Preview

Научно-практическая ревматология

Расширенный поиск

Современная терапия интерстициальных пневмоний, ассоциированных с системной склеродермией

https://doi.org/10.47360/1995-4484-2020-520-531

Аннотация

В последние годы был достигнут значительный прогресс в лечении тяжелых проявлений системной склеродермии (ССД), таких как феномен Рейно, почечный криз, легочная артериальная гипертензия, что привело к повышению выживаемости и качества жизни. В то же время алгоритмы лечения интерстициального поражения легких при ССД пока не разработаны. В обзоре представлена характеристика эффективности препаратов с различными механизмами действия, включая иммуносупрессивные (циклофосфамид, микофенолата мофетил и др.) и высокодозную химиотерапию с последующей трансплантацией аутологичных гемопоэтических стволовых клеток. Отдельно рассмотрены новые препараты с антифиброзной активностью, в том числе недавно зарегистрированный в России для лечения интерстициальных заболеваний легких при ССД препарат нинтеданиб, перспективы применения генно-инженерных биологических препаратов (ГИБП) (ритуксимаба, тоцилизумаба и др.), и трансплантации легких.

Об авторе

Л. П. Ананьева
ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»
Россия

Ананьева Лидия Петровна, д.м.н., профессор, зав. лабораторией микроциркуляции и воспаления

115522, Москва, Каширское шоссе, 34а 



Список литературы

1. Manetti M., Matucci-Cerinic M. The new frontier in systemic sclerosis:from epigenetics to new treatments. Rheumatology. 2015;54:1757–1758. DOI: 10.1093/rheumatology/kev264.

2. Denton C.P., Khanna D. Systemic sclerosis. Lancet. 2017;390:1685–1699. DOI: 10.1016/S0140-6736(17)30933-9

3. Kowal-Bielecka O., Fransen J., Avouac J., et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76(8):1327–1133. DOI: 10.1136/annrheumdis-2016-209909. PMID: 27941129

4. Denton C.P., Hughes M., Gak N., et al. BSR and GHPR guideline for the treatment of systemic sclerosis. Rheumatology (Oxford). 2016;55:1906–1910. DOI: 10.1093/rheumatology/kew224.

5. Российские клинические рекомендации. Ревматология. Под ред. Е.Л. Насонова. М.: ГЭОТАР-Медиа, 2017:464.

6. Fernández-Codina A., Walker K.M., Pope J.E., Scleroderma Algorithm Group. Treatment algorithms for systemic sclerosis according to experts. Arthritis Rheumatol. 2018;70:1820–182. DOI: 10.1002/art.40560.

7. Elhai M., Meune C., Avouac J., et al. Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatol (Oxford). 2012;51:1017–1026. DOI: 10.1093/rheumatology/ker269.

8. Rubio-Rivas M., Royo C., Simeon C.P., et al. Mortality and survival in systemic sclerosis: systematic review and meta-analysis. Seminars in arthritis and rheumatism. 2014;44(2):208–219. DOI: 10.1016/j.semarthrit.2014.05.010.

9. Wijsenbeek M., Kreuter M., Amy Olson A., et al. Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management, Current Medical Research and Opinion. 2019;35:11:2015–2024. DOI: 10.1080/03007995.2019.1647040.

10. Iudici M., Fasano S., Iacono D., et al. Prevalence and factors associated with glucocorticoids (GC) use in systemic sclerosis (SSc): a systematic review and meta-analysis of cohort studies and registries. Clin Rheumatol. 2014;33(2):153–156. DOI: 10.1007/s10067-013-2422-0.

11. Adler S., Huscher D., Siegert E., et al. Systemic sclerosis associated interstitial lung disease-individualized immunosuppressive therapy and course of lung function: results of the EUSTAR group. Arthritis Res Ther. 2018;20(1):17. DOI: 10.1186/s13075-018-1517-z.

12. Hoyles R.K., Ellis R.W., Wellsbury J., et al. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum. 2006;54:3962–3970. DOI: 10.1002/art.22204.

13. Tashkin D.P., Elashoff R., Clements P.J., et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354:2655–2266. DOI: 10.1056/NEJMoa055120.

14. Tashkin D.P., Elashoff R., Clements P.J., et al. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med. 2007;176:1026–1034.

