Efficacy and Safety of Benralizumab, a Monoclonal Antibody against IL-5Rα, in Uncontrolled Eosinophilic Asthma

REFERENCES

• To T, Stanojevic S, Moores G, Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health. 2012;12:204.
   PubMed Web of Science ®Google Scholar
• Wechsler ME. Getting control of uncontrolled asthma. Am J Med. 2014;127(11):1049–59.
   PubMed Web of Science ®Google Scholar
• Braman SS. The global burden of asthma. Chest. 2006;130(1 Suppl):4s–12s.
   PubMed Web of Science ®Google Scholar
• Prevention USCfDCa. National Surveillance of Asthma: United States, 2001–2010 2012 [August 27, 2015]. Available from: http://www.cdc.gov/nchs/data/series/sr_03/sr03_035.pdf.
   Google Scholar
• World Health Organization. Global Burden of Disease report 2004 update [22 June 2015]. Available from: http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf?ua=1.
   Google Scholar
• Hambly N, Nair P. Monoclonal antibodies for the treatment of refractory asthma. Curr Opin Pulm Med. 2014;20(1):87–94.
   PubMed Web of Science ®Google Scholar
• Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118(11):3546–3556.
   PubMed Web of Science ®Google Scholar
• Poon AH, Eidelman DH, Martin JG, Laprise C, Hamid Q. Pathogenesis of severe asthma. Clin Exp Allergy. 2012;42(5):625–637.
   PubMed Web of Science ®Google Scholar
• Hogan SP, Rosenberg HF, Moqbel R, Eosinophils: biological properties and role in health and disease. Clin Exp Allergy. 2008;38(5):709–750.
   PubMed Web of Science ®Google Scholar
• Akuthota P, Wang HB, Spencer LA, Weller PF. Immunoregulatory roles of eosinophils: a new look at a familiar cell. Clin Exp Allergy. 2008;38(8):1254–1263.
   PubMed Web of Science ®Google Scholar
• Woodruff PG, Modrek B, Choy DF, T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180(5):388–395.
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Stoll SJ, Ahn J, Bittner JC, Camargo CA Jr,. Prevalence of eosinophilia in hospitalized patients with asthma exacerbation. Respir Med. 2015.
   PubMed Web of Science ®Google Scholar
• Dente FL, Bacci E, Bartoli ML, Magnitude of late asthmatic response to allergen in relation to baseline and allergen-induced sputum eosinophilia in mild asthmatic patients. Ann Allergy Asthma Immunol. 2008;100(5):457–462.
   PubMed Web of Science ®Google Scholar
• Ulrik CS, Frederiksen J. Mortality and markers of risk of asthma death among 1,075 outpatients with asthma. Chest. 1995;108(1):10–15.
   PubMed Web of Science ®Google Scholar
• Chlumsky J, Striz I, Terl M, Vondracek J. Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma. J Int Med Res. 2006;34(2):129–139.
   PubMed Web of Science ®Google Scholar
• Green RH, Brightling CE, McKenna S, Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet (London, England). 2002;360(9347):1715–1721.
   PubMed Web of Science ®Google Scholar
• Jayaram L, Pizzichini MM, Cook RJ, Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J. 2006;27(3):483–494.
   PubMed Web of Science ®Google Scholar
• Takatsu K, Takaki S, Hitoshi Y. Interleukin-5 and its receptor system: implications in the immune system and inflammation. Adv Immunol. 1994;57:145–190.
   PubMed Web of Science ®Google Scholar
• Rosenberg HF, Phipps S, Foster PS. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol. 2007;119(6):1303–1310; quiz 11–12.
   PubMed Web of Science ®Google Scholar
• Hamid Q, Azzawi M, Ying S, Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest. 1991;87(5):1541–1546.
   PubMed Web of Science ®Google Scholar
• Humbert M, Corrigan CJ, Kimmitt P, Till SJ, Kay AB, Durham SR. Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. Am J Respir Crit Care Med. 1997;156(3 Pt 1):704–708.
   PubMed Web of Science ®Google Scholar
• Robinson D, Hamid Q, Bentley A, Ying S, Kay AB, Durham SR. Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J Allergy Clin Immunol. 1993;92(2):313–324.
   PubMed Web of Science ®Google Scholar
• Hilvering B, Xue L, Pavord ID. Evidence for the efficacy and safety of anti-interleukin-5 treatment in the management of refractory eosinophilic asthma. Ther Adv Respir Dis. 2015.
   PubMed Web of Science ®Google Scholar
• Peacock CD, Misso NL, Watkins DN, Thompson PJ. PGE 2 and dibutyryl cyclic adenosine monophosphate prolong eosinophil survival in vitro. J Allergy Clin Immunol. 1999;104(1):153–162.
