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A Review of Anti-IL-5 Therapies for Eosinophilic Granulomatosis with Polyangiitis

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A Correction to this article was published on 12 November 2022

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Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg–Strauss syndrome, is a systemic disorder characterized by asthma, eosinophilia, and vasculitis primarily affecting small vessels. Although this disease is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis along with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), observations suggest that eosinophils play a vital role in the pathophysiology of EGPA. Therefore, biopsy specimens derived from patients with EGPA demonstrated an increase in eosinophils within the vascular lumen and extravascular interstitium, especially in patients negative for ANCA. In addition, active secretion of eosinophil intracellular components by cytolysis and piecemeal degranulation occurs in the extravascular interstitium and bloodstream. Although the treatment for EGPA is described in the context of ANCA-associated vasculitis along with MPA and GPA, a therapeutic approach to suppress eosinophils is also considered. Monoclonal antibodies directed against interleukin-5 (IL-5) or its receptors are good therapeutic agents because IL-5 plays an important role in eosinophil growth, activation, and survival. Currently, mepolizumab (Nucala), reslizumab (Cinqair), and benralizumab (Fasenra) have been studied for use in patients with EGPA. These monoclonal antibodies were initially approved for use in patients with severe eosinophilic asthma. Mepolizumab is now approved for treating EGPA following the success of phase 3 randomized controlled trial. Therefore, further studies are needed to clarify long-term safety and efficacy of anti-IL-5 agents and establish indications of individual therapeutic agents tailored to individual conditions of patients with EGPA.

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References

  1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum. 2013;65(1):1–11.

    Article  CAS  Google Scholar 

  2. Koike H, Nishi R, Ohyama K, et al. ANCA-associated vasculitic neuropathies: a review. Neurol Ther. 2022;11(1):21–38.

    Article  Google Scholar 

  3. Koike H, Sobue G. Clinicopathological features of neuropathy in anti-neutrophil cytoplasmic antibody-associated vasculitis. Clin Exp Nephrol. 2013;17(5):683–5.

    Article  CAS  Google Scholar 

  4. Sinico RA, Di Toma L, Maggiore U, et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis Rheum. 2005;52(9):2926–35.

    Article  CAS  Google Scholar 

  5. Sablé-Fourtassou R, Cohen P, Mahr A, et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med. 2005;143(9):632–8.

  6. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116(6):488–98.

    Article  CAS  Google Scholar 

  7. Guillevin L, Durand-Gasselin B, Cevallos R, et al. Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum. 1999;42(3):421–30.

    Article  CAS  Google Scholar 

  8. Nishi R, Koike H, Ohyama K, et al. Differential clinicopathologic features of EGPA-associated neuropathy with and without ANCA. Neurology. 2020;94(16):e1726–37.

    Article  CAS  Google Scholar 

  9. Koike H, Nishi R, Furukawa S, et al. In vivo visualization of eosinophil secretion in eosinophilic granulomatosis with polyangiitis: an ultrastructural study. Allergol Int. 2022;71(3):373–82.

    Article  CAS  Google Scholar 

  10. Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017;376(20):1921–32.

  11. Grayson PC, Ponte C, Suppiah R, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis. 2022;81(3):309–314.

  12. Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore). 1999;78(1):26–37.

  13. Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990;33(8):1094–100.

    Article  CAS  Google Scholar 

  14. Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. 1994;37(2):187–92.

  15. Radice A, Bianchi L, Sinico RA. Anti-neutrophil cytoplasmic autoantibodies: methodological aspects and clinical significance in systemic vasculitis. Autoimmun Rev. 2013;12(4):487–95.

    Article  CAS  Google Scholar 

  16. Takahashi M, Koike H, Ikeda S, et al. Distinct pathogenesis in nonsystemic vasculitic neuropathy and microscopic polyangiitis. Neurol Neuroimmunol Neuroinflamm. 2017;4(6):e407.

    Article  Google Scholar 

  17. Stone JH, Wegener's Granulomatosis Etanercept Trial Research Group. Limited versus severe Wegener's granulomatosis: baseline data on patients in the Wegener's granulomatosis etanercept trial. Arthritis Rheum. 2003;48(8):2299–309.

  18. Healy B, Bibby S, Steele R, Weatherall M, Nelson H, Beasley R. Antineutrophil cytoplasmic autoantibodies and myeloperoxidase autoantibodies in clinical expression of Churg-Strauss syndrome. J Allergy Clin Immunol. 2013;131(2):571–6.e1–6.

  19. Comarmond C, Pagnoux C, Khellaf M, et al. 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;65(1):270–81.

  20. Lyons PA, Peters JE, Alberici F, et al. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat Commun. 2019;10(1):5120.

