Новые рекомендации по лечению ревматоидного артрита (EULAR, 2013): место глюкокортикоидов

Несмотря на большие достижения в лечении ревматоидного артрита (РА), связанные с разработкой новых методов ранней диагностики, внедрением в клиническую практику широкого спектра инновационных лекарственных препаратов и особенно совершенствованием стратегии их применения, глюкокортикоиды (ГК) по-прежнему остаются важнейшим компонентом фармакотерапии этого заболевания в реальной клинической практике. В данной публикации, которая является продолжением серии статей, посвященных обсуждению основных положений рекомендаций Европейской антиревматической лиги (EULAR) 2013 г., касающихся лечения раннего РА, речь пойдет о месте ГК. Анализ имеющихся данных свидетельствует о том, что применение ГК при РА следует зарезервировать за пациентами с высокой активностью воспалительного процесса, имеющими факторы, которые ассоциируются с неблагоприятным прогнозом, но при отсутствии факторов риска нежелательных реакций (НР) и, разумеется, противопоказаний для терапии ГК. В течение всего времени применения ГК необходим тщательный мониторинг НР, который следует проводить согласно рекомендациям EULAR. Предполагается, что более широкое применение комбинированной терапии метотрексатом и ГК на ранней стадии РА позволит улучшить прогноз, по крайней мере у части пациентов, и добиться существенного снижения «стоимости» болезни, за счет как уменьшения риска инвалидности, так и потребности в назначении дорогостоящих генно-инженерных биологических препаратов и протезировании суставов. Все это вместе взятое подтверждает актуальность включения положения о возможности применения ГК в Рекомендации по лечению ревматоидного артрита Общероссийской общественной организации «Ассоциация ревматологов России» (2014).

1. Van der Goes MC, Jacobs JW, Bijsma JW. The value of glucocorticoid co-therapy in different rheumatic diseases – positive and adverse effects. Arthritis Res Ther. 2014;16 (Suppl 2):S2. 8. doi: 10.1186/ar4686

2. Kavanaugh A, Wells AF. Benefits and risks of low-dose glucocorticoid treatment in the patient with rheumatoid arthritis. Rheumatology (Oxford). 2014;53:1742–51. doi: 10.1093/rheumatology/keu135. Epub 2014 Apr 10.

3. Pope JE, Hong P, Koehler BE. Prescribe trends in disease modifying antirheumatic drugs for rheumatoid arthritis: a survey of practicing Canadian rheumatologist. J Rheumatol. 2002;29:255–60.

4. Thiele K, Buttgereit F, Huscher D, Zink A. Current use of 9. glucocorticoids in patients with rheumatoid arthritis in Germany. Arthritis Rheum. 2005;53:740–7. doi: 10.1002/art.21467

5. Sokka T, Kautiainen N, Toloza S, et al. QUEST-RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries. Ann Rheum Dis. 2007;66:1491–6. doi: 10.1136/ard.2006.069252

6. Fardet L, Petersen I, Nazareth I. Prevalence of long-term oral glucocorticoid prescriptions in UK over the past 20 years. 10. Rheumatology (Oxford). 2011;50:1982–90. doi: 10.1093/rheumatology/ker017. Epub 2011 Mar 10.

7. Andre V, Le Goff B, Leux C, et al. Information on glucocorticoid therapy in the main studies of biological agents. Joint Bone Spain. 2011;78:478–83. doi: 10.1016/j.jbspin.2011.01.001. Epub 2011 Feb 22.

8. 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. Nauchnoprakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(6):609–22 (In Russ.)]. doi: 10.14412/19954484-2013-609-22

9. Насонов ЕЛ, Каратеев ДЕ, Чичасова НВ. Новые рекомендации по лечению ревматоидного артрита (EULAR, 2013): место метотрексата. Научнопрактическая 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

10. 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

11. Buttgereit F, Straub RH, Wehling M, et al. Standartised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis. 2002;61:718–22. doi: 10.1136/ard.61.8.718

12. 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

13. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum (Arthritis Care Res). 2008;59:762–84. doi: 10.1002/art.23721

14. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64:625–39. doi: 10.1002/acr.21641

