Mepolizumab for eosinophilic severe asthma: Recent studies

Expert Opinion on Biological Therapy

Volumn 15, Issue 6, 2015, Pages 909-914

  Robinson, Douglas S ^a   Kariyawasam, Harsha H ^a  

^a UNIVERSITY COLLEGE LONDON HOSPITALS   (United Kingdom)

Author keywords

Asthma; Eosinophil; IL 5; Mepolizumab

Indexed keywords

BETA ADRENERGIC RECEPTOR STIMULATING AGENT; CORTICOSTEROID; INTERLEUKIN 5; INTERLEUKIN 5 MONOCLONAL ANTIBODY; MEPOLIZUMAB; MONOCLONAL ANTIBODY; PLACEBO; PREDNISONE; UNCLASSIFIED DRUG;

ARTICLE; ASTHMA; DRUG EFFICACY; DRUG INDICATION; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; EOSINOPHIL; EOSINOPHILIA; HUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); ANIMAL; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); IMMUNOLOGY; IMMUNOTHERAPY; PROCEDURES; SEVERITY OF ILLNESS INDEX; TRENDS;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; ASTHMA; CLINICAL TRIALS AS TOPIC; EOSINOPHILS; HUMANS; IMMUNOTHERAPY; INTERLEUKIN-5; SEVERITY OF ILLNESS INDEX;

EID: 84929856559     PISSN: 14712598     EISSN: 17447682     Source Type: Journal    
DOI: 10.1517/14712598.2015.1041911     Document Type: Article

References (28)

1. Menzies-Gow A, Robinson DS. Eosinophils, eosinophilic cytokines (interleukin-5), and antieosinophilic therapy in asthma. Curr Opin Pulm Med 2002;8:33-8
2. Kariyawasam HH, Robinson DS. The eosinophil: the cell and its weapons, the cytokines, its locations. Semin Respir Crit Care Med 2006;27:117-27
3. Green RH, Brightling CE, McKenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet 2002;360:1715-21
4. Coffman RL. Origins of the T(H)1-T (H)2 model: a personal perspective. Nat Immunol 2006;7:539-41
5. Robinson DS, Hamid Q, Ying S, et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 1992;326:298-304
6. Barlow JL, McKenzie AN. Type-2 innate lymphoid cells in human allergic disease. Curr Opin Allergy Clin Immunol 2014;14:397-403
7. Lee JJ, McGarry MP, Farmer SC, et al. Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J Exp Med 1997;185:2143-56
8. Foster PS, Hogan SP, Ramsay AJ, et al. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med 1996;183:195-201
9. Robinson DS, Ying S, Bentley AM, et al. Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. J Allergy Clin Immunol 1993;92:397-403
10. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43:343-73
11. Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008;178:218-24
12. Moore WC, Meyers DA, Wenzel SE, et al. National Heart, Lung, and Blood Institutes Severe Asthma Research Program. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010;181:315-23
13. 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;356:2144-8
14. Kips JC, OConnor BJ, Langley SJ, et al. Effect of SCH55700, a humanized antihuman interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med 2003;167:1655-9
15. Flood-Page P, Swenson C, Faiferman I, et al. International Mepolizumab Study Group. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 2007;176:1062-71
16. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. Eosinophils role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 2003;167:199-204
17. Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med 2009;180:388-95
18. Humbert M, Busse W, Hanania NA, et al. Omalizumab in asthma: an update on recent developments. J Allergy Clin Immunol Pract 2014;2:525-36
19. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-84
20. Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisonedependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-93
21. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380:651-9 . Large dose ranging study in asthmatics with unstable asthma and persistent airway eosinophilia. No dose response effect was seen but 50% reduction in exacerbation rates for all doses.
22. Ortega HG, Liu MC, Pavord ID, et al. MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014;371:1198-207
23. Bel EH, Wenzel SE, Thompson PJ, et al. SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014;371:1189-97
24. Bjermer L, Lemiere C, Maspero J, et al. A randomized phase 3 study of the efficacy and safety of reslizumab in subjects with asthma with elevated eosinophils. Eur Respir J 2014;44:Suppl 58
25. Castro M, Wenzel S, Kolbeck R, et al. A phase 2 study of benralizumab on exacerbations, lung function, and asthma control in adults with uncontrolled eosinophilic asthma. Eur Respir J 2014;44:Suppl 58
26. 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;128:989-95
27. Heaney LG, Robinson DS. Severe asthma treatment: need for characterising patients. Lancet 2005;365:974-6
28. Nair P. Anti-interleukin-5 monoclonal antibody to treat severe eosinophilic asthma. N Engl J Med 2014;371:1249-51