Profile of anti-IL-5 mAb mepolizumab in the treatment of severe refractory asthma and hypereosinophilic diseases

Journal of Asthma and Allergy

Volumn 8, Issue , 2015, Pages 105-114

  Menzella, Francesco ^a   Lusuardi, Mirco ^b   Galeone, Carla ^a   Taddei, Sofia ^a   Zucchi, Luigi ^a  

^a S MARIA NUOVA HOSPITAL   (Italy)

^b PATHOLOGY UNIT   (Italy)

Author keywords

Asthma; Eosinophils; IL 5; Inflammation; Mepolizumab; Phenotype

Indexed keywords

ALLERGEN; B LYMPHOCYTE DIFFERENTIATION FACTOR; BENRALIZUMAB; CHEMOKINE RECEPTOR CCR3; CORTICOSTEROID; EOTAXIN; EOTAXIN 2; EOTAXIN 3; GELATINASE B; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR RECEPTOR; INTERLEUKIN 13; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 3; INTERLEUKIN 3 RECEPTOR; INTERLEUKIN 4 RECEPTOR; INTERLEUKIN 5; INTERLEUKIN 5 RECEPTOR ALPHA; INTERLEUKIN 6; MEPOLIZUMAB; MONOCYTE CHEMOTACTIC PROTEIN 3; MONOCYTE CHEMOTACTIC PROTEIN 5; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PREDNISONE; RANTES; RESLIZUMAB; THROMBOCYTE ACTIVATING FACTOR RECEPTOR; TRANSCRIPTION FACTOR GATA 3;

ASTHMA; ASTHMA CONTROL QUESTIONNAIRE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL ASSESSMENT; CLINICAL TRIAL (TOPIC); CYTOKINE RELEASE; DISEASE ASSESSMENT; DRUG EFFICACY; DRUG SAFETY; EOSINOPHILIA; EOSINOPHILIC ESOPHAGITIS; FORCED EXPIRATORY VOLUME; HEALTH CARE COST; HUMAN; HYPEREOSINOPHILIC SYNDROME; INFLAMMATION; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POLYPOSIS; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESPIRATORY TRACT ALLERGY; REVIEW; SINONASAL POLYPOSIS; ST GEORGE S RESPIRATORY QUESTIONNAIRE; T LYMPHOCYTE ACTIVATION; TH2 CELL; WEGENER GRANULOMATOSIS;

EID: 84944033186     PISSN: 11786965     EISSN: 11786965     Source Type: Journal    
DOI: 10.2147/JAA.S40244     Document Type: Review

References (76)

