Preview

Научно-практическая ревматология

Расширенный поиск

Биоаналоги в ревматологии

https://doi.org/10.14412/1995-4484-2016-628-640

Аннотация

Одно из наиболее ярких достижений фармакотерапии ревматоидного артрита (РА) и других иммуновоспалительных заболеваний (ИВЗ) человека конца ХХ в. связано с разработкой принципиально новой группы лекарственных средств, которые получили название «генно-инженерные биологические препараты» (ГИБП). Однако внедрение инновационных ГИБП в клиническую практику не только позволило повысить эффективность терапии и улучшить прогноз у пациентов, страдающих наиболее тяжелыми формами ИВЗ, но и привело к кардинальному удорожанию лечения. Прогресс в разработке биоаналогов (biosimilars) ГИБП связан со многими факторами, в том числе c окончанием срока действия патентов на многие оригинальные ГИБП, такие как инфликсимаб, адалимумаб, этанерцепт, ритуксимаб. За последние 5 лет было разработано и продолжает разрабатываться большое число биоаналогов ГИБП. Европейское медицинское агентство (European Medicines Agency – EMA), Всемирная организация здравоохранения (ВОЗ) и Управление по санитарному надзору за качеством пищевых продуктов и медикаментов США (Food and Drug Administration – FDA) разработали регуляторные основы, общие требования к производству и характеристике биоаналогов. В Федеральном законе от 22 декабря 2014 г. № 429-ФЗ «О внесении изменений в Федеральный закон "Об обращении лекарственных средств"» биоаналоговый (биоподобный) лекарственный препарат (биоаналог) определяется как биологический лекарственный препарат, схожий по параметрам качества, эффективности и безопасности с референтным биологическим лекарственным препаратом в такой же лекарственной форме и имеющий идентичный способ введения. В обзоре представлены современные данные, касающиеся требований к биоаналогам ГИБП, применяемым для лечения ИВЗ, их взаимозаменяемости и перспектив применения в клинической практике. Особое внимание уделяется биоаналогу химерных моноклональных антител к фактору некроза опухоли α инфликсимаба – препарату Фламмэгиc (Flammegis; Egis Pharmaceuticals, Венгрия), который зарегистрирован в России для лечения РА, анкилозирующего спондилита и других ИВЗ, а также биоаналогу химерных моноклональных антител к В-лимфоцитам ритуксимаба – препарату Ацеллбия, III фаза клинических испытаний которого завешается. Сформулированы предварительные положения и рекомендации Общероссийской общественной организации «Ассоциация ревматологов России», касающиеся места биоаналогов в ревматологии.

Об авторе

Е. Л. Насонов
ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой» ФГБОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России
Россия

115522 Москва, Каширское шоссе, 34А;

119991 Москва, ул. Трубецкая, 8, стр. 2 кафедра ревматологии Института профессионального образования, Москва, Россия



Список литературы

1. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388:2023-38. doi: 10.1016/S0140-6736(16)30173-8

2. Насонов ЕЛ, редактор. Генно-инженерные биологические препараты в лечении ревматоидного артрита. Москва: ИМА-ПРЕСС; 2013 [Nasonov EL, editor. Genno- inzhenernye biologicheskie preparaty v lechenii revmatoidnogo artrita [Genetically engineered biological agents in the treatment of rheumatoid arthritis]. Moscow: IMA- PRESS; 2013].

3. Siebert S, Tsoukas A, Robertson J, McInnes I. Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases. Pharmacol Rev. 2015;67:280-309. doi: 10.1124/pr.114.009639

4. Zhang Q, Vignali DA. Co-stimulatory and co-inhibitory Pathways in Autoimmunity. Immunity. 2016 May 17;44(5):1034-51. doi: 10.1016/j.immuni.2016.04.017

5. Huscher D, Mittendorf T, von Hinuber U, et al. Evolution of cost structures in rheumatoid arthritis over the past decade. Ann Rheum Dis. 2015;74:738-45. doi: 10.1136/annrheumdis-2013-204311

6. Putrik P, Ramiro S, Kvien TK, et al. Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis. 2014;73:198-206. doi: 10.1136/annrheumdis-2012-202603

