Отмена ингаляционных глюкокортикостероидов у пациентов с хронической обструктивной болезнью легких

Роль ингаляционных глюкокортикостероидов (иГКС) в терапии пациентов с хронической обструктивной болезнью легких (ХОБЛ) в со - временных клинических рекомендациях ограничена. Хотя оптимальное соотношение польза / риск и может быть достигнуто в специфических популяциях этих больных, однако в реальной клинической практике врачи зачастую не следуют клиническим рекомендациям и многие пациенты с ХОБЛ получают иГКС необоснованно. Наряду с отсутствием эффективности применение иГКС может быть связано с возможными рисками, которые могут превосходить потенциальную пользу от применения препаратов этого класса у больных ХОБЛ. Эти данные диктуют необходимость разработки простого и удобного алгоритма для врачей по отмене иГКС у пациентов, которым применение препаратов этого класса не показано. В настоящей статье анализируются исследования, посвященные эффективности и безопасности иГКС, а также доступные данные по отмене иГКС у пациентов с ХОБЛ. На основании актуальных данных международной группой экспертов разработан простой и удобный алгоритм по отмене иГКС у больных ХОБЛ.

хроническая обструктивная болезнь легких, ингаляционные препараты, ингаляционные глюкокортикостероиды, отмена ингаляционных глюкокортикостероидов, бронходилататоры длительного действия, алгоритм отмены ингаляционных глюкокортикостероидов

1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Prevention, Diagnosis and Management of COPD. 2019 GOLD Reports. Available at: https://goldcopd.org/gold-reports/ (Accessed: December 11, 2018).

2. Barnes P.J. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin. Chest Med. 2014; 35 (1): 71–86. DOI: 10.1016/j.ccm.2013.10.004.

3. Cataldo D., Derom E., Liistro G. et al. Overuse of inhaled corticosteroids in COPD: five questions for withdrawal in daily practice. Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13: 2089–2099. DOI: 10.2147/COPD.S164259.

4. Nannini L.J., Lasserson T.J., Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2012; (9): CD006829. DOI: 10.1002/14651858.CD006829.pub2.

5. Celli B.R., Thomas N.E., Anderson J.A. et al. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am. J. Respir. Crit. Care Med. 2008; 178 (4): 332–338. DOI: 10.1164/rccm.200712-1869OC.

6. Gershon A.S., Campitelli M.A., Croxford R. et al. Combination long-acting β-agonists and inhaled corticosteroids compared with long-acting β-agonists alone in older adults with chronic obstructive pulmonary disease. JAMA. 2014; 312 (11): 1114–1121. DOI: 10.1001/jama.2014.11432.

7. Lee J.H., Lee Y.K., Kim E.K. et al. Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype. Respir. Med. 2010; 104 (4): 542–549. DOI: 10.1016/j.rmed.2009.10.024.

8. Agusti A., Bel E., Thomas M. et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur. Respir. J. 2016; 47 (2): 410–419. DOI: 10.1183/13993003.01359-2015.

9. Dicker A.J., Crichton M.L., Pumphrey E.G. et al. Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 2018; 141 (1): 117–127. DOI: 10.1016/j.jaci.2017.04.022.

10. Contoli M., Pauletti A., Rossi M.R. et al. Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD. Eur. Respir. J. 2017; 50 (4): pii 1700451. DOI: 10.1183/13993003.00451-2017.

11. Chalmers J.D. POINT: Should an attempt be made to withdraw inhaled corticosteroids in all patients with stable GOLD 3 (30% ≤ FEV1 < 50% predicted) COPD? Yes. Chest. 2018; 153 (4): 778–782. DOI: 10.1016/j.chest.2018.01.029.

12. Yawn B.P., Li Y., Tian H. et al. Inhaled corticosteroid use in patients with chronic obstructive pulmonary disease and the risk of pneumonia: a retrospective claims data analysis. Int. J. Chron. Obstruct. Pulmon. Dis. 2013; 8: 295–304. DOI: 10.2147/COPD.S42366.

13. Arkhipov V., Arkhipova D., Miravitlles M. et al. Characteristics of COPD patients according to GOLD classification and clinical phenotypes in the Russian Federation: the SUPPORT trial. Int. J. Chron. Obstruct. Pulmon. Dis. 2017; 12: 3255–3262. DOI: 10.2147/COPD.S142997.

