von Hinuber U, et al. Evolution of cost structures in rheumatoid arthritis over the past decade. Ann Rheum Dis. 2015;74(4):738-45. doi.org/10.1136/annrheumdis-2013-204311
4. Nasonov EL. Biosimilars in rheumatology. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(6):628-40 (In Russ.). doi: 10.14412/1995-4484-2016-628-640
5. Federal law of December 22, 2014 № 429-FZ «On Amendments to the Federal Law "On Circulation of Medicines"». Adopted by the State Duma on December 9, 2014 Approved by the Federation Council December 17, 2014 (In Russ.).
6. Yoo DH, Suh CH, Shim SC, Jeka S, Molina FFC, Hrycaj P, Wiland P, Lee EY, Medina-Rodriguez FG, Shesternya P, Radominski S, Stanislav M, et all. Efficacy, Safety and Pharmacokinetics of Up to Two Courses of the Rituximab Biosimilar CT-P10 Versus Innovator Rituximab in Patients with Rheumatoid Arthritis: Results up to Week 72 of a Phase I Randomized Controlled Trial. Bio Drugs. 2017 Aug;31(4):357-67. doi: 10.1007/s40259-017-0232-7
7. Park W, Suh CH, Shim SC, et al. Efficacy and safety of switching from innovator rituximab to biosimilar CT-P10 compared with continued treatment with CT-P10: results of a 56-week open-label study in patients with rheumatoid arthritis. Bio Drugs. 2017 Jun 9; doi:10.1007/s40259-017-0233-6 [Epub ahead of print]
8. Yoo DH, Suh CH, Shim SC, Jeka S, Cons-Molina FF, Hrycaj P, Wiland P, Lee EY, Medina-Rodriguez FG, Shesternya P, Radominski S, Stanislav M, Kovalenko V, Sheen DH, Myasoutova L, Lim MJ, Choe JY, Lee SJ, Lee SY, Kwon TS, Park W. A multicentrerandomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Mar;76(3):566-70. doi: 10.1136/annrheumdis-2016-209540 Epub 2016 Sep 13.
9. Nasonov EL, Zonova EV, Ivanova ON, et al. The results of a phase III comparative clinical trial of rituximab (Acellbia® and MabThera®) in rheumatoid arthritis (the BIORA study). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(5):510-9 (In Russ.). https://doi.org/10.14412/1995-4484-2016-510-519
10. Bredemeier M, de Oliveira FK, Rocha CM. Low-versus High-dose rituximab for rheumatoid arthritis: a systemic review and metaanalysis. Arthritis Care Res. 2014;66:228-35. https://doi.org/10.1002/acr.22116
11. Buch MH, Smolen JS, Betteridge N, et al. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70:909-20. doi: 10.1136/ard.2010.144998
12. Sacco JJ, Botten J, Macbeth F, Bagust A, Clark P. The Average Body Surface Area of Adult Cancer Patients in the UK: A Multicentre Retrospective Study. PLoS ONE. 2010;5(1):e8933. doi: 10.1371/journal.pone.0008933
13. Nasonov EL, Mazurov VI, Zonova EV, Knyazeva LA, Marusenko IM, et all. The efficacy and safety of rituximab biosimilar (Acellbia®) in rheumatoid arthritis as the first biological agent: results of phase iii (ALTERRA) clinical trial. Rheumatology Science and Practice. 2017;55(4):351-9 (In Russ.). https://doi.org/10.14412/1995-4484-2017-351-359
14. Cornec D, Avouac J, Youinou P, Saraux A. Critical analysis of rituximab-induced serological changes in connective tissue diseases. Autoimmun Rev. 2009;8:515-19. doi: 10.1016/j.autrev.2009.01.007
15. Grosjean C, de Chaisemartin L, Nicaise-Roland P, et al. Prospective cohort study of rituximab effects on rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis. Ann Rheum Dis. 2008;67(Suppl II):196.
16. Aleksandrova EN, Avdeyeva AS, Lukina GV, Novikov AA, Cherkasova MV, Popkova TV, Lineva OG, Kuzikyants GK, Nasonov EL. The clinical and immunological effects of anti-b-cell therapy in patients with rheumatoid arthritis. Rheumatology Science and Practice. 2012;50(1):14-21 (In Russ.) https://doi.org/ 10.14412/1995-4484-2012-498
17. Cambridge G, Stohl W, Leandro MJ, et al. Circulating levels of Blymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationship with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum. 2006;54:723-32. doi: 10.1002/art.21650
18. Cohen S, Emery P, Greenwald M, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Results of multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54:2793-806. https://doi.org/10.1002/art. 22025
19. Higashida J, Wun T, Schmidt S. Safety and Efficacy of Rituximab in Patients with Rheumatoid Arthritis Refractory to Disease Modifying Antirheumatic Drugs and Anti-Tumor Necrosis Factor-a Treatment. Rheumatology. 2005;32:2109-15.