7. Putrik P, Ramiro S, Kvien TK, et al. Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth? Ann Rheum Dis. 2014;73:2010-21. doi: 10.1136/annrheumdis-2013- 203819

8. Dö rner T, Strand V, Castaneda-Hernandez G, et al. The role of biosimilars in the treatment of rheumatic diseases. Ann Rheum Dis. 2013;72:322-8. doi: 10.1136/annrheumdis-2012-202715

9. Scheinberg MA, Kay J. The advent of biosimilar therapies in rheumatology – «O Brave New World». Nat Rev Rheum. 2012;8:430-6. doi: 10.1038/nrrheum.2012.84

10. Goel N, Chance K. Biosimilars in rheumatology: understanding the rigor of their development. Rheumatology (Oxford). 2016 May 30. pii: kew206 [Epub ahead of print].

11. Dö rner T, Strand V, Cornes P, et al. The changing landscape of biosimilars in rheumatology. Ann Rheum Dis. 2016;75:974-82. doi: 10.1136/annrheumdis-2016-20

12. Haustein R, Millas C, Hö er A, Hä ussler B. Saving money in the European healthcare systems with biosimilars. Generics Biosimilars Initiat J. 2012;1:120-6. doi: 10.5639/gabij.2012.0103-4.036

13. Rand corporation. The cost savings potential of biosimilar drugs in the United States(2014). Available from: http://www.rand.org/content/dam/rand/pubs/perspectives/PE100/PE127/RAND_PE127.pdf

14. Dolinar RO, Reilly MS. Biosimilars naming, label transparency and authority of choice – survey findings among European physicians. GaBi J. 2014;3:58-62. doi: 10.5639/gabij.2014.0302.018

15. Guideline on similar biological medical products. European Medical Agency. VHMP/437/04.London, 30 October 2005. Available from: http:/www.emea.eu.int

16. WHO Expert Committee on Biological Standardization. Guidelines on evaluation of similar biotherapeutic products (SBPs), annex 2. World Health Organ Tech Rep Ser. 2013;977:53-89.

17. U.S. Food and Drug Administration. Biosimilars. Available from: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/Therapeutic BiologicApplications/Biosimilars/default.htm. Accessed 13 January 2016.

18. European Medicines Agency. Biosimilar Medicines. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/document_listing/document_listing_000318.jsp. Accessed 13 January 2016.

19. 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].

20. U.S. Food and Drug Administration. Guidance for industry. Quality considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. 2015. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291134.pdf. Accessed 14 January 2016.

21. European Medicines Agency. Guideline on similar biological medicinal products. 2014. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/10/WC500176768.pdf. Accessed 2 February 2015.

22. European Medicines Agency. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. 2014. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/01/WC500180219.pdf. Accessed 7 January 2016.

23. U.S. Food and Drug Administration. Guidance for industry. Scientific considerations in demonstrating biosimilarity to a reference product. 2015. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf. Accessed 2 February 2015.

24. Schneider CK. Biosimilars in rheumatology: the wind of change. Ann Rheum Dis. 2013;72:315-8. doi: 10.1136/annrheumdis-2012-202941

25. U.S. Food and Drug Administration. Guidance for industry. Q5e comparability of biotechnological/biological products subject to changes in their manufacturing process. 2005. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf. Accessed 20January 2016.

26. Dorner T, Kay J. Biosimilars in rheumatology: current perspectives and lessons learnt. Nat Rev Rheumatol. 2015;11:713-24. doi: 10.1038/nrrheum.2015.110

27. U.S. Food and Drug Administration. Guidance for industry. Biosimilars: questions and answers regarding implementation of the Biologics Price Competition and Innovation Act of 2009. 2015. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM444661.pdf. Accessed 13 January 2016.

28. Braun J, Kudrin A. Switching to biosimilar infliximab (CT-P13): Evidence of clinical safety, effectiveness and impact on public health. Biologicals. 2016;44:257-66. doi: 10.1016/j.biologicals.2016.03.006

29. ACR Committee on Rheumatologic Care. ACR Position Statements – Biosimilars. American College of Rheumatology [online], (2015).