14. Price D., Yawn B., Brusselle G., Rossi A. Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD. Prim. Care Respir. J. 2013; 22 (1): 92–100. DOI: 10.4104/pcrj.2012.00092.

15. Pauwels R.A., Lofdahl C.G., Laitinen L.A. et al. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N. Engl. J. Med. 1999; 340 (25): 1948–1953. DOI: 10.1056/NEJM199906243402503.

16. Burge P.S., Calverley P.M, Jones P.W. et al. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. Br. Med. J. 2000; 320 (7245): 1297–1303. DOI: 10.1136/bmj.320.7245.1297.

17. Jones P.W., Willits L.R., Burge P.S., Calverley P.M. Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations. Eur. Respir. J. 2003; 21 (1): 68–73. DOI: 10.1183/09031936.03.00013303.

18. Zervas E., Samitas K., Gaga M. et al. Inhaled corticosteroids in COPD: pros and cons. Curr. Drug Targets. 2013; 14 (2): 192–224. DOI: 10.2174/1389450111314020006.

19. Cheng S.L., Su K.C., Wang H.C. et al. Chronic obstructive pulmonary disease treated with inhaled medium- or highdose corticosteroids: a prospective and randomized study focusing on clinical efficacy and the risk of pneumonia. Drug Des. Devel. Ther. 2014; 8: 601–607. DOI: 10.2147/DDDT.S63100.

20. Calverley P.M., Anderson J.A., Celli B. et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N. Engl. J. Med. 2007; 356 (8): 775–789. DOI: 10.1056/NEJMoa063070.

21. Vestbo J., Anderson J.A., Brook R.D. et al. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet. 2016; 387 (10030): 1817–1826. DOI: 10.1016/S0140-6736(16)30069-1.

22. Rossi A., van der Molen T., del Olmo R. et al. INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD. Eur. Respir. J. 2014; 44 (6): 1548–1556. DOI: 10.1183/09031936.00126814.

23. Szafranski W., Cukier A., Ramirez A. et al. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease. Eur. Respir. J. 2003; 21 (1): 74–81. DOI: 10.1183/09031936.03.00031402.

24. Calverley P.M., Boonsawat W., Cseke Z. et al. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur. Respir. J. 2003; 22 (6): 912–919. DOI: 10.1183/09031936.03.00027003.

25. Rodrigo G.J., Castro-Rodriguez J.A., Plaza V. Safety and efficacy of combined long-acting beta-agonists and inhaled corticosteroids vs long-acting beta-agonists monotherapy for stable COPD: a systematic review. Chest. 2009; 136 (4): 1029–1038. DOI: 10.1378/chest.09-0821.

26. Wedzicha J.A., Calverley P.M., Seemungal T.A. et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am. J. Respir. Crit. Care Med. 2008; 177 (1): 19–26. DOI: 10.1164/rccm.200707-973OC.

27. Barnes P.J. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 2013; 131 (3): 636–645. DOI: 10.1016/j.jaci.2012.12.1564.

28. Pascoe S., Locantore N., Dransfield M.T. et al. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir. Med. 2015; 3 (6): 435–442. DOI: 10.1016/S2213-2600(15)00106-X.

29. Siddiqui S.H., Guasconi A., Vestbo J. et al. Blood eosinophils: a biomarker of response to extrafine beclomethasone/formoterol in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2015; 192 (4): 523–525. DOI: 10.1164/rccm.201502-0235LE.

30. Wedzicha J.A., Banerji D., Chapman K.R. et al. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N. Engl. J. Med. 2016; 374 (23): 2222–2234. DOI: 10.1056/NEJMoa1516385.

31. Roche N., Chapman K.R., Vogelmeier C.F. et al. Blood eosinophils and response to maintenance chronic obstructive pulmonary disease treatment. data from the FLAME trial. Am. J. Respir. Crit. Care Med. 2017; 195 (9): 1189–1197. DOI: 10.1164/rccm.201701-0193OC.

32. Ernst P., Saad N., Suissa S. Inhaled corticosteroids in COPD: the clinical evidence. Eur. Respir. J. 2015; 45 (2): 525–537. DOI: 10.1183/09031936.00128914.

33. Kew K.M., Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2014; (3): CD010115. DOI: 10.1002/14651858.CD010115.pub2.

