Интерлейкин 5 – новая мишень для терапии эозинофильного гранулематоза с полиангиитом
Аннотация
Интерлейкин 5 (ИЛ5) участвует в созревании и активации эозинофилов, его продукция повышена при эозинофильном гранулематозе с полиангиитом (ЭГПА). Эта редкая форма системных васкулитов (СВ) характеризуется периферической эозинофилией и поражением многих органов и систем. Внедрение в клиническую практику глюкокортикоидов (ГК) и цитостатиков значительно улучшило прогноз ЭГПА, но их применение сопряжено со значительными неблагоприятными реакциями и может быть недостаточно эффективно. При использовании стандартных схем лечения не всегда удается добиться ремиссии, сохраняется высокая частота рецидивов ЭГПА. Меполизумаб является антагонистом ИЛ5 и перспективным средством для лечения больных ЭГПА. В представленном обзоре литературы рассматриваются аргументы в пользу применения меполизумаба при ЭГПА и обсуждаются вопросы его эффективности и безопасности. Накопленные в настоящее время данные свидетельствуют об эффективности и безопасности меполизумаба у пациентов с ЭГПА, что было продемонстрировано в регистрационном двойном слепом рандомизированном плацебоконтролируемом исследовании MIRRA. Лечение антагонистом ИЛ5 позволяет контролировать как симптомы бронхиальной астмы, так и проявления СВ, повышает вероятность достижения ремиссии ЭГПА, может способствовать снижению риска рецидива, дает возможность минимизировать дозу ГК.
Об авторах
Т. В. Бекетова
ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»
Россия
Россия
Татьяна Валентиновна Бекетова
115522, Москва, Каширское шоссе, 34А
Е. В. Арсеньев
ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»
Россия
115522, Москва, Каширское шоссе, 34А
Россия
115522, Москва, Каширское шоссе, 34А
Список литературы
1. Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or Placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017 May 18;376(20):1921-32. doi: 10.1056/NEJMoa1702079
2. Comarmond C, Pagnoux C, Khellaf M, et al; French Vasculitis Study Group. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum. 2013 Jan;65(1):270-81. doi: 10.1002/art.37721
3. Vaglio A, Buzio C, Zwerina J. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): state of the art. Allergy. 2013 Mar;68(3):261-73. doi: 10.1111/all.12088
4. Robson J, Doll H, Suppiah R, et al. Glucocorticoid treatment and damage in the anti-neutrophil cytoplasm antibody-associated vasculitides: long-term data from the European Vasculitis Study Group trials. Rheumatology (Oxford). 2015 Mar;54(3):471-81. doi: 10.1093/rheumatology/keu366
5. Doubelt I, Pulenzas N, Carette S, Pagnoux C; Canadian Vasculitis Network (CanVasc). Efficacy of conventional immunosuppressants in relapsing or refractory eosinophilic granulomatosis with polyangiitis: evidence from a Canadian single-centre cohort. Clin Exp Rheumatol. 2020 Mar 11 [Epub ahead of print]. PubMed PMID: 32167871.