  21. Mahr A, Guillevin L, Poissonnet M, Aymé S. Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener’s granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: a capture-recapture estimate. Arthritis Rheum. 2004;51(1):92–9.

    Article  Google Scholar 

  22. Watts RA, Lane S, Scott DG. What is known about the epidemiology of the vasculitides? Best Pract Res Clin Rheumatol. 2005;19(2):191–207.

    Article  Google Scholar 

  23. Mohammad AJ, Jacobsson LT, Mahr AD, Sturfelt G, Segelmark M. Prevalence of Wegener’s granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome within a defined population in southern Sweden. Rheumatology (Oxford). 2007;46(8):1329–37.

    Article  CAS  Google Scholar 

  24. Sada KE, Kojo Y, Fairburn-Beech J, et al. The prevalence, burden of disease, and healthcare utilization of patients with eosinophilic granulomatosis with polyangiitis in Japan: a retrospective, descriptive cohort claims database study. Mod Rheumatol. 2022;32(2):380–6.

    Article  Google Scholar 

  25. Xiao H, Heeringa P, Hu P, et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest. 2002;110(7):955–63.

    Article  CAS  Google Scholar 

  26. Little MA, Smyth CL, Yadav R, et al. Antineutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte-microvascular interactions in vivo. Blood. 2005;106(6):2050–8.

    Article  CAS  Google Scholar 

  27. Falk RJ, Terrell RS, Charles LA, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci U S A. 1990;87(11):4115–9.

    Article  CAS  Google Scholar 

  28. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–5.

    Article  CAS  Google Scholar 

  29. Yipp BG, Petri B, Salina D, et al. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med. 2012;18(9):1386–93.

    Article  CAS  Google Scholar 

  30. Kessenbrock K, Krumbholz M, Schönermarck U, et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med. 2009;15(6):623–5.

    Article  CAS  Google Scholar 

  31. Lee KH, Kronbichler A, Park DD, et al. Neutrophil extracellular traps (NETs) in autoimmune diseases: a comprehensive review. Autoimmun Rev. 2017;16(11):1160–73.

    Article  CAS  Google Scholar 

  32. Natorska J, Ząbczyk M, Siudut J, Krawiec P, Mastalerz L, Undas A. Neutrophil extracellular traps formation in patients with eosinophilic granulomatosis with polyangiitis: association with eosinophilic inflammation. Clin Exp Rheumatol. 2017;35 Suppl 103(1):27–32.

  33. Nishi R, Koike H, Ohyama K, et al. Association between IL-5 levels and the clinicopathologic features of eosinophilic granulomatosis with polyangiitis. Neurology. 2021;96(5):226–9.

    Article  CAS  Google Scholar 

  34. Koike H, Furukawa S, Mouri N, Fukami Y, Iijima M, Katsuno M. Early ultrastructural lesions of anti-neutrophil cytoplasmic antibody- versus complement-associated vasculitis. Neuropathology. https://doi.org/10.1111/neup.12821.

  35. Kanda A, Yun Y, Bui DV, et al. The multiple functions and subpopulations of eosinophils in tissues under steady-state and pathological conditions. Allergol Int. 2021;70(1):9–18.

    Article  CAS  Google Scholar 

  36. Lombardi C, Berti A, Cottini M. The emerging roles of eosinophils: Implications for the targeted treatment of eosinophilic-associated inflammatory conditions. Curr Res Immunol. 2022;21(3):42–53.

    Article  Google Scholar 

  37. Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017;17(12):746–60.

    Article  CAS  Google Scholar 

  38. Saffari H, Hoffman LH, Peterson KA, et al. Electron microscopy elucidates eosinophil degranulation patterns in patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2014;133(6):1728–34.e1.

    Article  CAS  Google Scholar 

  39. Neves JS, Perez SA, Spencer LA, et al. Eosinophil granules function extracellularly as receptor-mediated secretory organelles. Proc Natl Acad Sci U S A. 2008;105(47):18478–83.

    Article  CAS  Google Scholar 

  40. Woerly G, Roger N, Loiseau S, Dombrowicz D, Capron A, Capron M. Expression of CD28 and CD86 by human eosinophils and role in the secretion of type 1 cytokines (interleukin 2 and interferon gamma): inhibition by immunoglobulin a complexes. J Exp Med. 1999;190(4):487–95.

    Article  CAS  Google Scholar 

  41. Spencer LA, Bonjour K, Melo RC, Weller PF. Eosinophil secretion of granule-derived cytokines. Front Immunol. 2014;27(5):496. https://doi.org/10.3389/fimmu.2014.