20. Tsiakalos A, Avgoustidis N, Moutsopoulos H. Rituximab therapy in Greek patients with rheumatoid arthritis. Biologics: Targets & Therapy. 2008;2:911-6. https://doi. org/10.2147/BTT.S3939
21. Bokarewa M, Lindholm C, Zendjanchi K, et al. Efficacy of Anti-CD20 treatment in patients with rheumatoid arthritis resistant to a combination of methotrexate/anti-TNF therapy. Scand J Immunol. 2007;66:467-83. https://doi.org/10.1111/j.1365-3083.2007.01995.x
22. Toubi E, Kesser A, Slobodin G, et al. Macrophage function changes following rituximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66: 818-20. https://doi.org/10.1136/ard.2006.062505
23. Vizioli C, Viana V, Ribeiro A. Auto-antibody titers for monitoring rituximab therapy in rheumatoid arthritis. Ann Rheum Dis. 2012;71(Suppl 3):667.
24. Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med. 2013;5:178ra 40. doi: 10.1126/scitranslmed.3005580
25. Aletaha D, Blüml S. Therapeutic implications of autoantibodies in rheumatoid arthritis. RMD Open. 2016;(2):e000009. doi: 10.1136/rmdopen-2014-000009
26. Harre U, Georgess D, Bang H, et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest. 2012;122:1791-802. doi: 10.1172/JCI60975
27. Harre U, Lang SC, Pfeifle R, et al. Glycosylation of immunoglobulin G determines osteoclast differentiation and bone lose. Nat Communocation. 2015. doi: 10.1038/ ncomms7651
28. Nasonov EL. Problems of rheumatoid arthritis immunopathology: Evolution of the disease. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2017;55(3):277-294 (In Russ.)
29. Bugatt S, Bogliolo L,Vitolo B, et al. Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis. Arthritis Res Ther. 2016;18:226. doi: 10.1186/s 13075- 016-1116-9
30. Wigerblad G, Bas DB, Fernades-Cerqueira C, et al. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis. 2016;75:730-8. doi: 10.1136/annrheumdis2015-208 094
31. Zhang ZJ, Cao DL, Zhang X, et al. Chemokine contribution to neuropathic pain: respective induction of CXCL1 and CXCR2 in spinal cord astrocytes and neurons. Pain. 2013;154:2185-97. doi: 10.1016/j.pain.2013.07.002
32. Titcombe PJ, Amara K, Barsness LO, et al. Citrullinatedself antigen-specific blood B cells carry cross reactive immunoglobulins with effector potential. Ann Rheum Dis. 2016;75(Suppl 1):A28-A29. doi: 10.1136/annrheumdis-2016-209124.68
33. Engel P, Gómez-Puerta J, Ramos-Casals M, et al. Therapeutic targeting of B cells for rheumatic autoimmune diseases. Pharmacol Rev. 2011;63:127-56. doi.org/10.1124/pr.109.002006
34. Lund F. Cytokine-producing B lymphocytes-key regulators of immunity. Curr Opin Immunol. 2008;20:332-8. doi.org/10.1016/j.coi.2008.03.003
35. Manjarrez-Orduño N, Quách T, Sanz I, et al. B cells and immunological tolerance. J Invest Dermatol. 2009;129:278-88.
36. Blom M, Wenink MH, Huijbens RJF, et al. Altered circulating cytokine pattern after administration of rituximab is correlated with response to therapy in rheumatoid arthritis. Arthritis Rheum. 2008;26(Suppl):764.
37. Fabre S, Gvisset C, Tatem L, et al. Protein biochip array technology to monitor rituximab in rheumatoid arthritis. Clin Exp Immunol. 2008;155:395-402. doi.org/10.1111/j.1365-2249.2008.03804.x
38. Szekanecz Z, Koch A. Successes and failures of chemokine-pathway targeting in rheumatoid arthritis. Nat Rev Rheumatol. 2016 Jan;12(1):5-13. doi: 10.1038/ nrrheum.2015.157. https://doi.org/10.1038/nrrheum.2015.157
39. Elyaman W, et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci. 2009;106:12885-90. doi.org/10.1073/pnas.0812530106
40. Nowak EC, et al. IL-9 as a mediator of Th17-driven inflammatory disease. J Exp Med. 2009;206:1653-60. doi.org/10.1084/jem.20090246
41. Bober LA, et al. Regulatory effects of interleukin-4 and interleukin-10 on human neutrophil function ex vivo and on neutrophil influx in a rat model of arthritis. Arthritis Rheum. 2000;43:2660-7. doi.org/10.1002/1529-0131(200012)43:12<26 60::aid-anr5>3.0.co;2-4
42. Smallie T, et al. IL-10 inhibits transcription elongation of the human TNF gene in primary macrophages. J Exp Med. 2010;207:2081-8. doi.org/10.1084/jem.20100414
43. vanRoon J, et al. Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. J Rheumatol. 2003;30:648-51.