34. Brode S.K., Campitelli M.A., Kwong J.C. et al. The risk of mycobacterial infections associated with inhaled corticosteroid use. Eur. Respir. J. 2017; 50 (3): pii 1700037. DOI: 10.1183/13993003.00037-2017.

35. Loke Y.K., Cavallazzi R., Singh S. Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax. 2011; 66 (8): 699–708. DOI: 10. 1136/thx.2011.160028.

36. Suissa S., Kezouh A., Ernst P. Inhaled corticosteroids and the risks of diabetes onset and progression. Am. J. Med. 2010; 123 (11): 1001–1006. DOI: 10.1016/j.amjmed.2010.06.019.

37. Horita N., Goto A., Shibata Y. et al. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD). Cochrane Database Syst. Rev. 2017; (2): CD012066. DOI: 10.1002/14651858.CD012066.pub2.

38. Yang I.A., Clarke M.S., Sim E.H., Fong K.M. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2012; (7): CD002991. DOI: 10.1002/14651858.CD002991.pub3.

39. Weatherall M., Clay J., James K. et al. Dose-response relationship of inhaled corticosteroids and cataracts: a systematic review and meta-analysis. Respirology. 2009; 14 (7): 983–990. DOI: 10.1111/j.1440-1843.2009.01589.x.

40. Uboweja A., Malhotra S., Pandhi P. Effect of inhaled corticosteroids on risk of development of cataract: a meta-analysis. Fundam. Clin. Pharmacol. 2006; 20 (3): 305–309. DOI: 10.1111/j.1472-8206.2006.00397.x.

41. Huang K.W., Kuan Y.C., Chi N.F. et al. Chronic obstructive pulmonary disease is associated with increased recurrent peptic ulcer bleeding risk. Eur. J. Intern. Med. 2017; 37: 75–82. DOI: 10.1016/j.ejim.2016.09.020.

42. Rossi A.P., Zanardi E., Zamboni M., Rossi A. Optimizing treatment of elderly COPD patients: what role for inhaled corticosteroids? Drugs Aging. 2015; 32 (9): 679–687. DOI: 10.1007/s40266-015-0291-8.

43. van der Valk P., Monninkhof E., van der Palen J. et al. Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study. Am. J. Respir. Crit. Care Med. 2002; 166 (10): 1358–1363. DOI: 10.1164/rccm.200206-512OC.

44. Choudhury A.B., Dawson C.M., Kilvington H.E. et al. Withdrawal of inhaled corticosteroids in people with COPD in primary care: a randomised controlled trial. Respir. Res. 2007; 8: 93. DOI: 10.1186/1465-9921-8-93.

45. Wouters E.F., Postma D.S., Fokkens B. et al. Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: a randomised controlled trial. Thorax. 2005; 60 (6): 480–487. DOI: 10.1136/thx.2004.034280.

46. Rossi A., Guerriero M., Corrado A. Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO). Respir. Res. 2014; 15: 77. DOI: 10.1186/1465-9921-15-77.

47. Vogelmeier C., Worth H., Buhl R. et al. "Real-life" inhaled corticosteroid withdrawal in COPD: a subgroup analysis of DACCORD. Int. J. Chron. Obstruct. Pulmon. Dis. 2017; 12: 487–494. DOI: 10.2147/COPD.S125616.

48. Magnussen H., Disse B., Rodriguez-Roisin R. et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N. Engl. J. Med. 2014; 371 (14): 1285–1294. DOI: 10.1056/NEJMoa1407154.

49. Magnussen H., Tetzlaff K., Bateman E.D. et al. Lung function changes over time following withdrawal of inhaled corticosteroids in patients with severe COPD. Eur. Respir. J. 2016; 47 (2): 651–654. DOI: 10.1183/13993003.01644-2015.

50. Watz H., Tetzlaff K., Wouters E.F. et al. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial. Lancet Respir. Med. 2016; 4 (5): 390–398. DOI: 10.1016/S2213-2600(16)00100-4.

51. Vogelmeier C.F., Gaga M., Aalamian-Mattheis M. et al. Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial. Respir. Res. 2017; 18 (1): 140. DOI: 10.1186/s12931-017-0622-x.

