Несмотря на достигнутые успехи в лечении ревматоидного артрита (РА), связанные с разработкой новых лекарственных препаратов и совершенствованием стратегии лечения, позволяющих достигнуть ремиссии у многих пациентов, остается много теоретических и клинических проблем, касающихся как определения понятия «ремиссия», ее характеристики и типов, так и подходов к оптимальной тактике «симптоматической» и «патогенетической» лекарственной терапии на разных стадиях болезни, применение которой позволит быстро индуцировать состояние ремиссии и поддерживать ее в долгосрочной перспективе. Необходимы дальнейшие исследования, направленные на изучение природы гетерогенности патогенетических механизмов РА, подходов к ранней диагностике, совершенствование методов мониторинга активности заболевания, биомаркеров эффективности и резистентности к терапии и, наконец, разработки дифференцированной терапии, в том числе связанной с поиском новых «терапевтических» мишеней.
Ключевые слова: ревматоидный артрит, ремиссия, рефрактерность, ингибиторы JAK киназы.
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Success in a treatment of rheumatoid arthritis (RA), associated with a development of new medications and improving treatment strategies, allows to achieve remission in many patients. Despite this a lot of theoretical and clinical issues remain, including a definition of the term "remission", its characteristics and types as well as approaches to optimal tactics of "symptomatic" and "pathogenetic" drug therapy at different stages of the disease. Use of a such tactics will allow to induce quickly a state of remission and maintain it for a long term. Further research is needed which should be directed to investigation of a heterogeneity of RA pathogenetic mechanisms and to elaboration of approaches to its early diagnosis as well as to improving methods for monitoring a disease activity, biomarkers of efficacy and resistance to therapy, and finally, to developing of a differentiated therapy, including a search for new “therapeutic” targets.
Keywords: rheumatoid arthritis, remission, refractoriness, JAK kinase inhibitors.
Список литературы
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22. Buch MH. Defining refractory rheumatoid arthritis. Ann Rheum Dis. 2018;77:966-9. doi:10.1136/annrheumdis-2017-212862
23. de Hair MJH, Jacobs JWG, Schoneveld JLM, et al. Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology. 2017. doi:10.1093/ rheumatology/kex349
24. Kearsley-Fleet L, De Cock D, Watson K, et al. Refractory disease in rheumatoid arthritis: results from the British society of rheumatology biologics register for rheumatoid arthritis. Arthritis Rheumatol. 2017;69.
25. Smolen JS, Aletaha D. Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges. Nat Rev Rheumatol. 2015 May;11(5):276-89. doi: 10.1038/ nrrheum.2015.8
26. Lee YC, Frits ML, Iannaccone CK, et al. Subgrouping of patients with rheumatoid arthritis based on pain, fatigue, inflammation, and psychosocial factors. Arthritis Rheumatol. 2014;66:2006-14. doi:10.1002/art.38682
27. Haliloglu S, Carlioglu A, Akdeniz D, Karaaslan Y, Kosar A. Fibromyalgia in patients with other rheumatic diseases: prevalence and relationship with disease activity. Rheumatol Int. 2014;34:1275-80.
28. Atzeni F, Cazzola M, Benucci M, et al. Chronic widespread pain in the spectrum of rheumatological diseases. Best Pract Res Clin Rheumatol. 2011;25:165-71.
29. Mian AN, Chaabo K, Wajed J, et al. Rheumatoid arthritis patients with fibromyalgic clinical features have significantly less synovitis as defined by power Doppler ultrasound. BMC Musculoskelet Disord. 2016;17:404.
30. Unger M, Alasti F, Supp G, Smolen JS, Aletaha D. The good, the bad and the ugly – refractory rheumatoid arthritis in 2016. Arthritis Rheumatol. 2016;68(Suppl 10): Abstract No. 3015. http://acrabstracts.org/abstract/the-good-the-bad-and-the-ugly-refractory-rheumatoid-arthritis-in-20...
31. Orange DE, Agius P, DiCarlo EF, Robine N, Geiger H, et al. Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning Integration of Synovial Histologic Features and RNA Sequencing Data. Arthritis Rheumatol. 2018;70(5):690-701. doi: 10.1002/art.40428
32. Basu N, Kaplan CM, Ichesco E, et al. Neurobiological features of fibromyalgia are also present amond rheumatoid arthritis patients. Arthritis Rheumatol. 2018 Feb 13. doi: 10.1002/art.40451
33. George M, Baker JF. The obesity epidemic and consequences for rheumatoid arthritis care. Curr Rheumatol Rep. 2016;18:6.