30. EULAR. Biosimilars: what do patients need to consider? The European League Against Rheumatism [online], (2015).

31. European Commission. Commission implementing directive 2012/52/EU of 20 December 2012 laying down measures to facilitate the recognition of medical prescriptions issued in another Member State [online], (2012).

32. US Department of Health & Human Services. Biosimilars: questions and answers regarding implementation of the Biologics Price Competition and Innovation Act of 2009. US Food and Drug Administration [online], (2012).

33. Danese S, Gomollon F. ECCO position statement: The use of biosimilar medicines in the treatment of inflammatory bowel disease (IBD). J Crohns Colitis. 2013;7:586-9. doi: 10.1016/j.crohns.2013.03.011

34. Danese S, Florino G, Michetti P. Viewpoint: Knowledge and viewpoints on biosimilar monoclonal antibodies among members of the European Crohn's and Colitis Organization. J Crohns Colitis. 2014;8:1548-50. doi: 10.1016/j.crohns.2014.06.007

35. Fiorino G, Danese S. The biosimilar road in inflammatory bowel disease: the right way? Best Pract Res Clin Gastroenterol. 2014;28:465-71. doi: 10.1016/j.bpg.2014.04.006

36. Hlavaty T, Letkovsky J. Biosimilars in the therapy of inflammatory bowel diseases. Eur J Gastroenterol Hepatol. 2014;26:581-7. doi: 10.1097/meg.0000000000000098

37. Fiorino G, Girolomoni G, Lapadula G, et al.; SIR, SIDeMaST, and IG-IBD. The use of biosimilars in immune-mediated disease: a joint Italian Society of Rheumatology (SIR), Italian Society of Dermatology (SIDeMaST), and Italian Group of Inflammatory Bowel Disease (IG-IBD) position paper. Autoimmun Rev. 2014;13:751-5. doi: 10.1016/j.autrev.2014.02.004

38. Schreiber S, Luger T, Mittendorf T, et al. Evolution of biologicals in inflammation medicine – biosimilars in gastroenterology, rheumatology and dermatology [In Germ.]. Dtsch Med. Wochenschr. 2014;139:2399-404. doi: 10.1055/s-0034-1387371

39. European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). Assessment report: Remsima (infliximab). 27 June 2013. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002576/WC500151486.pdf. Accessed 2 October 2014.

40. Isaacs JD, Cutolo M, Keystone EC, et al. Biosimilars in immune-mediated inflammatory diseases: initial lessons from the first approved biosimilar anti-tumour necrosis factor monoclonal antibody. J Intern Med. 2016;279:41-59. doi: 10.1111/joim.12432

41. Chingcuanco F, Segal JB, Kim SC, Alexander GC. Bioequivalence of biosimilar tumor necrosis factor-α inhibitors compared with their reference biologics: A systematic review. Ann Intern Med. 2016;165(8):565-74. doi: 10.7326/M16-0428

42. European Medicines Agency. Remsima (infliximab). Summary of Product Characteristics. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002576/WC500150871.pdf. Accessed 22 October 2014.

43. European Medicines Agency. Remicade (infliximab). Summary of Product Characteristics. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000240/WC500050888.pdf. Accessed 22 October 2014.

44. Park W, Hrycaj P, Jeka S, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis. 2013;72:1605-12. doi: 10.1136/annrheumdis-2012-203091

45. Yoo DH, Hrycaj P, Miranda P, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72:1613-20. doi: 10.1136/annrheumdis-2012-203090

46. Park W, Yoo DH, Jaworski J, et al. Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallelgroup PLANETAS study. Arthritis Res Ther. 2016 Jan 20;18:25. doi: 10.1186/s13075- 016-0930-4

47. Park W, Yoo DH, Miranda P, et al. Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102- week data from the PLANETAS extension study. Ann Rheum Dis. 2016 Apr 26. doi: 10.1136/annrheumdis-2015-208783

48. Yoo DH, Racewicz A, Brzezicki J, et al. A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study. Arthritis Res Ther. 2016 Apr 2;18:82. doi: 10.1186/s13075-016-0981-6