15. Singh JA, Saag KG, Furst DE, et al. Reply. Arthritis Care Res (Hoboken). 2012;64:1623–4. doi: 10.1002/acr.21769

16. National Institute for Clinical Excellence (NICE). Rheumatoid arthritis: The management of rheumatoid arthritis in adults: NICE clinical guidance 79; 2009. [Internet. Accessed July 14, 2011.] Available from: http://www.nice.org.uk/nicemedia/pdf/CG79NICEGuideline.pdf

17. Luqmani R, Hennel S, Estrach C, et al., on Behalf of the British Society for Rheumatology and British Health Professionals in Rheumatology Standards, Guidelines and Audit Working Group. British Society for Rheumatology and British Health Professionals in Rheumatology Guideline for the Management of Rheumatoid Arthritis (after the first 2 years). Rheumatology. 2009;48:436–9. doi: 10.1093/rheumatology/key450a

18. Bykerk VP, Akhavan P, Hazlewood GS, et al. Canadian Rheumatology Association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol. 2012;39:1559–82. doi: 10.3899/jrheum.110207

19. Baecklund E, Forsblad d’Elia H, Turesson K. Guidelines for the pharmaceutical management of rheumatoid arthritis Swedish Society of Rheumatology, April 14, 2011. Available from: http://www.svenskreumatologi.se/index2.htm

20. Da Mota LMH, Cruz BA, Brenol CV, et al. 2012 Brazilian Society of Rheumatology Consensus for the treatment of rheumatoid arthritis. Rev Bras Rheumatol. 2012;52:135–74.

21. Mouterde G, Dernis E, Ruyssen-Witrand A, et al. Indications of glucocorticoids in early arthritis and rheumatoid arthritis: recommendations for clinical practice based on data from literature and expert opinion. Joint Bone Spain. 2010;77:597–603. doi: 10/1016/j.jbspin.2009.12.011

22. Criswell LA, Saag KG, Sems KM, et al. Moderate-term, lowdose corticosteroids for rheumatoid arthritis. Cochrane Database Syst Rev. 2000;2:CD001158.

23. Gotzsche PC, Johansen HK. Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Cochrane Database Syst Rev. 2004;3:CD000189.

24. Boers M, Verhoeven AC, Markusse HM, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997;350:309–18. doi: 10.1016/S0140-6736(97)01300-7

25. Hansen M, Podenphant J, Florescu A, et al. A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects. Ann Rheum Dis. 1999;58:713–8. doi: 10.1136/ard.58.11.713

26. Van Everdingen AA, Jacobs JW, Siewertsz-van Reesema DR, Bijlsma JW. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, diseasemodifying properties, and side effects: a randomized, doubleblind, placebo-controlled clinical trial. Ann Intern Med. 2002;136:1–12. doi: 10.7326/0003-4819-136-1-20020101000006

27. Svensson B, Boonen A, Albertsson K, et al. Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial. Arthritis Rheum. 2005;52:3360–70. doi: 10.1002/art.21298

28. Wassenberg S, Rau R, Steinfeld P, Zeidler H. Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52:3371–80. doi: 10.1002/art.21421

29. Choy EH, Smith CM, Farewell V, et al. Factorial randomised controlled trial of glucocorticoids and combination disease modifying drugs in early rheumatoid arthritis. Ann Rheum Dis. 2008;67:656–63. doi: 10.1136/ard.2007.076299

30. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007;146:406–15. doi: 10.7326/0003-4819-146-6-20070320000005

31. Baker M, Jacobs JWG, Welsing PMJ, et al. Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis. Ann Intern Med. 2012;156; 329–39. doi: 10.7326/0003-4819-156-5-201203060-00004

32. Kirwan JR, Bijlsma JW, Boers M, Shea BJ. Effects of glucocorticoids on radiological progression in rheumatoid arthritis. Cochrane Database Syst Rev. 2007;(1):CD006356.

33. Graudal N, Jurgens G. Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled studies, including 112 comparisons. Arthritis Rheum. 2010;62:2852–63. doi: 10.1002/art.27592

34. Graudal N, Hubeck-Graudal T, Tarp S, et al. Effect of combination therapy on joint destruction in rheumatoid arthritis: a network meta-analysis of randomized controlled trials. PLoS ONE. 2014;9:e106408. doi: 10.1371/journal.pone.0106408

35. Gorter SL, Bijlsma JW, Cutolo M, et al. Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systemic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2010;69:1010–4. doi: 10.1136/ard.2009.127332