34. Pasma A, van Spijker A, Hazes JMW, Busschbach JJV, Luime JJ. Factors associated with adherence to pharmaceutical treatment for rheumatoid arthritis patients: a systematic review. Semin Arthritis Rheum. 2013;43:18-28.
35. Romão VC, Vital EM, Fonseca JE, et al. Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis? Arthritis Res Ther. 2017;19:1-13. doi:10.1186/s13075-017-1445-3
36. Schaeverbeke T, Truchetet ME, Kostine M, et al. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology. 2016;55: 210-20.
37. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843-62. doi: 10.1038/nrd.2017.201
38. Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects. Drugs. 2017;77(5):521-46. doi: 10.1007/s40265-017-0701-9
39. Gadina M, Johnson C, Schwartz D, Bonelli M, Hasni S, et al. Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs. J Leukoc Biol. 2018;104(3):499-514. doi: 10.1002/JLB.5RI0218-084R
40. Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-77. doi: 10.1136/annrheumdis-2016-210715
41. Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1-26. doi: 10.1002/art.39480
42. Smolen JS, van der Heijde D, Machold KP, Aletaha D, Landewé R. Proposal for a new nomenclature of disease-modifying antirheumatic drugs. Ann Rheum Dis. 2014;73(1):3-5. doi: 10.1136/annrheumdis-2013-204317
43. Al-Salama ZT, Scott LJ. Baricitinib: A Review in Rheumatoid Arthritis. Drugs. 2018 May;78(7):761-72. doi: 10.1007/s40265-018-0908-4
44. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374:1243-52.
45. Genovese MC, Kremer JM, Kartman CE, Schlichting DE, Xie L, et al. Response to baricitinib based on prior biologic use in patients with refractory rheumatoid arthritis. Rheumatology (Oxford). 2018 May 1;57(5):900-8. doi: 10.1093/rheumatology/kex 489
46. Schiff M, Kelly S, Le Bars M, Genovese M. Efficacy of abatacept in RA patients with an inadequate response to anti-TNF therapy regardless of reason for failure, or type or number of prior anti-TNF therapy used. Ann Rheum Dis. 2008;67(Suppl 2):337.
47. Smolen JS, Kay J, Doyle MK, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor α inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009;374:210-21.
48. Kremer JM, Tony H, Tak PP, Luggen M, Mariette X, Hessey E. Efficacy of ritumixab in active RA patients with an inadequate response to one or more TNF inhibitors. Ann Rheum Dis. 2006;65(Suppl 2):326.
49. Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017 Apr;17(4):233-47. doi: 10.1038/nri.2017.1
50. Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol. 2018;30(2):207-14. doi: 10.1097/BOR
51. McInnes IB, Buckley CD, Isaacs JD. Cytokines in rheumatoid arthritis – shaping the immunological landscape. Nat Rev Rheumatol. 2016 Jan;12(1):63-8. doi:10.1038/ nrrheum.2015.171
52. Conrad C, Di Domizio J, Mylonas A, Belkhodja C, Demaria O, et al. TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis. Nat Commun. 2018;9(1):25. doi: 10.1038/s41467-017-02466-4
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1. Ревматология. Российские клинические рекомендации. Под ред. Е.Л. Насонова. М.: ГЭОТАР-Медиа, 2017; 456 с. [Rheumatology. Russian clinical guidelines. Edited by E.L. Nasonov. M.: GEOTAR-Media, 2017; 456 p. (In Russ.)].
2. Аletaha D, Smolen JS. Diagnosis and Management of Rheumatoid Arthritis: A Review. JAMA. 2018 Oct 2;320(13):1360-72. doi: 10.1001/jama.2018.13103
3. McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389(10086):2328-37. doi: 10.1016/S0140-6736(17)31472-1
4. McGonagle D, Watad A, Savic S. Mechanistic immunological based classification of rheumatoid arthritis. Autoimmun Rev. 2018 Nov;17(11):1115-23. doi: 10.1016/j. autrev.2018.06.001
5. Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75:3-15.
6. van Vollenhoven R. Treat-to-target in rheumatoid arthritis - are we there yet? Nat Rev Rheumatol. 2019 Jan 30. doi: 10.1038/s41584-019-0170-5
7. Burmester GR, Pope JE. Novel treatment strategies in rheumatoid arthritis. Lancet. 2017;389(10086):2338-48. doi: 10.1016/S0140-6736(17)31491-5
8. Ajeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017;9(10):249-62. doi: 10.1177/1759720X17720366
9. Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K. Rheumatoid arthritis. Nat Rev Dis Primers. 2018 Feb 8;4:18001. doi: 10.1038/nrdp.2018.1
10. 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.
11. Olyunin YuA. Evaluation of disease activity in rheumatoid arthritis: recommendations and practice. Current rheumatology. 2014;2:15-20 (In Russ.).