15. Roth M.D., Tseng C.H., Clements P.J., et al. Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease. Arthritis Rheum. 2011;63:2797–2808. DOI: 10.1002/art.30438.

16. Goldin J., Elashoff R., Kim H.J., et al. Treatment of scleroderma-interstitial lung disease with cyclophosphamide is associated with less progressive fibrosis on serial thoracic high-resolution CT scan than placebo: findings from the scleroderma lung study. Chest 2009;136:1333–1340. DOI: 10.1378/chest.09-0108.

17. Van Den Hombergh W.M.T., Simons S.O., Teesselink E., et al. Intravenous cyclophosphamide pulse therapy in interstitial lung disease associated with systemic sclerosis in a retrospective open-label study: influence of the extent of inflammation on pulmonary function. Clin Rheumatol. 2018;37:2715–2722. DOI: 10.1007/s10067-018-4171-6.

18. Volkmann E.R., Tashkin D.P., Sim M., et al. Cyclophosphamide for Systemic Sclerosisrelated Interstitial Lung Disease: A Comparison of Scleroderma Lung Study I and II. J Rheumatol. 2019. [Epub ahead of print]. DOI: 10.3899/jrheum.180441.

19. Dan D., Fischer R., Adler S., et al. Cyclophosphamide: as bad as its reputation? Long-term single centre experience of cyclophosphamide side effects in the treatment of systemic autoimmune diseases. Swiss Med Wkly. 2014;144:w140306. DOI: 10.4414/smw.2014.14030.

20. Omair M.A., Alahmadi A., Johnson S.R. Safety and effectiveness of mycophenolate in systemic sclerosis. A systematic review. PLoS One. 2015;10:e0124205. DOI: 10.1371/journal.pone.0124205.

21. Tashkin D.P., Roth M.D., Clements P.J., et al. Mycophenolate mofetil versus oral cyclophosphamide in sclerodermarelated interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016;4(9):708–719.

22. Pavlov-Dolijanovic S., Vujasinovic Stupar N., Zugic V., et al. Long-term effects of immunosuppressive therapy on lung function in scleroderma patients. Clin Rheumatol. 2018;37:30433050. DOI: 10.1007/s10067-018-4266-0.

23. Tyndall A., Gratwohl A.D. Adult stem cell transplantation in autoimmune disease. Curr Opin Hematol. 2009;16(4):285–291. DOI: 10.1097/MOH.0b013e32832aacb3.

24. Burt R.K., Milanetti F. Hematopoietic stem cell transplantation for systemic sclerosis:history and current status. Curr Opin Rheumatol. 2011;23:519–529. DOI: 10.1097/BOR.0b013e32834aa45f. PMID: 21857226

25. Van Laar J.M., Farge D., Sont J.K., et al. Autologous haemopoetic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014;311:2490–2498. DOI: 10.1001/jama.2014.6368.

26. Burt R.K., Shah S.J., Dill K., et al. Autologous non-myeloablativehemotopoetic stem-cell transplantation compared with pulse cyclophosphamide once per months for systemic sclerosis (ASSIST): an open label. Randomizedphase 2 trial. Lancet. 2011;378:498–506. DOI: 10.1016/S0140-6736(11)60982-3

27. Sullivan K.M., Goldmuntz E.A., Keyes-Elstein L., et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med. 2018;378:35–47.

28. Farge D., Burt R.K., Oliveire M.C., et al. Сardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party and collaborating partners. Bone Marrow Transplantation. 2017;52:1495–1503. DOI: 10.1038/bmt.2017.56.

29. Del Papa N., Pignataro F., Zaccara E., et al. Autologous hematopoietic stem cell transplantation for treatment of systemic sclerosis. Front Immunol. 2018;9:2390. DOI: 10.3389/fimmu.2018.02390.

30. Snowden J.A., Badoglio M., Labopin M., et al. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. BloodAdv. 2017;1:27422755. DOI: 10.1182/bloodadvances.2017010041.

31. Khanna D., Tashkin D.P., Denton C.P., et al. Ongoing clinical trials and treatment options for patients with systemic sclerosis-associated interstitial lung disease. Rheumatology. Epub ahead of print 8 June 2018. DOI: 10.1093/rheumatology/key151.