1. Accordini S, Corsico AG, Braggion M, et al. The cost of persistent asthma in Europe: an international population-based study in adults. Int Arch Allergy Immunol. 2013;160(1):93–101.
2. Rabe KF, Adachi M, Lai CK, et al. Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. J Allergy Clin Immunol. 2004;114(1):40–47.
3. Wenzel S. Severe asthma: from characteristics to phenotypes to endotypes. Clin Exp Allergy. 2012;42(5):650–658.
4. Manuyakorn W, Howarth PH, Holgate ST. Airway remodelling in asthma and novel therapy. Asian Pac J Allergy Immunol. 2013;31(1): 3–108.
5. Schuijs MJ, Willart MA, Hammad H, Lambrecht BN. Cytokine targets in airway inflammation. Lung damage and airway remodelling in severe asthma. Curr Opin Pharmacol. 2013;13(3):351–361.
6. Brightling CE, Gupta S, Gonem S, Siddiqui S. Lung damage and airway remodelling in severe asthma. Clin Exp Allergy. 2012;42(5):638–649.
7. Fahy JV. Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies. Proc Am Thorac Soc. 2009;16(3):256–259.
8. Pepe C, Foley S, Shannon J, et al. Differences in airway remodeling between subjects with severe and moderate asthma. J Allergy Clin Immunol. 2005;116:544–549.
9. Humbert M, Beasley R, Ayres J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60(3):309–316.
10. Normansell R, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;1:CD003559.
11. Zhang JY, Wenzel SE. Tissue and BAL based biomarkers in asthma. Immunol Allergy Clin North Am. 2007;27:623–632.
12. Bousquet J, Chanez P, Lacoste JY, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990;323:1033–1039.
13. Turner MO, Hussack P, Sears MR, et al. Exacerbations of asthma without sputum eosinophilia. Thorax 1995;50:1057–1061.
14. 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;356:2144–2148.
15. 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.
16. Uhm TG, Kim BS, Chung IY. Eosinophil development, regulation of eosinophil-specific genes, and role of eosinophils in the pathogenesis of asthma. Allergy Asthma Immunol Res. 2012;4(2):68–79.
17. McKinnon M, Bank M, Solari R, Robinson G. Interleukin-5 and the interleukin receptor: targets for drug discovery in asthma. In: Sanderson CJ, editor. Interleukin-5: From molecule to Drug Target for Asthma. New York: Marcel Dekker, Inc.;1999:299–320.
18. Menzies-Gow A, Flood-Page P, Sehmi R, et al. 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.
19. Wells TN, Graber P, Proudfoot AE, et al. The three-dimensional structure of human interleukin-5 at 2.4-angstroms resolution: implication for the structures of other cytokines. Ann N Y Acad Sci. 1994;28(725):118–127.
20. Takatsu K, Nakajima H. IL-5 and eosinophilia. Curr Opin Immunol. 2008;20:288–294.
21. Kouro T, Takatsu K. IL-5- and eosinophil-mediated inflammation: from discovery to therapy. Int Immunol. 2009;21(12):1303–1309.
22. Tanaka H, Komai M, Nagao K, et al. Role of interleukin-5 and eosinophils in allergen-induced airway remodeling in mice. Am J Respir Cell Mol Biol. 2004;31:62.
23. Becchetti E, Bani D, Baroni T., Istologia Umana. Napoli: Idelson-Gnocchi. 2011:393–394. ISBN 9788879475419.
24. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013;13(1):9–22.
25. Valent P. The phenotype of human eosinophils, basophils, and mast cells. J Allergy Clin Immunol. 1994;94:1177–1183.
26. Toba K, Koike T, Shibata A, et al. Novel technique for the direct flow cytofluorometric analysis of human basophils in unseparated blood and bone marrow, and the characterization of phenotype and peroxidase of human basophils. Cytometry 1999;35:249–259.
27. Dahinen CA, Rihs S, Ochsensberger B. Regulation of cytokine expression by human blood basophils. Int Arch Allergy Immunol. 1997;113:134–137
28. Kowal K, Nolte H, Skov PS, et al. Effect of allergen-specific immunotherapy on recombinant human interleukin 3-mediated amplification of allergen-induced basophil histamine release. Allergy Asthma Proc. 2005;26:456–462.
29. Lloyd CM, Rankin SM. Chemokines in allergic airway disease. Curr Opin Pharmacol. 2003;3:443–448.
30. Bochner BS. Siglec-8 on human eosinophils and mast cells, and Siglec-F on murine eosinophils, are functionally related inhibitory receptors. Clin Exp Allergy. 2009;39:317–324.
31. Kvarnhammar AM, Cardell LO. Pattern recognition receptors in human eosinophils. Immunology 2012;136:11–20.
32. Månsson A, Cardell LO. Role of atopic status in Toll-like receptor (TLR)7- and TLR9-mediated activation of human eosinophils. J Leukoc Biol. 2009;85:719–727.
33. Nakagome K, Matsushita S, Nagata M. Neutrophilic inflammation in severe asthma. Int Arch Allergy Immunol. 2012;158(1):96–102.
34. Bafadhel M, McCormick M, Saha S, et al. Profiling of sputum inflammatory mediators in asthma and chronic obstructive pulmonary disease. Respiration 2012;83(1):36–44.
35. Menzella F, Lusuardi M, Galeone C, Zucchi L. Tailored therapy for severe asthma. Multidiscip Respir Med. 2015;10(1):1.
36. 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;176:1062–1071.
37. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360:973–984.
38. Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360:985–993.
39. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380:651–659.
40. 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):355–366.
41. Lim HF, Nair P. Efficacy and safety of reslizumab in patients with moderate to severe eosinophilic asthma. Expert Rev Respir Med. 2015;9(2):135–142.