12. Gaujoux-Viala C, Mouterde G, Baillet A, Claudepierre P, Fautrel B, Le Loët X, Maillefert JF. Evaluating disease activity in rheumatoid arthritis: which composite index is best? A systematic literature analysis of studies comparing the psychometric properties of the DAS, DAS28, SDAI and CDAI. Joint Bone Spain. 2012;79(2):149-55. doi: 10.1016/j.jbspin.2011.04.008
13. Ferreira RJO, Dougados M, Kirwan JR, Duarte C, et al. Drivers of patient global assessment in patients with rheumatoid arthritis who are close to remission: an analysis of 1588 patients. Rheumatology (Oxford), 2017;56(9):1573-8. doi: 10.1093/rheumatology/kex211
14. Nikiphorou E, Radner H, Chatzidionysiou K, et al. Patient global assessment in measuring disease activity in rheumatoid arthritis: a review of the literature. Arthritis Res Ther. 2016;18:251.
15. van Nies JA1, Krabben A, Schoones JW, Huizinga TW, Kloppenburg M, van der Helm-van Mil AH. What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? A systematic literature review. Ann Rheum Dis. 2014;73(5):861-70. doi: 10.1136/annrheumdis-2012-203130
16. Cook MJ, Diffin J, Scirè CA, Lunt M, MacGregor AJ, Symmons DP, Verstappen SM. Predictors and outcomes of sustained, intermittent or never achieving remission in patients with recent onset inflammatory polyarthritis: results from the Norfolk. Arthritis Register. 2016;55(9):1601-9. doi: 10.1093/rheumatology/kew210
17. Michelsen B, Kristianslund EK, Sexton J, Hammer HB, Fagerli KM, et al. Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR-DMARD study. Ann Rheum Dis. 2017;76(11):1906-10. doi: 10.1136/annrheumdis-2017-211284
18. Matcham F, Davies R, Hotopf M, Hyrich KL, Norton S, Steer S, Galloway J. The relationship between depression and biologic treatment response in rheumatoid arthritis: An analysis of the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2018;57(5):835-43. doi: 10.1093/rheumatology/kex528
19. Vittecoq O, Richard L, Banse C, Lequerré T. The impact of smoking on rheumatoid arthritis outcomes. Join Bone Spine. 2018;85(2):135-8. doi: 10.1016/j.jbspin. 2017. 12.004
20. Juan S, Jiabi Z. Impact of obesity on the efficacy of different biologic agents in inflammatory diseases: a systematic review and meta-analysis. Joint Bone Spine. 2018 Apr 7. pii: S1297-319X(18)30050-2. doi: 10.1016/j.jbspin.2018.03.007
21. Martin-Mola E, Balsa A, García-Vicuna R, Gómez-Reino J, González-Gay MA, Sanmartí R, Loza E. Anti-citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review. Rheumatol Int. 2016;36(8):1043-63. doi: 10.1007/s00296-016-3506-3
22. Buch MH. Defining refractory rheumatoid arthritis. Ann Rheum Dis. 2018;77:966-9. doi:10.1136/annrheumdis-2017-212862
23. de Hair MJH, Jacobs JWG, Schoneveld JLM, et al. Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology. 2017. doi:10.1093/ rheumatology/kex349
24. Kearsley-Fleet L, De Cock D, Watson K, et al. Refractory disease in rheumatoid arthritis: results from the British society of rheumatology biologics register for rheumatoid arthritis. Arthritis Rheumatol. 2017;69.
25. Smolen JS, Aletaha D. Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges. Nat Rev Rheumatol. 2015 May;11(5):276-89. doi: 10.1038/ nrrheum.2015.8
26. Lee YC, Frits ML, Iannaccone CK, et al. Subgrouping of patients with rheumatoid arthritis based on pain, fatigue, inflammation, and psychosocial factors. Arthritis Rheumatol. 2014;66:2006-14. doi:10.1002/art.38682
27. Haliloglu S, Carlioglu A, Akdeniz D, Karaaslan Y, Kosar A. Fibromyalgia in patients with other rheumatic diseases: prevalence and relationship with disease activity. Rheumatol Int. 2014;34:1275-80.
28. Atzeni F, Cazzola M, Benucci M, et al. Chronic widespread pain in the spectrum of rheumatological diseases. Best Pract Res Clin Rheumatol. 2011;25:165-71.
29. Mian AN, Chaabo K, Wajed J, et al. Rheumatoid arthritis patients with fibromyalgic clinical features have significantly less synovitis as defined by power Doppler ultrasound. BMC Musculoskelet Disord. 2016;17:404.