    Article  Google Scholar 

  42. Melo RCN, Weller PF. Contemporary understanding of the secretory granules in human eosinophils. J Leukoc Biol. 2018;104(1):85–93.

    Article  CAS  Google Scholar 

  43. Fukuchi M, Miyabe Y, Furutani C, et al. How to detect eosinophil ETosis (EETosis) and extracellular traps. Allergol Int. 2021;70(1):19–29.

    Article  CAS  Google Scholar 

  44. Hashimoto T, Ueki S, Kamide Y, et al. Increased circulating cell-free DNA in eosinophilic granulomatosis with polyangiitis: implications for eosinophil extracellular traps and immunothrombosis. Front Immunol. 2022;12(12):801897.

    Article  Google Scholar 

  45. Malm-Erjefält M, Greiff L, Ankerst J, et al. Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation. Clin Exp Allergy. 2005;35(10):1334–40.

    Article  Google Scholar 

  46. Uderhardt S, Ackermann JA, Fillep T, et al. Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease. J Exp Med. 2017;214(7):2121–38.

    Article  CAS  Google Scholar 

  47. Marx C, Novotny J, Salbeck D, et al. Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps. Blood. 2019;134(21):1859–72.

    Article  CAS  Google Scholar 

  48. Bettiol A, Sinico RA, Schiavon F, et al. Risk of acute arterial and venous thromboembolic events in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Eur Respir J. 2021;57(5):2004158.

  49. Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016;75(9):1583–94.

    Article  CAS  Google Scholar 

  50. Wallace ZS, Miloslavsky EM. Management of ANCA associated vasculitis. BMJ. 2020;18(368): m421.

    Article  Google Scholar 

  51. Groh M, Pagnoux C, Baldini C, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management. Eur J Intern Med. 2015;26(7):545–53.

    Article  Google Scholar 

  52. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2021;73(8):1366–83.

    Article  CAS  Google Scholar 

  53. Durel CA, Berthiller J, Caboni S, Jayne D, Ninet J, Hot A. Long-term followup of a multicenter cohort of 101 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Arthritis Care Res (Hoboken). 2016;68(3):374–87.

    Article  Google Scholar 

  54. Gokhale M, Bell CF, Doyle S, Fairburn-Beech J, Steinfeld J, Van Dyke MK. Prevalence of eosinophilic granulomatosis with polyangiitis and associated health care utilization among patients with concomitant asthma in US commercial claims database. J Clin Rheumatol. 2021;27(3):107–13.

    Article  Google Scholar 

  55. Koike H, Akiyama K, Saito T, Sobue G, Research Group for IVIg for EGPA/CSS in Japan. Intravenous immunoglobulin for chronic residual peripheral neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a multicenter, double-blind trial. J Neurol. 2015;262(3):752–9.

  56. Jayne DR, Chapel H, Adu D, et al. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM. 2000;93(7):433–9.

    Article  CAS  Google Scholar 

  57. Crickx E, Machelart I, Lazaro E, et al. Intravenous immunoglobulin as an immunomodulating agent in antineutrophil cytoplasmic antibody-associated vasculitides: a French nationwide study of ninety-two patients. Arthritis Rheumatol. 2016;68(3):702–12.

  58. Molfino NA, Gossage D, Kolbeck R, Parker JM, Geba GP. Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin Exp Allergy. 2012;42(5):712–37.

    Article  CAS  Google Scholar 

  59. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013;13(1):9–22.

    Article  CAS  Google Scholar 

  60. Akdis CA, Arkwright PD, Brüggen MC, et al. Type 2 immunity in the skin and lungs. Allergy. 2020;75(7):1582–605.

    Article  CAS  Google Scholar 

  61. Nagase H, Ueki S, Fujieda S. The roles of IL-5 and anti-IL-5 treatment in eosinophilic diseases: asthma, eosinophilic granulomatosis with polyangiitis, and eosinophilic chronic rhinosinusitis. Allergol Int. 2020;69(2):178–86.

    Article  CAS  Google Scholar 

  62. Nussbaum JC, Van Dyken SJ, von Moltke J, et al. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature. 2013;502(7470):245–8.

    Article  CAS  Google Scholar 

  63. Kabata H, Moro K, Koyasu S, Asano K. Group 2 innate lymphoid cells and asthma. Allergol Int. 2015;64(3):227–34.

    Article  CAS  Google Scholar 

  64. Pavord ID, Bel EH, Bourdin A, et al. From DREAM to REALITI-A and beyond: mepolizumab for the treatment of eosinophil-driven diseases. Allergy. 2022;77(3):778–97.