42. Zia-Amirhosseini P, Minthorn E, Benincosa LJ, et al. Pharmacokinetics and pharmacodynamics of SB-240563, a humanized monoclonal antibody directed to human interleukin-5, in monkeys. J Pharmacol Exp Ther. 1999;291(3):1060–1067.
43. European Medicines Agency. Withdrawal Assessment Report for Bosatria. London, UK: European Medicines Agency; 2009. Doc. Ref: EMEA/454803/2009.
44. Lopez AF, Sanderson CJ, Gamble JR, Campbell HD, Young IG, Vadas MA. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med. 1988;167(1):219–224.
45. Ohnishi T, Sur S, Collins DS, Fish JE, Gleich GJ, Peters SP. Eosinophil survival activity identified as interleukin-5 is associated with eosinophil recruitment and degranulation and lung injury twenty-four hours after segmental antigen lung challenge. J Allergy Clin Immunol. 1993; 92(4):607–615.
46. Clutterbuck EJ, Sanderson CJ. Regulation of human eosinophil precursor production by cytokines: a comparison of recombinant human interleukin-1 (rhIL-1), rhIL-3, rhIL-5, rhIL-6, and rh granulocyte-macrophage colony-stimulating factor. Blood 1990;75(9): 1774–1779.
47. Hart TK, Cook RM, Zia-Amirhosseini P, et al. Preclinical efficacy and safety of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys. J Allergy Clin Immunol. 2001;108(2):250–257.
48. Wenzel SE. Eosinophils in asthma – closing the loop or opening the door? N Engl J Med. 2009;360(10):1026–1028.
49. Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology. 2006;11:54–61.
50. Ortega H, Chupp G, Bardin P, et al. The role of mepolizumab in atopic and nonatopic severe asthma with persistent eosinophilia. Eur Respir J. 2014;44(1):239–241.
51. Ortega H, Li H, Suruki R, Albers F, Gordon D, Yancey S.: Cluster analysis and characterization of response to mepolizumab. A step closer to personalized medicine for patients with severe asthma. Ann Am Thorac Soc. 2014;11(7):1011–1017.
52. Prazma CM, Wenzel S, Barnes N, Douglass JA, Hartley BF, Ortega H. Characterisation of an OCS-dependent severe asthma population treated with mepolizumab. Thorax. 2014;69(12):1141–1142.
53. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198–1207.
54. Haldar P, Brightling CE, Singapuri A, et al. Outcomes after cessation of mepolizumab therapy in severe eosinophilic asthma: a 12-month follow-up analysis. J Allergy Clin Immunol. 2014;133(3):921–923.
55. GlaxoSmithKline. Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants with Severe Eosinophilic Asthma on Markers of Asthma Control; 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT02281318. Accessed June 1, 2015. [NLM Identifier: NCT02281318].
56. Liu Y, Zhang S, Li DW, Jiang SJ. Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials. PLoS One. 2013;8(3):e59872.
57. Nowak RM, Parker JM, Silverman RA, et al. A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma. Am J Emerg Med. 2015;33(1):14–20.
58. Garrett JK, Jameson SC, Thomson B, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004;113(1):115–119.
59. 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;20;358(12):1215–1228.
60. Leiferman KM. A role for eosinophils in atopic dermatitis. J Am Acad Dermatol. 2001;45(1):S21–S24.
61. Wedi B, Raap U, Lewrick H, Kapp A. Delayed eosinophil programmed cell death in vitro: a common feature of inhalant allergy and extrinsic and intrinsic atopic dermatitis. J Allergy Clin Immunol. 1997;100: 536–543.
62. Gnanakumaran G, Babu KS. Technology evaluation: mepolizumab, GlaxoSmithKline. Curr Opin Mol Ther. 2003;5(3):321–325.
63. Oldhoff JM, Darsow U, Werfel T, et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy. 2005;60(5):693–696.
64. Moosig F, Gross WL, Herrmann K, Bremer JP, Hellmich B. Targeting interleukin-5 in refractory and relapsing Churg–Strauss syndrome. Ann Intern Med. 2011;155:341–343.
65. 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):1336–1343.
66. Otani IM, Anilkumar AA, Newbury RO, et al. Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2013;131(6):1576–1582.
67. 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: 21–30.
68. Spergel JM, Rothenberg ME, Collins MH, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012;129: 456–463.
69. 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;128(5):989–995.
70. GlaxoSmithKline. Efficacy and Safety of Mepolizumab as an Add-On Treatment in Chronic Obstructive Pulmonary Disease (COPD); 2014. Available from: https://clinicaltrials.gov/ct2/show/NCT02105961. Accessed May 26, 2015. [NLM Identifier: NCT02105961].
71. McMaster University. Mepolizumab in Chronic Obstructive Pulmonary Diseases (COPD) with Eosinophilic Bronchitis; 2011. Available from: https://clinicaltrials.gov/ct2/show/NCT01463644. Accessed May 26, 2015. [NLM Identifier: NCT01463644].
72. Roufosse FE, Kahn JE, Gleich GJ, et al. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol. 2013;131(2):461–467.
73. Robinson DS. Mepolizumab treatment for asthma. Expert Opin Biol Ther. 2013;13(2):295–302.
74. Kikuchi S, Nagata M, Kikuchi I, Hagiwara K, Kanazawa M. Association between neutrophilic and eosinophilic inflammation in patients with severe persistent asthma. Int Arch Allergy Immunol. 2005;137(1): 7–11.
75. Menzella F, Facciolongo N, Piro R, et al. Clinical and pharmacoeconomic aspects of omalizumab: a 4-year follow-up. Ther Adv Respir Dis. 2012;6(2):87–95.
76. Cost a focus as GSK takes lead in new wave of biotech lung drugs. Reuters Edition UK. Mon September 8, 2014 1:45 pm BST. Available from: http://uk.reuters.com/article/2014/09/08/health-respiratory-gsk-idUKL5N0R921Y20140908. Accessed July 31, 2015.