   PubMed Web of Science ®Google Scholar
• Tai PC, Sun L, Spry CJ. Effects of IL-5, granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-3 on the survival of human blood eosinophils in vitro. Clin Exp Immunol. 1991;85(2):312–316.
   PubMed Web of Science ®Google Scholar
• Koike M, Nakamura K, Furuya A, Establishment of humanized anti-interleukin-5 receptor alpha chain monoclonal antibodies having a potent neutralizing activity. Hum Antibodies. 2009;18(1-2):17–27.
   PubMedGoogle Scholar
• Tavernier J, Devos R, Cornelis S, A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF. Cell. 1991;66(6):1175–1184.
   PubMed Web of Science ®Google Scholar
• Ogata N, Kouro T, Yamada A, JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation. Blood. 1998;91(7):2264–2271.
   PubMed Web of Science ®Google Scholar
• Takaki S, Kanazawa H, Shiiba M, Takatsu K. A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction. Mol Cell Biol. 1994;14(11):7404–7413.
   PubMed Web of Science ®Google Scholar
• Kolbeck R, Kozhich A, Koike M, 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):1344-1453.e2.
   Web of Science ®Google Scholar
• Ishino T, Pasut G, Scibek J, Chaiken I. Kinetic interaction analysis of human interleukin 5 receptor alpha mutants reveals a unique binding topology and charge distribution for cytokine recognition. J Biol Chem. 2004;279(10):9547–9556.
   PubMed Web of Science ®Google Scholar
• Erjefalt JS, Persson CG. New aspects of degranulation and fates of airway mucosal eosinophils. Am J Respir Crit Care Med. 2000;161(6):2074–2085.
   PubMed Web of Science ®Google Scholar
• Busse WW, Katial R, Gossage D, 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.
   PubMed Web of Science ®Google Scholar
• Corrigan CJ, Haczku A, Gemou-Engesaeth V, CD4 T-lymphocyte activation in asthma is accompanied by increased serum concentrations of interleukin-5. Effect of glucocorticoid therapy. Am Rev Respir Dis. 1993;147(3):540–547.
   PubMed Web of Science ®Google Scholar
• Sahid El-Radhi A, Hogg CL, Bungre JK, Bush A, Corrigan CJ. Effect of oral glucocorticoid treatment on serum inflammatory markers in acute asthma. Arch Dis Child. 2000;83(2):158–162.
   PubMed Web of Science ®Google Scholar
• Stein ML, Villanueva JM, Buckmeier BK, Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol. 2008;121(6):1473–1483, 83.e1–83e4.
   PubMed Web of Science ®Google Scholar
• Wilson TM, Maric I, Shukla J, IL-5 receptor alpha levels in patients with marked eosinophilia or mastocytosis. J Allergy Clin Immunol. 2011;128(5):1086–1092.e1-3.
   PubMed Web of Science ®Google Scholar
• Liu LY, Sedgwick JB, Bates ME, Decreased expression of membrane IL-5 receptor alpha on human eosinophils: I. Loss of membrane IL-5 receptor alpha on airway eosinophils and increased soluble IL-5 receptor alpha in the airway after allergen challenge. J Immunol (Baltimore, MD: 1950). 2002;169(11):6452–6458.
   PubMed Web of Science ®Google Scholar
• van Meerten T, van Rijn RS, Hol S, Hagenbeek A, Ebeling SB. Complement-induced cell death by rituximab depends on CD20 expression level and acts complementary to antibody-dependent cellular cytotoxicity. Clin Cancer Res. 2006;12(13):4027–4035.
   PubMed Web of Science ®Google Scholar
• Iida S, Misaka H, Inoue M, Nonfucosylated therapeutic IgG1 antibody can evade the inhibitory effect of serum immunoglobulin G on antibody-dependent cellular cytotoxicity through its high binding to FcgammaRIIIa. Clin Cancer Res. 2006;12(9):2879–2887.
   PubMed Web of Science ®Google Scholar
• Laviolette M, Gossage DL, Gauvreau G, Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013;132(5):1086–1096.e5.
   PubMed Web of Science ®Google Scholar
• Assa’ad AH, Rothenberg ME. Eosinophilic asthma: insights into the effects of reducing IL-5 receptor-positive cell levels. J Allergy Clin Immunol. 2013;132(5):1097–1098.
   PubMed Web of Science ®Google Scholar
• Wedemeyer J, Tsai M, Galli SJ. Roles of mast cells and basophils in innate and acquired immunity. Curr Opin Immunol. 2000;12(6):624–631.
   PubMed Web of Science ®Google Scholar
• Castro M, Wenzel SE, Bleecker ER, Benralizumab, an anti-interleukin 5 receptor alpha monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med. 2014;2(11):879-90.