36. Gaujoux-Viala C, Nam JL, Ramiro S, et al. Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib — a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2014;73:510–5. doi: 10.1136/annrheumdis-2013-204588

37. Hafstrom I, Albertsson K, Boonen A, et al. Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study. Ann Rheum Dis. 2009;68:508–513. doi: 10.1136/ard.2008.087833

38. Jacobs JW, van Everdingen AA, Verstappen SM, Bijlsma JW. Follow-up radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy or placebo. Arthritis Rheum. 2006;54:1422–8. doi: 10.1002/art.21809

39. Landewe RB, Boers M, Verhoeven AC, et al. COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention. Arthritis Rheum. 2002;46:347–56. doi: 10.1002/art.10083

40. Van Tuyl LHD, Boers M, Lems WF, et al. Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis. Ann Rheum Dis. 2010;69:807–12. doi: 10.1136/ard.2009.108027

41. 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):477–494 [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):477–494 (In Russ.)]. doi: 10.14412/1995-44842014-477-494

42. Насонов ЕЛ. Лечение ревматоидного артрита 2012: место метотрексата. Научно-практическая ревматология. 2012;51(приложение):1–24 [Nasonov EL. Treatment of rheumatoid arthritis 2012: place of methotrexate. Nauchnoprakticheskaya revmatologiya = Rheumatology Science and Practice. 2012;51(Suppl):1–24 (In Russ.)].

43. Goekoop-Ruiterman YPM, 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). Arthritis Rheum. 2005;52:3381–90. doi: 10.1002/art.21405

44. Klarenbeek NB, Guler-Yuksel M, van der Kooij SM, et al. The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis. 2011;70:1039–46. doi: 10.1136/ard.2010.141234

45. Markusse IM, Akdemir G, van den Broek M, et al. 10 year of treat-to-target therapy in rheumatoid arthritis patients (the BeST study): clinical and radiological outcome. Arthritis Rheum. 2013;65 Suppl: S620.

46. Montecucco C, Todoerti M, Sakellariou G, et al. Low-dose oral prednisolon improves clinical and ultrasonographic remission rates in early rheumatoid arthritis: results of a 12month open-label randomized study. Arthritis Res Ther. 2012;14:R112. doi: 10.1186/ar3838

47. Wevers-de Boer K, Visser K, Heimans L, et al. Remission induction therapy with methotrexate and prednisolon in patients with early rheumatoid and indifferentiated arthritis (the IMPROVED study). Ann Rheum Dis. 2012;71:1472–7. doi:10.1136/annrheumdos-2011;-200736

48. Nam JR, Villeneuve E, Hensor EME, et al. Remission induction comparing infliximab and high-dose intravenous steroids, followed by treat-to target: a double-blind, randomized, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study). Ann Rheum Dis. 2013. doi: 10.1136/annrheumdis-2013-2034440

49. Leirisalo-Repo M, Kautinen H, Laasonen L, et al. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2 year results from an investigator-initiated, randomized, double-blind, placebo-controlled study (the NEORACo Study). Ann Rheum Dis. 2013;72: 851–7. doi: 10.1136/annrheumdis-2012-201365

50. Rantalaiho V, Kautianen H, Korpela M, et al. Targeted treatment with a combination of traditional DMARDs produces excellent clinical and radiographic long-term outcomes in early rheumatoid arthritis regardless of initial infliximab. The 5-tear follow-up results of a randomized clinical trial, the NEO-RACo trial. Ann Rheum Dis. 2013. doi: 10.1136/annrheumdis-2013-203497

51. Den Uyl D, ter Wee M, Boers M, et al. A non-inferiority trial of an attenuated combination strategy (COBRA-light) compared to the original COBRA strategy: clinical results after 26 weeks. Ann Rheum Dis. 2014;73:1071–8. doi: 10.1136/annrheumdis-2012-202818

52. Van Tuyl LH, Plass AM, Lems WF, et al. Why are Dutch rheumatologist reluctant to use the COBRA treatment strategy in early rheumatoid arthritis? Ann Rheum Dis. 2007;66:974–6. doi: 10.1136/ard.2006.067447

53. De Jong PH, Hazes JM, Barenndregt PJ, et al. Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. Ann Rheum Dis. 2013;72:72–8. doi:10.1136/annrheumdis2011-201162

54. De Jong PH, Hazes JM, Han HK, et al. Randomized comparison of initial triple DMAR therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial. Ann Rheum Dis. 2014;73:1331–9. doi:10.1136/annrheumdis-2013-204788