49. Yoo DH, Prodanovic N, Jaworski J, et al. Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study. Ann Rheum Dis. 2016 Apr 29. doi: 10.1136/annrheumdis-2015-208786

50. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52:3381-90. doi: 10.1002/art.21405

51. Baji P, Pentek M, Czirjak L, et al. Efficacy and safety of infliximab-biosimilar compared to other biological drugs in rheumatoid arthritis: a mixed treatment comparison. Eur J Health Econ. 2014;15 Suppl 1:S53-64. doi: 10.1007/s10198-014-0594-4

52. Gulacsi L, Brodszky V, Baji P, et al. Biosimilars for the management of rheumatoid arthritis: economic considerations. Expert Rev Clin Immunol. 2015;11 Suppl 1:43-52. doi: 10.1586/1744666X.2015.1090313

53. Kim J, Hong J, Kudrin A. 5 year budget impact analysis of biosimilar infliximab for the treatment of rheumatoid arthritis in UK, Italy, France and Germany. Presented at ACR/ARHP Annual Meeting, Boston, MA, USA; 14-19 November 2014. Abstract No 1166.

54. Jha A, Upton A, Dunlop WCN, et al. The budget impact of biosimilar infliximab (Remsima®) for the treatment of autoimmune diseases in five European countries. Adv Ther. 2015;32:742- 56. doi: 10.1007/s12325-015-0233-1

55. Lucioni C, Mazzi S, Caporali R. Analisi di budget impact del biosimilare di infliximab: lo scenario italiano. Glob Reg Health Technol Assess. 2015;2:78-88.

56. McCarthy G, Guy H. Introduction of an infliximab biosimilar (CT-P13): A five-year budget impact analysis for the treatment of rheumatoid arthritis in Ireland. Value Health. 2013;16(7):A558. doi: 10.1016/j.jval.2013.08.1465

57. Brodszky V, Baji P, Balogh O, Pentek M. Budget impact analysis of biosimilar infliximab (CT-P13) for the treatment of rheumatoid arthritis in six Central and Eastern European countries. Eur J Health Econ. 2014 May;15 Suppl 1:S65-71. doi: 10.1007/s10198-014-0595-3

58. Капланов КД, Зарицкий АЮ, Алексеев СМ и др. Начало эры применения биоаналогов моноклональных антител в онкологии: современные международные рекомендации и результаты исследования первого российского биоаналога ритуксимаба у больных В-клеточной неходжкинской лимфомой. Современная онкология. 2014;16:38-44 [Kaplanov KD, Zaritskey AY, Alekseev SM, et al. The beginning of the new era of monoclonal antibodies biosimilars use in oncology: current international guidelines and the results of clinical trial of the first russian rituximab biosimilar in patients with B-cell non-Hodgkin’s lymphoma. Sovremennaya Onkologiya = Journal of Modern Oncology. 2014;16(2):38-44 (In Russ.)].

59. Насонов ЕЛ, Зонова ЕВ, Иванова ОН и др. Результаты сравнительного клинического исследования III фазы препаратов ритуксимаба (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.)]. doi: 10.14412/1995-4484-2016-510-519

60. Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69:964-75. doi: 10.1136/ard.2009.126532

61. Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73:492-509. doi: 10.1136/annrheumdis-2013-204573

62. Насонов ЕЛ, Мазуров ВИ, Каратеев ДЕ и др. Проект рекомендаций по лечению ревматоидного артрита Общероссийской общественной организации «Ассоциация ревматологов России» – 2014 (часть 1). Научно-практическая ревматология. 2014;52(5):477-94 [Nasonov EL, Mazurov VI, Karateev DE, et al. Spondyloarthritis: Evolution of a concept. Project: recommendations on treatment of rheumatoid arthritis developed by All-Russian Public organization «Association of Rheumatologists of Russia» – 2014 (part 1). Nauchno- Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(5):477-94 (In Russ.)]. doi: 10.14412/1995-4484-2014-477-494

63. National Institute for Health and Care Excellence (UK). Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed [online] (2016).