   PubMed Web of Science ®Google Scholar
• Khatry DB, Gossage DL, Geba GP, Parker JM, Jarjour NN, Busse WW, Discriminating sputum-eosinophilic asthma: Accuracy of cutoffs in blood eosinophil measurements versus a composite index, ELEN. J Allergy Clin Immunol. 2015.
   PubMed Web of Science ®Google Scholar
• Nowak RM, Parker JM, Silverman RA, Rowe BH, Smithline H, Khan F, A randomized trial of benralizumab, an antiinterleukin 5 receptor alpha monoclonal antibody, after acute asthma. The American journal of emergency medicine. 2015;33(1):14-20.
   PubMed Web of Science ®Google Scholar
• Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of COPD Jan, 2014 [June 23, 2015]. Available from: http://www.goldcopd.org/guidelines-globalstrategy-for-diagnosis-management.html.
   Google Scholar
• Pavord ID. Eosinophilic phenotypes of airway disease. Annals of the American Thoracic Society. 2013;10(Suppl):S143-9.
   PubMedGoogle Scholar
• Bafadhel M, Davies L, Calverley PM, Aaron SD, Brightling CE, Pavord ID. Blood eosinophil guided prednisolone therapy for exacerbations of COPD: a further analysis. Eur Respir J. 2014;44(3):789-91.
   PubMed Web of Science ®Google Scholar
• Siva R, Green RH, Brightling CE, Shelley M, Hargadon B, McKenna S, Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007;29(5):906-13.
   PubMed Web of Science ®Google Scholar
• Brightling CE, Bleecker ER, Panettieri RA Jr., Bafadhel M, She D, Ward CK, Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014;2(11):891–901.
   PubMed Web of Science ®Google Scholar
• Global Initiative on Asthma (GINA). Global strategy for asthma management and prevention Apr, 2015 [June 23, 2015]. Available from: http://www.ginasthma.org.
   Google Scholar
• Bafadhel M, McKenna S, Terry S, Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2012;186(1):48–55.
   PubMed Web of Science ®Google Scholar
• Juhlin L, Michaelsson G. A new syndrome characterised by absence of eosinophils and basophils. Lancet (London, England). 1977;1(8024):1233–1235.
   PubMed Web of Science ®Google Scholar
• Mitchell EB, Platts-Mills TA, Pereira RS, Malkovska V, Webster AD. Acquired basophil and eosinophil deficiency in a patient with hypogammaglobulinaemia associated with thymoma. Clin Lab Haematol. 1983;5(3):253–527.
   PubMedGoogle Scholar
• Leckie MJ, ten Brinke A, Khan J, Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet (London, England). 2000;356(9248):2144–2148.
   PubMed Web of Science ®Google Scholar
• Kips JC, O’Connor BJ, Langley SJ, 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):1655–1659.
   PubMed Web of Science ®Google Scholar
• Castro M, Mathur S, Hargreave F, Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011;184(10):1125–1132.
   PubMed Web of Science ®Google Scholar
• Menzies-Gow A, Flood-Page P, Sehmi R, Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics. J Allergy Clin Immunol. 2003;111(4):714–719.
   PubMed Web of Science ®Google Scholar
• Haldar P, Brightling CE, Hargadon B, Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360(10):973–984.
   PubMed Web of Science ®Google Scholar
• Flood-Page P, Menzies-Gow A, Phipps S, Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest. 2003;112(7):1029–1036.
   PubMed Web of Science ®Google Scholar
• Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med. 2003;167(2):199–204.
   PubMed Web of Science ®Google Scholar
• Flood-Page P, Swenson C, Faiferman I, A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007;176(11):1062–1071.
   PubMed Web of Science ®Google Scholar
• Nair P, Pizzichini MM, Kjarsgaard M, Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360(10):985–993.
   PubMed Web of Science ®Google Scholar
• Bel EH, Wenzel SE, Thompson PJ, Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189–1197.
   PubMed Web of Science ®Google Scholar
• Ortega HG, Liu MC, Pavord ID, Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198–1207.
   PubMed Web of Science ®Google Scholar
• Castro M, Zangrilli J, Wechsler ME, 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):355–366.
   PubMed Web of Science ®Google Scholar
• Katz LE, Gleich GJ, Hartley BF, Yancey SW, Ortega HG. Blood eosinophil count is a useful biomarker to identify patients with severe eosinophilic asthma. Ann Am Thorac Soc. 2014;11(4):531–536.
   PubMedGoogle Scholar
• Al-Samri MT, Benedetti A, Prefontaine D, Variability of sputum inflammatory cells in asthmatic patients receiving corticosteroid therapy: A prospective study using multiple samples. J Allergy Clin Immunol. 2010;125(5):1161–1163.e4.
   PubMed Web of Science ®Google Scholar
• Bellido-Casado J, Plaza V, Perpina M, Inflammatory response of rapid onset asthma exacerbation. Arch Bronconeumol. 2010;46(11):587–593.
   PubMed Web of Science ®Google Scholar