32. Giuggioli D., Lumetti F., Colaci M., et al. Rituximab in the treatment of patients with systemic sclerosis. Our experience and review of the literature. Autoimmun Rev. 2015;14:1072–1078. DOI: 10.1016/j.autrev.2015.07.008.

33. Daoussis D., Melissaropoulos K., Sakellaropoulos G., et al. A multicenter, open-label, comparative study of B-cell depletion therapy with Rituximab for systemic sclerosis-associated interstitial lung disease. SeminArthritisRheum. 2017;46(5):625–631. DOI: 10.1016/j.semarthrit.2016.10.003.

34. Jordan S., Distler J.H.W., Maurer B., et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2015;74:1188–1194. DOI: 10.1136/annrheumdis-2013-204522. PMID: 24442885

35. Sircar G., Goswami R.P., Sircar D., Ghosh A., Ghosh P. Intravenous Cyclophosphamide vs Rituximab for the Treatment of Early Diffuse Scleroderma Lung Disease: Open Label, Randomized, Controlled Trial Rheumatology (Oxford). 2018;57(12):2106–2113. DOI: 10.1093/rheumatology/key213.

36. Ананьева Л.П., Конева О.А., Десинова О.В. и др. Влияние ритуксимаба на проявления активности и легочную функцию у больных системной склеродермией: оценка после года наблюдения. Научно-практическая ревматология. 2019;57(3):265–273.

37. Saunders P., Tsipouri V., Keir G.J., et al. Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial. Trials. 2017;18:275. DOI: 10.1186/s13063-017-2016-2.

38. O’Reilly S., Cant R., Ciechomska M., van Laar J.M. Interleukin-6: a newtherapeutic target in systemic sclerosis? Clin Trans Immunology. 2013;2:e4. DOI: 10.1038/cti.2013.2.

39. Shima Y., Kuwahara Y., Murota H., et al. The skin of patients with systemic sclerosis softened during the treatment with antiIL-6 receptor antibody tocilizumab. Rheumatology. 2010;49:2408–2412. DOI: 10.1093/rheumatology/keq275.

40. Elhai M., Meunier M., Matucci-Cerinic M., et al. Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study. Ann Rheum Dis. 2013;72:1217–1220. DOI: 10.1136/annrheumdis-2012-202657.

41. Khanna D., Denton C.P., Jahreis A., et al. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial. Lancet. 2016;387:2630–264. DOI: 10.1016/S0140-6736(16)00232-4

42. Khanna D., Lin C.J.F., Kuwana М., et al. Efcacy and Safety of Tocilizumab for the treatment of systemic sclerosis: results from a phase 3 randomized controlled trial in Proceedings of the 2018 ACR/ARHP. Annual Meeting. 2018;898.

43. Khanna D., Denton C.P., Lin C.J.F., et al. Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis. 2018;77:212–220.

44. Zacay G., Levy Y. Outcomes of patients with systemic sclerosis treated with tocilizumab: Case series and review of the literature. Best Practice & Research Clinical Rheumatology. 2018;32(4):563–571. DOI: 10.1016/j.berh.2019.01.011.

45. Shima Y. The benefits and prospects of interleukin-6 inhibitor on systemic sclerosis. MODERN RHEUMATOLOGY. 2019;29(2):294–301. DOI: 10.1080/14397595.2018.1559909.

46. Fuschiotti P., Medsger T.A., Jr, Morel P.A. Effector CD8þT cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosis. Arthritis Rheum. 2009;60(4):1119–1128. DOI: 10.1002/art.24432.

47. Khanna D., Spino K., Sindhu Johnson S., et al. Abatacept in Early Diffuse Cutaneous Systemic Sclerosis: Results of a Phase II Investigator-Initiated, Multicenter, Double-Blind, Randomized. Placebo-Controlled Trial Arthritis & Rheumatology. 2020;72(1):125–136.

48. Sierra-Sepúlveda A., Esquinca-González A., BenavidesSuárez S.A., et al. Systemic Sclerosis Pathogenesis and Emerging Therapies. Fibroblast BioMed Research International. 2019. 15 p. DOI: 10.1155/2019/4569826.