6. McGregor JG, Hogan SL, Hu Y, et al. Glucocorticoids and relapse and infection rates in anti-neutrophil cytoplasmic antibody disease. Clin J Am Soc Nephrol. 2012 Feb;7(2):240-7. doi: 10.2215/CJN.05610611
7. Pagnoux C, Quеmеneur T, Ninet J, et al. Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, openlabel, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy. Arthritis Rheum. 2015;67(4):1117-27. doi: 10.1002/art.39011
8. Jakiela B, Szczeklik W, Plutecka H, et al. Increased production of IL-5 and dominant Th2-type response in airways of ChurgStrauss syndrome patients. Rheumatology (Oxford). 2012 Oct;51(10):1887-93. doi: 10.1093/rheumatology/kes171
9. Free ME, Bunch DO, McGregor JA, et al. Patients with antineutrophil cytoplasmic antibody-associated vasculitis have defective Treg cell function exacerbated by the presence of a suppressionresistant effector cell population. Arthritis Rheum. 2013 Jul;65(7):1922-33. doi: 10.1002/art.37959
10. Sinico RA, Di Toma L, Maggiore U, et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in ChurgStrauss syndrome. Arthritis Rheum. 2005 Sep;52(9):2926-35. doi: 10.1002/art.21250
11. Sable-Fourtassou R, Cohen P, Mahr A, et al; French Vasculitis Study Group. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med. 2005 Nov 1;143(9):632- 8. doi: 10.7326/0003-4819-143-9-200511010-00006
12. Vaglio A, Strehl JD, Manger B, et al. IgG4 immune response in Churg-Strauss syndrome. Ann Rheum Dis. 2012 Mar;71(3):390-3. doi: 10.1136/ard.2011.155382
13. Paul CC, Keller JR, Armpriester JM, Baumann MA. Epstein-Barr virus transformed B lymphocytes produce interleukin-5. Blood. 1990;75:1400-3. doi: 10.1182/blood.V75.7.1400.1400
14. Takatsu K. Interleukin-5 and IL-5 receptor in health and diseases. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87(8):463-85. doi: 10.2183/pjab.87.463
15. Насонов ЕЛ, Бекетова ТВ, Ананьева ЛП и др. Перспективы анти-В-клеточной терапии при иммуновоспалительных ревматических заболеваниях. Научно-практическая ревматология. 2019;57(Прил. 1):3-40. doi: 10.14412/1995-4484-2019-3-40 [Nasonov EL, Beketova TV, Ananyeva LP, et al. Prospects for anti-B-cell therapy in immuno-inflammatory rheumatic diseases. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2019;57(Suppl 1):3-40. doi: 10.14412/1995-4484- 2019-3-40 (In Russ.)].
16. Khoury P, Grayson PC, Klion AD. Eosinophils in vasculitis: characteristics and roles in pathogenesis. Nat Rev Rheumatol. 2014 Aug;10(8):474-83. doi: 10.1038/nrrheum.2014.98
17. Varricchi G, Bagnasco D, Borriello F, et al. Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs. Curr Opin Allergy Clin Immunol. 2016 Apr;16(2):186-200. doi: 10.1097/ACI.0000000000000251
18. Mü schen M, Warskulat U, Perniok A, et al. Involvement of soluble CD95 in Churg-Strauss syndrome. Am J Pathol. 1999 Sep;155(3):915-25. doi: 10.1016/S0002-9440(10)65191-7
19. Sano K, Kobayashi M, Sakaguchi N, et al. A rat model of hypereosinophilic syndrome. Pathol Int. 2001;51:82-8. doi: 10.1046/j.1440-1827.2001.01175.x
20. Patella V, de Crescenzo G, Marino I, et al. Eosinophil granule proteins are selective activators of human heart mast cells. Int Arch Allergy Immunol. 1997;113:200-2. doi: 10.1159/000237546
21. Lampinen M, Carlson M, Hakansson LD, Venge P. Cytokine-regulated accumulation of eosinophils in inflammatory disease. Allergy. 2004 Aug;59(8):793-805. doi: 10.1111/j.1398-9995.2004.00469.x
22. Zhu J, Yamane H, Cote-Sierra J, et al. GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res. 2006 Jan;16(1):3-10. doi: 10.1038/sj.cr.7310002
23. Kahn J-E, Grandpeix-Guyodo C, Marroun I, et al. Sustained response to mepolizumab in refractory Churg-Strauss syndrome. J Allergy Clin Immunol. 2010 Jan;125(1):267-70. doi: 10.1016/j.jaci.2009.10.014
24. Shiota Y, Matsumoto H, Kanehisa Y, et al. Serum interleukin-5 levels in a case with allergic granulomatous angiitis. Intern Med. 1997;36:709-11. doi: 10.2169/internalmedicine.36.709
25. Stein ML, Villanueva JM, Buckmeier BK, et al. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol. 2008 Jun;121(6):1473-83, 1483.e1-4. doi: 10.1016/j.jaci.2008.02.033
26. Owen WF, Rothenberg ME, Petersen J, et al. Interleukin 5 and phenotypically altered eosinophils in the blood of patients with the idiopathic hypereosinophilic syndrome. J Exp Med. 1989;170:343-8. doi: 10.1084/jem.170.1.343
27. Roufosse F, Schandene L, Sibille C, et al. Clonal Th2 lymphocytes in patients with the idiopathic hypereosinophilic syndrome. Br J Haematol. 2000;109:540-8. doi: 10.1046/j.1365-2141.2000.02097.x
28. Humbert M, Corrigan CJ, Kimmitt P, et al. Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. Am J Respir Crit Care Med. 1997;156:704-8. doi: 10.1164/ajrccm.156.3.9610033
29. Mortuaire G, Gengler I, Vandenhende-Szymanski C, et al. Immune profile modulation of blood and mucosal eosinophils in nasal polyposis with concomitant asthma. Ann Allergy Asthma Immunol. 2015 Apr;114(4):299-307.e2. doi: 10.1016/j.anai.2015.01.012
30. Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol. 2004;113:11-28. doi: 10.1016/j.jaci.2003.10.047
31. Straumann A, Bauer M, Fischer B, et al. Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic inflammatory response. J Allergy Clin Immunol. 2001;108:954-61. doi: 10.1067/mai.2001.119917
32. Buckingham JC. Glucocorticoids: exаmplеs of multi-tasking. Br J Pharmacol. 2006 Jan;147 Suppl 1:S258-68. doi: 10.1038/sj.bjp.0706456