    Article  CAS  Google Scholar 

  65. Kopf M, Brombacher F, Hodgkin PD, et al. IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity. 1996;4(1):15–24.

    Article  CAS  Google Scholar 

  66. Dent LA, Strath M, Mellor AL, Sanderson CJ. Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med. 1990;172(5):1425–31.

    Article  CAS  Google Scholar 

  67. Prakash Babu S, Chen YK, Bonne-Annee S, et al. Dysregulation of interleukin 5 expression in familial eosinophilia. Allergy. 2017;72(9):1338–45.

    Article  CAS  Google Scholar 

  68. Jakiela B, Szczeklik W, Plutecka H, et al. Increased production of IL-5 and dominant Th2-type response in airways of Churg-Strauss syndrome patients. Rheumatology (Oxford). 2012;51(10):1887–93.

    Article  CAS  Google Scholar 

  69. Bagnasco D, Ferrando M, Varricchi G, Puggioni F, Passalacqua G, Canonica GW. Anti-interleukin 5 (IL-5) and IL-5Ra biological drugs: efficacy, safety, and future perspectives in severe eosinophilic asthma. Front Med (Lausanne). 2017;31(4):135.

    Article  Google Scholar 

  70. Plötz SG, Simon HU, Darsow U, et al. Use of an anti-interleukin-5 antibody in the hypereosinophilic syndrome with eosinophilic dermatitis. N Engl J Med. 2003;349(24):2334–9.

    Article  Google Scholar 

  71. Stein ML, Collins MH, Villanueva JM, et al. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol. 2006;118(6):1312–9.

    Article  CAS  Google Scholar 

  72. Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000;356(9248):2144–8.

  73. Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007;176(11):1062–71.

  74. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651–9.

    Article  CAS  Google Scholar 

  75. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198–207.

  76. Roufosse F, Kahn JE, Rothenberg ME. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: a phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020;146(6):1397–1405.

  77. Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;9(10):1141–53.

  78. Kahn JE, Grandpeix-Guyodo C, Marroun I, et al. Sustained response to mepolizumab in refractory Churg-Strauss syndrome. J Allergy Clin Immunol. 2010;125(1):267–70.

    Article  CAS  Google Scholar 

  79. Kim S, Marigowda G, Oren E, Israel E, Wechsler ME. Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome. J Allergy Clin Immunol. 2010;125(6):1336–43.

    Article  CAS  Google Scholar 

  80. Moosig F, Gross WL, Herrmann K, Bremer JP, Hellmich B. Targeting interleukin-5 in refractory and relapsing Churg-Strauss syndrome. Ann Intern Med. 2011;155(5):341–3.

    Article  Google Scholar 

  81. Vultaggio A, Nencini F, Bormioli S, et al. Low-dose mepolizumab effectiveness in patients suffering from eosinophilic granulomatosis with polyangiitis. Allergy Asthma Immunol Res. 2020;12(5):885–93.

    Article  CAS  Google Scholar 

  82. Bettiol A, Urban ML, Dagna L, et al. Mepolizumab for eosinophilic granulomatosis with polyangiitis: a European multicenter observational study. Arthritis Rheumatol. 2022;74(2):295–306.

  83. Uzzo M, Regola F, Trezzi B, Toniati P, Franceschini F, Sinico RA. Novel targets for drug use in eosinophilic granulomatosis with polyangiitis. Front Med (Lausanne). 2021;2(8):754434.

    Article  Google Scholar 

  84. Kips JC, O’Connor BJ, Langley SJ, et al. Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med. 2003;167(12):1655–9.

    Article  Google Scholar 

  85. Gevaert P, Lang-Loidolt D, Lackner A, et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol. 2006;118(5):1133–41.

    Article  CAS  Google Scholar 

  86. Castro M, Mathur S, Hargreave F, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011;184(10):1125–32.

  87. Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015;3(5):355–66.

    Article  CAS  Google Scholar 

  88. Kent BD, d’Ancona G, Fernandes M, et al. Oral corticosteroid-sparing effects of reslizumab in the treatment of eosinophilic granulomatosis with polyangiitis. ERJ Open Res. 2020;6(1):00311–2019.

    Article  Google Scholar 

  89. Manka LA, Guntur VP, Denson JL, et al. Efficacy and safety of reslizumab in the treatment of eosinophilic granulomatosis with polyangiitis. Ann Allergy Asthma Immunol. 2021;126(6):696-701.e1.

    Article  CAS  Google Scholar 

  90. Ghazi A, Trikha A, Calhoun WJ. Benralizumab–a humanized mAb to IL-5Rα with enhanced antibody-dependent cell-mediated cytotoxicity–a novel approach for the treatment of asthma. Expert Opin Biol Ther. 2012;12(1):113–8.