55. De Jong PH, Quax RA, Huisman M, et al. Response to glucocorticoids at 2 weeks predicts the effectiveness of DMARD induction therapy at 3 months: post hoc analysis from the tREACH study. Ann Rheum Dis. 2013;72:1659–63. doi: 10.1136/annrheumdis-2012-202152

56. De Rotte MC, de Jong PH, Quax RA, et al. Glucocorticoids and methotrexate have a synergistic working on decrease of rheumatoid arthritis disease activity. Ann Rheum Dis. 2013;72 Suppl:S396. doi: 10.1136/annrheumdis-2013-eular.1207

57. Verschueren P, de Cock D, Corlue L, et al. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-tohigh-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial. Ann Rheum Dis. 2015;74:27–34. doi: 10.1136/annrheumdis-2014-205489

58. Verschueren P, de Cock D, Corlue L, et al. Patients lacking classical poor prognostic markers might also benefit from a step-down glucocorticoid bridging scheme in early rheumatoid arthritis: week 16 results from the randomized multicenter CareRA trial. Arthritis Res Ther. 2015:17:29. doi: 0rg/10.1186/s13075-015-0611-8

59. Gaujoux-Viala C, Mitrovic S, Barnetche T, et al. Efficacy of glucocorticoids for early rheumatoid arthritis (RA): a metaanalysis of randomized controlled trials. Ann Rheum Dis. 2014;73 Suppl 2:S218. doi: 10.1136/annrheumdis-2014eular.5840

60. Volkman ER, Rezai S, Tarp S, et al. We still don’t` know how to taper glucocorticoids in rheumatoid arthritis, and we can do better. J Rheumatol. 2013;40:10. doi: 10.3899/jrheum.130019

61. Caporali R, Scire CA, Todoerti M, Montecucco C. The role of low-dose glucocorticoids for rheumatoid arthritis in biologic era. Clin Exp Rheumatol. 2013;31 Suppl 78: S9–13.

62. Tenga G, Goeb V, Daveau R, et al. Impact des biotherapies sur la douleur, l’activite de la maladie, la gene fonctionnelle et la prise de corticoides dans une file active de malades atteints de polyarthrite rhumatoide. Rev Rhum. 2006;73:1096–7. doi: 10.1016/j.rhum.2006.10.184

63. Seror R, Dougados M, Gossec L. Glucocorticoid sparing effect of tumour necrosis factor alpha inhibitors in rheumatoid arthritis in real life practice. Clin Exp Rheumatol. 2009;27:807–13.

64. Nilsson AC, Christensen AF, Junker P, Lindegaard HM. Tumor necrosis factor-alpha inhibitors are glucocorticoidsparing in rheumatoid arthritis. Dan Med Bull. 2011;58:A4257.

65. Naumann L, Huscher D, Detert J, et al. Anti-tumor necrosis factor α therapy in patients with rheumatoid arthritis results in a significant and long-lasting decrease of concomitant glucocorticoid treatment. Ann Rheum Dis. 2009;68:1934–6. doi: 10.1136/ard.2009.111807

66. Nishimoto N, Miyasaka N, Yamamoto K, et al. Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis. 2009;68:1580–4. doi: 10.1136/ard.2008.092866

67. Fortunet C, Pers Y-M, Lambert J, et al. Tocilizumab induces corticosteroid sparing in rheumatoid arthritis patients in clinical practice. Rheumatology (Oxford). 2015;54:672–7. doi: 10.1093/rheumatology/keu339

68. Saraux A, Rouanet S, Flipo R-M, et al. Description of glucocorticoid sparing effect in rheumatoid arthritis treated by tocilizumab in real life: an interim analysis of the SPARE-1 study. Ann Rheum Dis. 2013;72 Suppl3:618. doi: 10.1136/annrheumdis-2013-eular.1837

69. Tanaka Y, Takeuchi T, Mimori T, et al. Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. Ann Rheum Dis. 2010;69:1286–91. doi: 10.1136/ard.2009.121491

70. Harigani M, Takeuchi T, Tanaka Y, et al. Discontinuation of adalimumab treatment in rheumatoid arthritis patients after achieving low disease activity. Mod Rheumatol. 2012;22:814–22. doi: 10.3109/s10165-011-0586-5

71. Kavanaugh A, Emery P, Fleischmann R, et al. Withdrawal of adalimumab in early rheumatoid arthritis patients who attained stable low disease activity with adalimumab plus methotrexate: results of a phase 4, double-blind, placebo-controlled trial. Rheumatology. 2012;51 Suppl. 3:iii29–iii30.