49. Allanore Y., Distler О., Jagerschmidt А., et al. Lysophosphatidic Acid Receptor 1 Antagonist SAR100842 for Patients With Diffuse Cutaneous Systemic Sclerosis. Arthritis & Rheumatology. 2018;70(10):1634–1643. DOI: 10.1002/art.40547.

50. Cottin and Brown Interstitial lung disease associated with systemic sclerosis (SSc-ILD). Respiratory Research. 2019;20:13. DOI: 10.1186/s12931-019-0980-7.

51. Spiera R., Hummers L. Chung L. Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with systemic sclerosis. Arthritis Rheumatol. 2020. DOI: 10.1002/art.41294.

52. Misra D.P., Ahmed S., Agarwal V. Is biological therapy in systemic sclerosis the answer? RheumatolInt. 2020;40:679–694. DOI: 10.1007/s00296-020-04515-6.

53. Wollin L., Maillet I., Quesniaux V., et al. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitornintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther. 2014;349:209–222. DOI: 10.1124/jpet.113.208223.

54. Wollin L., Wex E., Pautsch A., et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45:1434–1445. DOI: 10.1183/09031936.00174914.

55. Tandon K., Herrmann F.E., Ayaub E., et al. Nintedanib attenuates the polarization of profibrotic macrophages through the inhibition of tyrosine phosphorylation on CSF1 receptor. Am J Respir Crit Care Med. 2017;195:A2397.

56. Huang J., Beyer C., Palumbo-Zerr K., et al. Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical models of systemic sclerosis. Ann Rheum Dis. 2016;75:883–890. DOI: 10.1136/annrheumdis-2014-207109.

57. Huang J., Maier C., Zhang Y., et al. Nintedanib inhibits macrophage activation and ameliorates vascular and fibrotic manifestations in the Fra2 mouse model of systemic sclerosis. Ann Rheum Dis. 2017;76:1941–1948. DOI: 10.1136/annrheumdis-2016-210823. PMID: 28814429

58. Wollin L., Ostermann A., Williams C. Nintedanib inhibits pro-fibrotic mediators from T cells with relevance to connective tissue disease-associated interstitial lung disease. Eur Respir J. 2017;50(Suppl. 61):PA903. DOI: 10.1183/1393003.congress-2017.PA903

59. Ackermann M., Kim Y.O., Wagner W.L., et al. Effects of nintedanib on the microvascular architecture in a lung f ibrosis model. Angiogenesis. 2017;20:359–372. DOI: 10.1007/s10456-017-9543-z. PMID: 28283856

60. Richeldi L., Du Bois R.M., Raghu G., et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–2082. DOI: 10.1056/NEJMoa1402584.

61. Lancaster L., Crestani B., Hernandez P., et al. Safety and survival data in patients with idiopathic pulmonary fibrosis treated with nintedanib: pooled data from six clinical trials. BMJ Open Respir Res. 2019;6:e000397. DOI: 10.1136/bmjresp-2018-000397.

62. Wollin L., Distler J.H.W., Denton C.P., et al. Rationale for the evaluation of nintedanib as a treatment for systemic sclerosis-associated interstitial lung disease. J Scleroderma Relat Disord. 2019. Epub ahead of print. DOI: 10.1177/2397198319841842

63. Richeldi L., Varone F., Bergna M., et al. Pharmacological management of progressive-fibrosing interstitial lung diseases: a review of the current evidence. Eur Respir Rev. 2018;27(150):180074. 2018. DOI: 10.1183/16000617.0074-2018

64. Wells A.U., Brown K.K., Flaherty K.R., et al. What’s in a name? That which we call IPF, by any other name would act the same. Eur Respir J. 2018;51:1800692. DOI: 10.1183/13993003.00692-2018.

65. Cottin V., Wollin L., Fischer A., Quaresma M., Stowasser S., Harari S. Fibrosing interstitial lung diseases: knowns and unknowns. Eur Respir Rev. 2019;28(151):180100. Published 2019. DOI:10.1183/16000617.0100-2018.

66. Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, Raghu G, Sauter W, Girard M, Alves M, ClerismeBeaty E, Stowasser S, Tetzlaff K, Kuwana M, Maher TM; SENSCIS Trial Investigators. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019;380(26):2518-2528. doi: 10.1056/NEJMoa1903076

67. Fischer A., Distler J. Progressive fibrosing interstitial lung disease associated with systemic autoimmune diseases. Clin Rheumatol. 2019;38(10):2673–2681. DOI: 10.1007/s10067-019-04720-0.

68. Hoffmann-Vold А.-M., Weigt S.S., Saggar R., et al. Endotypephenotyping may predict a treatment response in progressive fibrosing interstitial lung disease. E Bio Medicine 2020. DOI: 10.1016/j.ebiom.2019.10.050

69. Flaherty K.R., Wells A.U., Cottin V.D., et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019;381(18):1718–1727. DOI: 10.1056/NEJMoa1908681.

70. Clinical Trials.gov and EMD Serono Inc: National Library of Medicine (US), Abituzumab in SSc-ILD. Identifer NCT02745145. 2018. https://clinicaltrials.gov/ct2/show/NCT02745145

71. Clinical Trials.gov and Matucci (MD): National Library of Medicine (US), Efcacy and Safety Study of p144 to Treat Skin Fibrosis in Systemic Sclerosis. Identifer NCT00574613. 2007. clinicaltrials.gov/ct2/show/NCT00574613

72. Rice L.M., Padilla С.М., McLaughlin S.R., et al. Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients. Te J Clin Invest. 2015;125(7):27952807. DOI: 10.1172/JCI77958.

73. Khanna D. An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Sclerodermaassociated Interstitial Lung Disease: the LOTUSS Trial. J. Rheumatol. 2016;43(9):1672–1679. DOI: 10.3899/jrheum.151322.

74. Weill D., Benden C., Corris P.A., Dark J.H., Davis R.D., Keshavjee S., et al. A consensus document for the selection of lung transplant candidates: 2014-an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2015;34:1–15. DOI: 10.1016/j.healun.2014.06.014.

75. Bernstein E.J., Peterson E.R., Sell J.L., et al. Survival of adults with systemic sclerosis following lung transplantation: a nationwide cohort study. Arthritis Rheum. 2015;67(5):1314–1322. DOI: 10.1002/art.39021.

76. Khan I.Y., Singer L.G., de Perrot M., et al. Survival after lung transplantation in systemic sclerosis. A systematic review. Respir Med. 2013;107(12):2081–2087. DOI: 10.1016/j.rmed.2013.09.015.

77. Crespo M.M., Bermudez C.A., Dew M.A., et al. Lung Transplant in Patients with Scleroderma Compared with Pulmonary Fibrosis. Short- and Long-Term Outcomes. Ann Am Thorac Soc. 2016;13(6):784–792. DOI: 10.1513/AnnalsATS.201503-177OC.

78. Miele C.H., Schwab K., Saggar R., et al. Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience. Ann Am Thorac Soc. 2016;13(6):793–802.

79. Fernández-Codinaa А., Berastegui С., Pinal-Fernández I., et al. Lung transplantation in systemic sclerosis: A single center cohort study Joint Bone Spine. 2018;85(1):79–84. DOI: 10.1016/j.jbspin.2017.03.012.

80. Nihtyanova S.I., Tang E.C., Coghlan J.G., Wells A.U., Black С.М., Denton С.Р. Improved survival in systemic sclerosis is associated with better ascertainment of internal organ disease: A retrospective cohort study. QJM. 2009;103(2):109–115. DOI: 10.1093/qjmed/hcp174.

81. Khanna D., Distler J.H.W., Sandner P., et al. Emerging strategies for treatment of systemic sclerosis. J Scleroderma Relat Disord. 2016;1:186–193. DOI: 10.5301/jsrd.5000207


Рецензия

Для цитирования:


Ананьева Л.П. Современная терапия интерстициальных пневмоний, ассоциированных с системной склеродермией. Научно-практическая ревматология. 2020;58(5):520-531. https://doi.org/10.47360/1995-4484-2020-520-531

For citation:


Ananieva L.P. Current therapy of interstitial pneumonia associated with systemic scleroderma. Rheumatology Science and Practice. 2020;58(5):520-531. (In Russ.) https://doi.org/10.47360/1995-4484-2020-520-531

Просмотров: 1131


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


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