    Article  CAS  Google Scholar 

  91. Kolbeck R, Kozhich A, Koike M, et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125(6):1344–1353.e2.

    Article  CAS  Google Scholar 

  92. Busse WW, Katial R, Gossage D, et al. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol. 2010;125(6):1237–1244.e2.

    Article  CAS  Google Scholar 

  93. Laviolette M, Gossage DL, Gauvreau G, et al. Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013;132(5):1086–1096.e5.

    Article  CAS  Google Scholar 

  94. Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115–27.

  95. FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128–41.

  96. Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25):2448–58.

  97. Takenaka K, Minami T, Yoshihashi Y, Hirata S, Kimura Y, Kono H. Decrease in MPO-ANCA after administration of benralizumab in eosinophilic granulomatosis with polyangiitis. Allergol Int. 2019;68(4):539–40.

    Article  Google Scholar 

  98. Colantuono S, Pellicano C, Leodori G, Cilia F, Francone M, Visentini M. Early benralizumab for eosinophilic myocarditis in eosinophilic granulomatosis with polyangiitis. Allergol Int. 2020;69(3):483–4.

    Article  Google Scholar 

  99. Coppola A, Flores KR, De Filippis F. Rapid onset of effect of benralizumab on respiratory symptoms in a patient with eosinophilic granulomatosis with polyangiitis. Respir Med Case Rep. 2020;4(30): 101050.

    Google Scholar 

  100. Guntur VP, Manka LA, Denson JL, et al. Benralizumab as a steroid-sparing treatment option in eosinophilic granulomatosis with polyangiitis. J Allergy Clin Immunol Pract. 2021;9(3):1186–1193.e1.

    Article  CAS  Google Scholar 

  101. Padoan R, Chieco Bianchi F, Marchi MR, et al. Benralizumab as a glucocorticoid-sparing treatment option for severe asthma in eosinophilic granulomatosis with polyangiitis. J Allergy Clin Immunol Pract. 2020;8(9):3225–3227.e2.

    Article  Google Scholar 

  102. Menzella F, Galeone C, Ghidoni G, et al. Successful treatment with benralizumab in a patient with eosinophilic granulomatosis with polyangiitis refractory to mepolizumab. Multidiscip Respir Med. 2021;16(1):779.

    Google Scholar 

  103. Ford JA, Aleatany Y, Gewurz-Singer O. Therapeutic advances in eosinophilic granulomatosis with polyangiitis. Curr Opin Rheumatol. 2022;34(3):158–64.

    Article  CAS  Google Scholar 

  104. Bello F, Emmi G, Tamburini C, et al. Eosinophilic granulomatosis with polyangiitis-related myocarditis during mepolizumab therapy reveals a Th1/Th17-mediated vasculitic response. Clin Exp Rheumatol. 2022;40(4):863–4.

    Google Scholar 

  105. Gleich GJ, Klion AD, Lee JJ, Weller PF. The consequences of not having eosinophils. Allergy. 2013;68(7):829–35.

    Article  CAS  Google Scholar 

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Acknowledgments

Funding

This work was supported in part by the Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labour and Welfare of Japan (20FC1030) and JSPS KAKENHI (20K07882). No funding was received for the publication of this work.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Disclosures

Haruki Koike, Ryoji Nishi, Satoru Yagi, Soma Furukawa, Yuki Fukami, Masahiro Iijima, and Masahisa Katsuno have nothing to disclose.

Author Contributions

Haruki Koike developed the concept of the article, carried out the literature review, and wrote the first draft. All authors critically evaluated the manuscript.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

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Authors and Affiliations

  1. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurimai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Haruki Koike, Ryoji Nishi, Satoru Yagi, Soma Furukawa, Yuki Fukami, Masahiro Iijima & Masahisa Katsuno

  2. Department of Neurology, Daido Hospital, Nagoya, Japan

    Ryoji Nishi

  3. Department of Clinical Research Education, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Masahisa Katsuno

Authors
  1. Haruki Koike
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  2. Ryoji Nishi
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  3. Satoru Yagi
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  4. Soma Furukawa
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  5. Yuki Fukami
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  6. Masahiro Iijima
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  7. Masahisa Katsuno
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Corresponding author

Correspondence to Haruki Koike.

Additional information

The original online version of this article was revised due to update in table 1.

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Koike, H., Nishi, R., Yagi, S. et al. A Review of Anti-IL-5 Therapies for Eosinophilic Granulomatosis with Polyangiitis. Adv Ther 40, 25–40 (2023). https://doi.org/10.1007/s12325-022-02307-x

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