72. Насонов ЕЛ, Чичасова НВ, Ковалев ВЮ. Глюкокортикоиды в ревматологии. Москва; 1998. 160 с. [Nasonov EL, Chichasova NV, Kovalev VYu. Glukokortikoidy v revmatologii [Glucocorticoids in rheumatology]. Moscow; 1998. 160 p.]

73. Da Silva JA, Jacobs JW, Kirwan JR, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis. 2006;65:285–93. doi: 10.1136/ard.2005.038638

74. Hoes JN, Jacobs JWG, Boers M, et al. EULAR evidence based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis. 2007;66:1560–7. doi: 10.1136/ard.2007072157

75. Dixon WG, Bansback N. Understanding the side effects of glucocorticoid therapy: shining a light on a drug everyone thinks they know. Ann Rheum Dis. 2012;71:1761–4. doi: 10.1136/annrheumdis-2012-202021

76. Caplan L, Wolfe F, Russel AS, et al. Corticosteroids use in rheumatoid arthritis: prevalence, predictors, correlates, and outcome. J Rheumatology. 2007;34:696–706.

77. Чичасова НВ. Рекомендации EULAR по лечению ревматоидного артрита (2013): использование глюкокортикоидов. Современная ревматология. 2014;(2):28–34 [Chichasova NV. EULAR recommendation for the management of rheumatoid arthritis (2013): glucocorticoid use. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2014;(2):28–34. (In Russ.)]. doi: 10.14412/1996-7012-2014-2-28-34

78. Skeoch S, Bruce IN. Atherosclerosis in rheumatoid arthritis: is it all about inflammation? Nat Rev Rheumatol. 2015 Mar 31. doi: 10.1038/nnrheum.2015.40. [Epub ahead of print].

79. Huscher D, Thiele K, Gromnica-Ihle E, et al. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis. 2009;68:1119–24. doi: 10.1136/ard.2008.092163

80. Strangfeld A, Everslage M, Schneider M, et al. Treatment benefit or survival of the fittest: what drives the timedependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patients? Ann Rheum Dis. 2011;70:1941–20. doi: 10.1136/ard.2011.151043

81. Dixon WG, Suissa S, Hudson M. The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: systemic review and meta-analysis. Arthritis Res Ther. 2011;13:R139. doi: 10.1186/ar3453

82. Tarp S, Bartels EM, Kirwan JR, et al. Adverse effects of glucocorticoid therapy in rheumatoid arthritis (RA): a systemic review and meta-analysis of randomized controlled trials. Ann Rheum Dis. 2013;71:207–8. doi: 10.1136/annrheumdis-2012eular.2119

83. Mitrovic S, Farder L, Vatier C, et al. Safety of glucocorticoids for early rheumatoid arthritis: a meta-analysis of randomized controlled trials. Ann Rheum Dis. 2014;73 Suppl 2:S228. doi: 10.1136/annrheumdis-2014-eular.5481

84. Roubille C, Richer V, Startino T, et al. The effect of tumor necrosis factor inhibitors, methotrexate, non-steroidal antiinflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systemic review and meta-analysis. Ann Rheum Dis. 2015;74:480–9. doi: 10.1136/annrheumdis-2014-206623

85. Ajeganova S, Svensson B, Hafstrom I, on behalf of the BARFOT Study Group. Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomized trial. BMJ Open. 2014;4:e004259. doi: 10.1136/bmjopen-2013-004259

86. Avina-Zubieta JA, Abrahamowicz M, Choi HK, et al. Risk of cerebrovascular disease associated with the use of glucocorticoids in patients with incident rheumatoid arthritis: a population-based study. Ann Rheum Dis. 2010;70:990–5. doi: 10.1136/ard.2010.140210

87. Den Uyl D, van Raalte DH, Nurmohamed MT, et al. Metabolic effects of high-dose prednisolone treatment in early rheumatoid arthritis: balance between diabetogenic effects and inflammation reduction. Arthritis Rheum. 2012;64:639–46. doi: 10.1002/art.33378