44. Wong CK, et al. Effects of inflammatory cytokine IL-27 on the activation of fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Res Ther. 2010;12:R129. doi.org/10.1186/ar3067
45. Emery P, Fleishmann R, Filipowicz-Sosnowska A, et al. For the DANCER Study group. The Efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment. Results of a phase IIb randomized, double-blind, placebo-controlled dose-range trial. Arthritis Rheum. 2006;54:1390-400. doi.org/10.1002/art.21778
46. Emery P, Deodhar A, Rigby W, et al. Efficacy and Safety of different doses and retreatment of Rituximab: a randomized, placebo-controlled trial in patients who are biologically naïve with active rheumatoid arthritis and anadequate response to methotrexate (Study Evaluating Rituximab`s Efficacy in MTX inadequate responders (SERENA). Ann Rheum Dis. 2010;69:1629-35. doi.org/10.1136/ard.20 09.119933
47. Rubbert-Roth A, Tak P, Zebrini C, et al. Efficacy and safety of various repeat treatment dosing regimes in Rituximab in patients with active rheumatoid arthritis: results of a phase III randomized study (MIRROR) dosing regimens of rituximab in patients with active RA: results of a phase III randomized study (MIRROR). Rheumatology. 2010;49:1683-93. doi.org/10.1093/rheumatology/keq401
48. Roll P, Dorner T, Tony H-P. Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment. Arthritis Rheum. 2008;58:1566-75. doi.org/10.1002/art.23473
49. van Vollenhoven RF, Emery P, Bingham CO, et al. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. J Rheumatol. 2010;37:558-67. doi.org/10.3899/jrheum.090856
50. Mariette X, Kivitz A, Isaacs J, et al. Effectiveness of Rituximab (RTX) + methotrexate (MTX) in patients (pts) with early active rheumatoid arthritis (RA) and disease charaxteristics associated with poor outcomes. Arthritis Rheum. 2009;60 (Suppl):631.
51. Tak P, Cohen S, Emery P, et al. Baseline autoantibody status (RF, ant-CCP) and clinical response following the first treatment course with rituximab. Arthritis Rheum. 2006;54(Suppl 9):368.
52. Tak P, Rigby W, Rubbert-Roth A. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70:39-46. doi.org/10.1136/ard.2010.137703
53. Khan A, Mahmud T, Hammond T, et al. Rituximab (RTX) is more effective in active sero-positive RA than sero-negative RA. Arthritis Rheum. 2010;62(Suppl 10):1830.
54. Isaacs JD, Olech E, Tak PP, et al. Autoantibody-positive rheumatoid arthritis patients have enchanced clinical response when compared with seronegative patients. Ann Rheum Dis. 2009;68(Suppl 3):442.
55. Silverman G, Schwartzman S, Townsend M, et al. Identification of biomarkers for enhanced benefit to Rituximab in rheumatoid arthritis: role for autoantibodies and inflammatory markers. Arthritis Rheum. 2009;60(Suppl.):628.
56. Sellam J, Hendel-Chavez H, Rouanet S, et al. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011;63:933-8. doi.org/ 10.1002/art.30233
57. Thurling R, Boumans M, Vos K, et al. Early changes in serum levels of cytokines and chemokines are predictive of the response to Rituximab treatment in rheumatoid arthritis. Arthritis Rheum. 2009;60(Suppl.):630.
Авторы
А.С. Авдеева 1, М.В. Черкасова 1, Д.А. Кусевич 2, В.В. Рыбакова 2, А.С. Артюхов 3, Э.Б. Дашинимаев 3, Н.В. Чичасова 1,2, Е.Л. Насонов 1,2
1 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
2 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова»» Минздрава России (Сеченовский Университет), Москва, Россия;
3 Российский национальный исследовательский медицинский университет им. Н.И. Пирогова, Научно-исследовательский институт трансляционной медицины, отдел регенеративной медицины; институт биологии развития (ИБР) РАН, лаборатория проблем клеточной пролиферации, Москва, Россия
1 V.A. Nasonova Scientific and Research Institute of Rheumatology, Moscow, Russia;
2 I.M. Sechenov First Moscow State Medical University of Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia;
3 Department of Regenerative Medicine; Institute of Developmental Biology, Russian Academy of Sciences, Laboratory of Cell Proliferation, Pirogov Russian National Research Medical University, Moscow, Russia
1 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
2 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова»» Минздрава России (Сеченовский Университет), Москва, Россия;
3 Российский национальный исследовательский медицинский университет им. Н.И. Пирогова, Научно-исследовательский институт трансляционной медицины, отдел регенеративной медицины; институт биологии развития (ИБР) РАН, лаборатория проблем клеточной пролиферации, Москва, Россия
________________________________________________
1 V.A. Nasonova Scientific and Research Institute of Rheumatology, Moscow, Russia;
2 I.M. Sechenov First Moscow State Medical University of Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia;
3 Department of Regenerative Medicine; Institute of Developmental Biology, Russian Academy of Sciences, Laboratory of Cell Proliferation, Pirogov Russian National Research Medical University, Moscow, Russia
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