30. Unger M, Alasti F, Supp G, Smolen JS, Aletaha D. The good, the bad and the ugly – refractory rheumatoid arthritis in 2016. Arthritis Rheumatol. 2016;68(Suppl 10): Abstract No. 3015. http://acrabstracts.org/abstract/the-good-the-bad-and-the-ugly-refractory-rheumatoid-arthritis-in-20...
31. Orange DE, Agius P, DiCarlo EF, Robine N, Geiger H, et al. Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning Integration of Synovial Histologic Features and RNA Sequencing Data. Arthritis Rheumatol. 2018;70(5):690-701. doi: 10.1002/art.40428
32. Basu N, Kaplan CM, Ichesco E, et al. Neurobiological features of fibromyalgia are also present amond rheumatoid arthritis patients. Arthritis Rheumatol. 2018 Feb 13. doi: 10.1002/art.40451
33. George M, Baker JF. The obesity epidemic and consequences for rheumatoid arthritis care. Curr Rheumatol Rep. 2016;18:6.
34. Pasma A, van Spijker A, Hazes JMW, Busschbach JJV, Luime JJ. Factors associated with adherence to pharmaceutical treatment for rheumatoid arthritis patients: a systematic review. Semin Arthritis Rheum. 2013;43:18-28.
35. Romão VC, Vital EM, Fonseca JE, et al. Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis? Arthritis Res Ther. 2017;19:1-13. doi:10.1186/s13075-017-1445-3
36. Schaeverbeke T, Truchetet ME, Kostine M, et al. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology. 2016;55: 210-20.
37. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843-62. doi: 10.1038/nrd.2017.201
38. Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects. Drugs. 2017;77(5):521-46. doi: 10.1007/s40265-017-0701-9
39. Gadina M, Johnson C, Schwartz D, Bonelli M, Hasni S, et al. Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs. J Leukoc Biol. 2018;104(3):499-514. doi: 10.1002/JLB.5RI0218-084R
40. Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-77. doi: 10.1136/annrheumdis-2016-210715
41. Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1-26. doi: 10.1002/art.39480
42. Smolen JS, van der Heijde D, Machold KP, Aletaha D, Landewé R. Proposal for a new nomenclature of disease-modifying antirheumatic drugs. Ann Rheum Dis. 2014;73(1):3-5. doi: 10.1136/annrheumdis-2013-204317
43. Al-Salama ZT, Scott LJ. Baricitinib: A Review in Rheumatoid Arthritis. Drugs. 2018 May;78(7):761-72. doi: 10.1007/s40265-018-0908-4
44. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374:1243-52.
45. Genovese MC, Kremer JM, Kartman CE, Schlichting DE, Xie L, et al. Response to baricitinib based on prior biologic use in patients with refractory rheumatoid arthritis. Rheumatology (Oxford). 2018 May 1;57(5):900-8. doi: 10.1093/rheumatology/kex 489
46. Schiff M, Kelly S, Le Bars M, Genovese M. Efficacy of abatacept in RA patients with an inadequate response to anti-TNF therapy regardless of reason for failure, or type or number of prior anti-TNF therapy used. Ann Rheum Dis. 2008;67(Suppl 2):337.
47. Smolen JS, Kay J, Doyle MK, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor α inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009;374:210-21.
48. Kremer JM, Tony H, Tak PP, Luggen M, Mariette X, Hessey E. Efficacy of ritumixab in active RA patients with an inadequate response to one or more TNF inhibitors. Ann Rheum Dis. 2006;65(Suppl 2):326.
49. Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017 Apr;17(4):233-47. doi: 10.1038/nri.2017.1
50. Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol. 2018;30(2):207-14. doi: 10.1097/BOR
51. McInnes IB, Buckley CD, Isaacs JD. Cytokines in rheumatoid arthritis – shaping the immunological landscape. Nat Rev Rheumatol. 2016 Jan;12(1):63-8. doi:10.1038/ nrrheum.2015.171
52. Conrad C, Di Domizio J, Mylonas A, Belkhodja C, Demaria O, et al. TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis. Nat Commun. 2018;9(1):25. doi: 10.1038/s41467-017-02466-4
53. Toussirot É, Aubin F. Paradoxical reactions under TNF-α blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview. RMD Open. 2016 Jul 15;2(2):e000239. doi: 10.1136/ rmdopen-2015-000239
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Авторы
Е.Л. Насонов 1,2, А.М. Лила 1
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), кафедра ревматологии Института профессионального образования, Москва, Россия
________________________________________________
E.L. Nasonov 1,2, A.M. Lila 1
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), Department of Rheumatology of Professional Education Institute, Moscow, Russia