88. Hoes JN, van der Goes MC, van Raalte DH, et al. Glucose tolerance, insulin sensitivity and beta-cell function in patients with rheumatoid arthritis treated with or without low-tomedium dose glucocorticoids. Ann Rheum Dis. 2011;70:1887–94. doi: 10.1136/ard.2011.151464

89. Jurgens MS, Jacobs JW, Geenen R, et al. Increase of body mass index in a tight controlled methotrexate-based strategy with prednisone in early rheumatoid arthritis: side effect of the prednisone or better control of disease activity? Arthritis Care Res (Hoboken). 2013;65:88–93. doi: 1002/acr.21797

90. Younis S, Rosner I, Boulman N, et al. Weight change during pharmacological blockade of interleukin-6 or tumor necrosis factor-α in patients with inflammatory rheumatic disorders: a 16-week comparative study. Cytokine. 2013;61:353–5. doi: 10.1016/j.cyto.2012.11.07

91. Kanis JA, Johnell O, Re Laert C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone. 2004;35:375–82. doi: 10.1016/j.bone.2004.03.024

92. Van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteop Int. 2002;13:777–87. doi: 10.1007/s001980200108

93. Ghazi M, Kolta S, Briot K, et al. Prevalence of vertebral fractures in patients with rheumatoid arthritis: revisting the role of glucocorticoids. Osteop Int. 2012;23:581–7. doi: 10.1007/s00198-011-1584-3

94. Siu S, Haraoui B, Bissonnette R, et al. A meta-analysis of tumor necrosis factor inhibitors and glucocorticoids on bone density in rheumatoid arthritis and ankylosing spondylitis trials. Arthritis Care Res. 2014 Nov 21. doi: 10.1002/acr.22519. [Epub ahead of print].

95. Van der Goes MC, Jacobs JWG, Jurgens MS, et al. Are changes in bone mineral density different between groups of early rheumatoid arthritis patients treated according to a tight control strategy with or without prednisone if osteoporosis prophylaxis is applied? Osteop Int. 2013;24:1429–36. doi: 10.1007/s00198-012-2073-z

96. Dinsen S, Baslund B, Klose M, et al. Why glucocorticoid withdrawal may sometimes be as dangerous as the treatment itself. Eur J Internal Med. 2013;24:714–20. doi: 10.1016/j.ejim.2013.05.014

97. Pincus T, Swearingen CJ, Luta G, Sokka T. Efficacy of prednisolon 1–4 mg/day in patients with rheumatoid arthritis: a randomized, double-blind, placebo controlled withdrawal clinical trial. Ann Rheum Dis. 2009;68:1715–20. doi: 10.1136/ard.2008.095539

98. Tengstand B, Larsson E, Klareskog L, Hafstrom I. Randomized withdrawal of long-term prednisone treatment in rheumatoid arthritis: effects on inflammation and bone mineral density. Scand J Rheumatol. 2007;36:351–8. doi: 10.1080/03009740701394021

99. Tanaka Y, Hirata S. Intensive intervention can lead to a treatment holiday from biological DMARDs in patients with rheumatoid arthritis. Drug. 2014;74:2129–39. doi: 10.1007/s40265-014-0323-4

100. Van Herwaarden N, den Broeder AA, Jacobs W, et al. Downtitration and discontinuation strategies of tumor necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity (review). The Cochrane collaboration. 2014;9. [Epub 2014 Sep 29].

101. Del Rincon I, Battafarano DF, Restrepo JF, et al. Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis. Arthritis Rheum. 2014;66:264–72. doi: 10.1002/art.38210

102. Listing J, Kekow J, Manger B, et al. Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFα inhibitors and rituximab. Ann Rheum Dis. 2015;74:415–21. doi: 10.1136/annrheumdis-2013-204021

103. Markusse IM, Dirven L, van Groenendael JH, et al. Mortality in a large cohort of patients with early rheumatoid arthritis that were treated-to-target for 10 years. Arthritis Rheum. 2014;Suppl: S359.