52. Chapman K.R., Hurst J.R., Frent S.M. et al. Long-term triple therapy de-escalation to indacaterol/glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET): a randomized, double-blind, triple-dummy clinical trial. Am. J. Respir. Crit. Care Med. 2018; 198 (3): 329–339. DOI: 10.1164/rccm.201803-0405OC.

53. Frith P.A., Ashmawi S., Krishnamurthy S. et al. Efficacy and safety of the direct switch to indacaterol/glycopyrronium from salmeterol/fluticasone in non-frequently exacerbating COPD patients: The FLASH randomized controlled trial. Respirology. 2018; 23 (12): 1152–1159. DOI: 10.1111/resp.13374.

54. Suissa S., Coulombe J., Ernst P. Discontinuation of inhaled corticosteroids in COPD and the risk reduction of pneumonia. Chest. 2015; 148 (5): 1177–1183. DOI: 10.1378/chest.15-0627.

55. Jarad N.A., Wedzicha J.A., Burge P.S., Calverley P.M. An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease. Respir. Med. 1999; 93 (3): 161–166. DOI: 10.1016/S0954-6111(99)90001-X.

56. Sulaiman I., Cushen B., Greene G. et al. Objective assessment of adherence to inhalers by patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2017; 195 (10): 1333–1343. DOI: 10.1164/rccm.201604-0733OC.

57. Kardos P., Vogelmeier C., Worth H. et al. A two-year evaluation of the 'real life' impact of COPD on patients in Germany: The DACCORD observational study. Respir. Med. 2017; 124: 57–64. DOI: 10.1016/j.rmed.2017.02.007. 58. Harlander M., Barrecheguren M., Turel M., Miravitlles M. Should patients switched from D to B in the GOLD 2017 classification be discontinued from inhaled corticosteroids? COPD. 2017; 14 (5): 465–468. DOI: 10.1080/15412555.2017.1342233.

58. Авдеев С.Н., Айсанов З.Р., Белевский А.С. и др. Перспективы фармакотерапии хронической обструктивной болезни легких: возможности комбинированных бронходилататоров и место ингаляционных глюкокортикостероидов. Заключение Совета экспертов. Пуль монология. 2016; 26 (1): 65–72. DOI: 10.18093/0869-0189- 2016-26-1-65-72.

59. Авдеев С.Н., Айсанов З.Р., Белевский А.С. и др. Новые возможности в профилактике обострений хронической обструктивной болезни легких. Заключение группы специалистов Российского респираторного общества. Пульмонология. 2017; 27 (1): 108–113. DOI: 10. 18093/0869-0189-2017-27-1-108-113.

60. Авдеев С.Н., Белевский А.С., Айсанов З.Р. и др. Возможности ингаляционной терапии по предупреждению обострений хронической обструктивной болезни легких. Заключение Совета экспертов Российского респираторного общества. Пульмонология. 2018; 28 (3): 368–380. DOI: 10.18093/0869-0189-2018-28-3-368-380.

61. Crim C., Dransfield M.T., Bourbeau J. et al. Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD. Ann. Am. Thorac. Soc. 2015; 12 (1): 27–34. DOI: 10.1513/AnnalsATS.201409-413OC.

62. Matkovic Z., Miravitlles M. Chronic bronchial infection in COPD. Is there an infective phenotype? Respir. Med. 2013; 107 (1): 10–22. DOI: 10.1016/j.rmed.2012.10.024.

63. Miravitlles M., Anzueto A. Antibiotic prophylaxis in COPD: why, when, and for whom? Pulm. Pharmacol Ther. 2015; 32: 119–123. DOI: 10.1016/j.pupt.2014.05.002.

64. Izquierdo J.L., Cosio B.G. The dose of inhaled corticosteroids in patients with COPD: when less is better. Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13: 3539–3547. DOI: 10.2147/COPD.S175047.

65. Suissa S., Patenaude V., Lapi F., Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013; 68 (11): 1029–1036. DOI: 10.1136/thoraxjnl-2012-202872.

66. Lipworth B., Kuo C.R., Jabbal S. Current appraisal of single inhaler triple therapy in COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13: 3003–3009. DOI: 10.2147/COPD.S177333.

67. Janson C., Stratelis G., Miller-Larsson A. et al. Scientific rationale for the possible inhaled corticosteroid intraclass difference in the risk of pneumonia in COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2017; 12: 3055–3064. DOI: 10.2147/COPD.S143656.