33. Giembycz MA, Lindsay MA. Pharmacology of the eosinophil. Pharmacol Rev. 1999;51:213-340.
34. Bao S, McClure SJ, Emery DL, Husband AJ. Interleukin-5 mRNA expressed by eosinophils and gamma/delta T cells in parasite-immune sheep. Eur J Immunol. 1996;26:552-6. doi: 10.1002/eji.1830260308
35. Yoshimura-Uchiyama C, Yamaguchi M, Nagase H, et al. Changing expression of IL-3 and IL-5 receptors in cultured human eosinophils. Biochem Biophys Res Commun. 2003 Sep 12;309(1):26-31. doi: 10.1016/S0006-291X(03)01526-2
36. Molfino NA, Gossage D, Kolbeck R, et al. Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin Exp Allergy. 2012 May;42(5):712-37. doi: 10.1111/j.1365-2222.2011.03854.x
37. King B, Lee AI, Choi J. Treatment of hypereosinophilic syndrome with cutaneous involvement with the JAK inhibitors Tofacitinib and Ruxolitinib. J Invest Dermatol. 2017;137(4):951-4. doi: 10.1016/j.jid.2016.10.044
38. Finkelman FD, Madden KB, Morris SC, et al. Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine-anti-cytokine antibody complexes. J Immunol. 1993;151:1235-44.
39. Tavernier J, Tuypens T, Plaetinck G, et al. Molecular basis of the membrane-anchored and two soluble isoforms of the human interleukin 5 receptor alpha subunit. Proc Natl Acad Sci U S A. 1992;89(15):7041-5. doi: 10.1073/pnas.89.15.7041
40. Gevaert P, Hellman C, Lundblad L, et al. Differential expression of the interleukin 5 receptor alpha isoforms in blood and tissue eosinophils of nasal polyp patients. Allergy. 2009 May;64(5):725- 32. doi: 10.1111/j.1398-9995.2008.01885.x
41. Gregory B, Kirchem A, Phipps S, et al. Differential regulation of human eosinophil IL-3, IL-5, and GM-CSF receptor alpha-chain expression by cytokines: IL-3, IL-5, and GM-CSF down-regulate IL-5 receptor alpha expression with loss of IL-5 responsiveness, but up-regulate IL-3 receptor alpha expression. J Immunol. 2003 Jun 1;170(11):5359-66. doi: 10.4049/jimmunol.170.11.5359
42. Flood-Page PT, Menzies-Gow AN, Kay AB, et al. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med. 2003 Jan 15;167(2):199-204. doi: 10.1164/rccm.200208-789OC
43. Nair P, Pizzichini MMM, Kjarsgaard M, et al. Mepolizumab for prednisone dependent asthma with sputum eosinophilia. N Engl J Med. 2009 Mar 5;360(10):985-93. doi: 10.1056/NEJMoa0805435
44. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360:973-84.
45. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, doubleblind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):651-9. doi: 10.1016/S0140-6736(12)60988-X
46. Bel EH, Wenzel SE, Thompson PJ, et al; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291
47. Ortega HG, Liu MC, Pavord ID, et al; MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1198-207. doi: 10.1056/NEJMoa1403290
48. Lugogo N, Domingo C, Chanez P, et al. Long-term efficacy and safety of mepolizumab in patients with severe eosinophilic asthma: a multi-center, open-label, phase IIIb study. Clin Ther. 2016 Sep;38(9):2058-70.e1. doi: 10.1016/j.clinthera.2016.07.010
49. Hillas G, Fouka E, Papaioannou AI. Antibodies targeting the interleukin-5 signaling pathway used as add-on therapy for patients with severe eosinophilic asthma: a review of the mechanism of action, efficacy, and safety of the subcutaneously administered agents, mepolizumab and benralizumab. Expert Rev Respir Med. 2020 Apr;14(4):353-65. doi: 10.1080/17476348.2020.1718495
50. Rothenberg ME, Klion AD, Roufosse FE, et al; Mepolizumab HES Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28. doi: 10.1056/NEJMoa070812
51. Kuang FL, Fay MP, Ware J, et al. Long-term clinical outcomes of high-dose mepolizumab treatment for hypereosinophilic syndrome. J Allergy Clin Immunol Pract. 2018 Sep–Oct;6(5):1518- 27.e5. doi: 10.1016/j.jaip.2018.04.033
52. Roufosse FE, Kahn JE, Gleich GJ, et al. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol. 2013 Feb;131(2):461-7.e1-5. doi: 10.1016/j.jaci.2012.07.055
53. Gevaert P, van Bruaene N, Cattaert T, et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol. 2011 Nov;128(5):989-95.e1-8. doi: 10.1016/j.jaci.2011.07.056
54. Bachert C, Sousa AR, Lund VJ, et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial. J Allergy Clin Immunol. 2017 Oct;140(4):1024-31.e14. doi: 10.1016/j.jaci.2017.05.044
55. Straumann A, Conus S, Grzonka P, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010;59(1):21-30. doi: 10.1136/gut.2009.178558
56. Kang EG, Narayana PK, Pouliquen IJ, et al. Efficacy and safety of mepolizumab administered subcutaneously for moderate to severe atopic dermatitis. Allergy. 2019 Sep 13. doi: 10.1111/all.14050
57. Busse W, Chupp G, Nagase H, et al. Anti-IL-5 treatments in patients with severe asthma by blood eosinophil thresholds: Indirect treatment comparison. J Allergy Clin Immunol. 2019 Jan;143(1):190-200.e20. doi: 10.1016/j.jaci.2018.08.031
58. Mukherjee M, Aleman Paramo F, Kjarsgaard M, et al. Weightadjusted intravenous reslizumab in severe asthma with inadequate response to fixed-dose subcutaneous mepolizumab. Am J Respir Crit Care Med. 2018 Jan 1;197(1):38-46. doi: 10.1164/rccm.201707-1323OC
59. Ortega H, Yancey S, Cozens S. Pharmacokinetics and absolute bioavailability of mepolizumab following administration at subcutaneous and intramuscular sites. Clin Pharmacol Drug Dev. 2014 Jan;3(1):57-62. doi: 10.1002/cpdd.60
60. Kim S, Marigowda G, Oren E, et al. Mepolizumab as a steroidsparing treatment option in patients with Churg-Strauss syndrome. J Allergy Clin Immunol. 2010;125:1336-43. doi: 10.1016/j.jaci.2010.03.028
61. Moosig F, Gross WL, Herrmann K, et al. Targeting interleukin-5 in refractory and relapsing Churg-Strauss syndrome. Ann Intern Med. 2011;155(5):341-3. doi: 10.7326/0003-4819-155-5-201109060-00026
Для цитирования:
Бекетова Т.В., Арсеньев Е.В. Интерлейкин 5 – новая мишень для терапии эозинофильного гранулематоза с полиангиитом. Научно-практическая ревматология. 2020;58(3):321-329. https://doi.org/10.14412/1995-4484-2020-321-329
For citation:
Beketova T.V., Arseniev E.V. INTERLEUKIN-5 IS A NEW TARGET IN THE TREATMENT OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS. Rheumatology Science and Practice. 2020;58(3):321-329. (In Russ.) https://doi.org/10.14412/1995-4484-2020-321-329
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