104. Pincus T. Mortality – the neglected outcome in rheumatic diseases? Arthritis Care Res. 2015. doi: 10.1002/acr.22554

105. Humphreys JH, Warner A, Chipping J, et al. Mortality trends in patients with early rheumatoid arthritis over 20 years: results from the Norfolk Arthritis Register. Arthritis Care Res. 2014;66:1296–301. doi: 10.1002/acr.22296

106. Vermeer M, Kuper HH, Hoekstra M, et al. Implementation of a Threat-to-Target strategy in very early rheumatoid arthritis. Results of the Dutch Rheumatoid Arthritis Monitoring Remission Induction Cohort Study. Arthritis Rheum. 2011;63:2865–72. doi: 10.1002/art.30494

107. Vermeer M, Kuper HH, Bernelot Moens HJ, et al. Sustained beneficial effects of a protocolized treat-to-target strategy in very early rheumatoid arthritis: three year results of the DREAM remission induction cohort. Arthritis Care Res. 2013;65:1219–26. doi: 10.1002/acr.21984

108. Nam JL, Villeneuve E, Hensor EM, et al. A randomized controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial. Ann Rheum Dis. 2014;73:1027–36. doi: 10.1136/annrheumdis2013-204882

109. Baschant U, Lane NE, Tuckermann J. The multiple facets of glucocorticoid action in rheumatoid arthritis. Nat Rev Rheumatol. 2012;8:645–55. doi: 10.1038/nrrheum.2012.166

110. Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. Lancet. 2009;373:1905–17. doi: 10.1016/S0140-6736(09)60326-3

111. Dejager L, Vandevyver S, Petta I, Libert C. Dominance of the strongest: inflammatory cytokines versus glucocorticoids. Cytokine Growth Factor Rev. 2014;25:21–31. doi: 10.1016/j.cytogfr.2013.12.006

112. Cribbs AP, Kennedy A, Penn H, et al. Methotrexate restores regulatory T cell function through demethylation of the foxp3 upstream enhancer in patients with RA. Arthritis Rheum. 2015 May;67(5):1182–92. doi: 10.1002/art.39031

113. De Paz B, Prado C, Alperi-Lopez M, et al. Effects of glucocorticoid treatment on CD25-FOXP3+ population and cytokine-producing cells in rheumatoid arthritis. Rheumatology. 2012;51:1198–207. doi: 10.1093/rheumatology/kes039

114. Насонов ЕЛ, Александрова ЕН, Авдеева АС, Рубцов ЮП. Т-регуляторые клетки при ревматоидном артрите. Научно-практическая ревматология.2014;52(4):430–7 [Nasonov EL, Aleksandrova EN, Avdeeva AS, Rubtsov YuP. T regulatory cells in rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2014;52(4):430–7 (In Russ.)]. doi: 10.14412/1995-4484-2014430-437

115. Trampisch US, Krause D, Trampisch HJ, et al. Comparison of the efficacy and safety of two starting dosages of prednisolone in early active rheumatoid arthritis (CORRO): study protocol for a randomized controlled trial. Trials. 2014;15:344l. doi: 10.1186/1745-6215-15-344

116. Van der Goes MC, Jacobs JW, Boers M, et al. Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice. Ann Rheum Dis. 2010;69:1913–9. doi: 10.1136/ard.2009.124958

117. Duru N, van der Goes MC, Jacobs JW, et al. EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis. 2013;72:1905–13. doi: 10.1136/annrheumdis-2013-203249

118. Van der Goes MC, Jacobs JW, Boers M, et al. Patient and rheumatologist perspectives on glucocorticoids: an exercise to improve the implementation of the European League Against Rheumatism (EULAR) recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis. 2010;69:1015–21. doi: 10.1136/ard.2009.114579

119. Cipriani P, Ruscitti P, Carubbi F, et al. Methotexate in rheumatoid arthritis: optimizing therapy among different formulation. Current and Emerging paradigm. Clin Ther. 2014;36:427–35. doi: 10.1016/j.clinthera.2014.01.014

120. Jay R. Methotrexate revisit: considerations for subcutaneous administration in RA. Clin Rheumatol. 2015;34:201–5. doi: 10.1007/s10067-014-2830-9

121. 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.

122. Boyman O, Comte D, Spertini F. Adverse reactions to biologic agents and their medical management. Nat Rev Rheumatol. 2014;10:612–27. doi: 10.1038/nrrheuum.2014.123

123. Wailoo A, Alava MH, Scott IC, et al. Cost-effectiveness of treatment strategies using combination disease-modifying anti-rheumatic drugs and glucocorticoids in early rheumatoid arthritis. Rheumatology. 2014;53:1773–7. doi: 10.1093/rheumatology/key039