64. Насонов ЕЛ, Каратеев ДЕ, Чичасова НВ. Рекомендации EULAR по лечению ревматоидного артрита – 2013: общая характеристика и дискуссионные проблемы. Научно- практическая ревматология. 2013;51(6):609-22 [Nasonov EL, Karateev DE, Chichasova NV. EULAR recommendations for the treatment of rheumatoid arthritis – 2013: general characteristics and disputable problems. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(6):609-22 (In Russ.)]. doi: 10.14412/1995-4484- 2013-609-22

65. Насонов ЕЛ, Каратеев ДЕ, Чичасова НВ. Новые рекомендации по лечению ревматоидного артрита (EULAR, 2013): место метотрексата. Научно-практическая ревматология 2014;52(1):8-26 [Nasonov EL, Karateev DE, Chichasova NV. New recommendations for the management of rheumatoid arthritis (EULAR, 2013): the role of methotrexate. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(1):8-26 (In Russ.)]. doi: 10.14412/1995-4484-2014-8-26

66. Hazlewood GS, Barnabe C, Tomilison G, et al. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systemic review and network meta-analysis. BMJ. 2016;353:i1777. doi: 10.1136/bmj.i1777

67. Espinosa F, Fabre S, Pers Y-M. Remission-induction therapies for early rheumatoid arthritis: evidence to date and clinical implications. Ther Adv Musculoskelet Dis. 2016;8:107- 18. doi: 10.1177/175920X16654476

68. Schett G, Emery P, Tanaka Y, et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016;75:1428- 37. doi: 10.1136/annrheumdis-2016-20920

69. Nam JL, Villeneuve E, Hensor EM, et al: Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study). Ann Rheum Dis. 2014;73:75-85. doi: 10.1136/annrheumdis-2013-203440

70. Smolen JS, Aletaha D. Rheumatoid arthritis therapy reappraisal: straregies, opportunities and challenges. Nat Rev Rheumatol. 2015 May;11(5):276-89. doi: 10.1038/nrrheum.2015.8. Epub 2015 Feb 17.

71. Cuppen BV, Welsing PM, Sprengers JJ, et al. Personalized biological treatment for rheumatoid arthritis: a systematic review with a focus on clinical applicability. Rheumatology (Oxford). 2016;55:826-39. doi: 10.1093/rheumatology/kev421

72. Насонов ЕЛ. Ревматоидный артрит: проблемы и значение персонифицированной медицины. Терапевтический архив. 2012;84:5-10 [Nasonov EL. Rheumatoid arthritis: the problem and the importance of personalized medicine. Terapevticheskii Arkhiv. 2012;84:5- 10 (In Russ.)].

73. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheum. 2016;68:1-26. doi: 10.1002/art.39489

74. Насонов ЕЛ. Фармакотерапия ревматоидного артрита: российские и международные рекомендации. Научно- практическая ревматология. 2016;54(5):557- 71 [Nasonov EL. Pharmacotherapy for rheumatoid arthritis: Russian and International guidelines. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(5):557-71 (In Russ.)]. doi: 10.14412/1995-4484-2016-557-571

75. Jorgensen TS, Tarp S, Furst DE, et al. Added-value of combining methotrexate with a biological agent compared to biological monotherapy in patients with rheumatoid arthritis: a systemic review and meta-analysis of randomized trials. Ann Rheum Dis. 2015;74 Suppl 2:239. doi: 10.1136/annrheumdis-2015-eular.3396

76. Choy E, Aletaha D, Behrens F, et al. Monotherapy with biologic disease-modifying anti- rheumatic drugs in rheumatoid arthritis. Rheumatology (Oxford). 2016 Aug 21. pii: kew271 [Epub ahead of print].


Рецензия

Для цитирования:


Насонов Е.Л. Биоаналоги в ревматологии. Научно-практическая ревматология. 2016;54(6):628-640. https://doi.org/10.14412/1995-4484-2016-628-640

For citation:


Nasonov E.L. BIOSIMILARS IN RHEUMATOLOGY. Rheumatology Science and Practice. 2016;54(6):628-640. (In Russ.) https://doi.org/10.14412/1995-4484-2016-628-640

Просмотров: 1400


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 1995-4484 (Print)
ISSN 1995-4492 (Online)