Mepolizumab for the reduction of exacerbations in severe eosinophilic asthma

Expert Review of Respiratory Medicine

Volumn 10, Issue 6, 2016, Pages 607-617

  Russell, Richard ^a   Brightling, Christopher ^a  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

asthma; eosinophils; exacerbation; interleukin 5; Mepolizumab

Indexed keywords

ALLERGEN; BENRALIZUMAB; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; CORTICOSTEROID; DUPILUMAB; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 5; LEBRIKIZUMAB; LEUKOTRIENE RECEPTOR BLOCKING AGENT; LONG ACTING DRUG; MACROLIDE; MEPOLIZUMAB; MUSCARINIC RECEPTOR BLOCKING AGENT; OMALIZUMAB; RESLIZUMAB; THEOPHYLLINE; TRALOKINUMAB; TRANSCRIPTION FACTOR RUNX2; MONOCLONAL ANTIBODY;

AIRWAY REMODELING; ARTICLE; ASTHMA; BACKACHE; BRONCHIAL THERMOPLASTY; BRONCHITIS; CORTICOSTEROID THERAPY; CROSSOVER PROCEDURE; DISEASE EXACERBATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG APPROVAL; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EOSINOPHIL COUNT; EOSINOPHILIA; EOSINOPHILIC ASTHMA; FORCED EXPIRATORY VOLUME; HEADACHE; HUMAN; IMMUNOGENICITY; IMMUNOSUPPRESSIVE TREATMENT; IMMUNOTHERAPY; INJECTION SITE REACTION; INJURY; LONG TERM CARE; LUNG FUNCTION; MACULOPAPULAR RASH; MONOTHERAPY; NAUSEA; OXIDATIVE STRESS; PEAK EXPIRATORY FLOW; PHARYNGITIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN TARGETING; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESPIRATORY TRACT ALLERGY; RESPIRATORY TRACT INFLAMMATION; RHINITIS; RHINOPHARYNGITIS; SINUSITIS; SYSTEMATIC REVIEW (TOPIC); UPPER RESPIRATORY TRACT INFECTION; VIRUS INFECTION; COMPLICATION;

ANTIBODIES, MONOCLONAL, HUMANIZED; ASTHMA; EOSINOPHILIA; HUMANS;

EID: 84965020876     PISSN: 17476348     EISSN: 17476356     Source Type: Journal    
DOI: 10.1080/17476348.2016.1176532     Document Type: Article

References (78)

1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention [Internet]. 2015. [cited 2015 Nov 23]. Available from: http://www.ginasthma.org
2. J.Bousquet, E.Mantzouranis, A.A.Cruz, et al. Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization consultation on severe asthma. J Allergy Clin Immunol. 2010;126(5):926–938.
3. World Health Organisation. The global burden of disease: 2004 update. Geneva: WHO Press; 2004.
4. R.Lozano, M.Naghavi, K.Foreman, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380(9859):2095–2128.
5. Royal College of Physicians. Why asthma still kills: the National Review of Asthma Deaths (NRAD) confidential enquiry report. London: RCP; 2014.
6. D.R.Taylor, E.D.Bateman, L.-P.Boulet, et al. A new perspective on concepts of asthma severity and control. Eur Respir J. 2008;32(3):545–554.• Outlines current concepts of asthma severity and control.
7. National Heart, Lung and Blood Institute. National asthma education and prevention program, expert panel report 3: guidelines for the diagnosis and management of asthma [Internet]. 2007. [cited 2015 Nov 23]. Available from: http://www.nhlbi.nih.gov
8. British Thoracic Society/Scottish Intercollegiate Network. British guideline on the management of asthma. Thorax. 2014. [cited 69 Suppl 1]; i1-i192]. Available from: https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-2014/
9. K.F.Chung, S.E.Wenzel, J.L.Brozek, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343–373.• Provides consensus definitions and guidelines specifically related to severe asthma assessment and management.
10. P.J.Barnes Severe asthma: advances in current management and future therapy. J Allergy Clin Immunol. 2012;129(1):48–59.
11. S.E.Wenzel. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716–725.
12. R.H.Green, C.E.Brightling, G.Woltmann, et al. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax. 2002;57(10):875–879.
13. K.W.McGrath, N.Icitovic, H.A.Boushey, et al. A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med. 2012;185(6):612–619.
14. Choy DF, Hart KM, Borthwick LA, et al. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. Sci Transl Med. 2015;7(301):301ra129.
15. B.Thomas, A.Rutman, R.A.Hirst, et al. Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma. J Allergy Clin Immunol. 2010;126(4):722–729.e2.
16. R.Berair, C.E.Brightling. Asthma therapy and its effect on airway remodelling. Drugs. 2014;74(12):1345–1369.
17. A.Sutcliffe, F.Hollins, E.Gomez, et al. Increased nicotinamide adenine dinucleotide phosphate oxidase 4 expression mediates intrinsic airway smooth muscle hypercontractility in asthma. Am J Respir Crit Care Med. 2012;185(3):267–274.
18. J.Douwes, P.Gibson, J.Pekkanen, et al. Non-eosinophilic asthma: importance and possible mechanisms. Thorax. 2002;57(7):643–648.
19. O.Eltboli, C.E.Brightling. Eosinophils as diagnostic tools in chronic lung disease. Expert Rev Respir Med. 2013;7(1):33–42.
20. M.Boorsma, R.Lutter, M.A.van de Pol, et al. Repeatability of inflammatory parameters in induced sputum of COPD patients. COPD. 2007;4(4):321–329.
21. E.Pizzichini, M.M.Pizzichini, A.Efthimiadis, et al. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996;154(2 Pt 1):308–317.
22. A.Jatakanon, S.Lim, P.J.Barnes. Changes in sputum eosinophils predict loss of asthma control. Am J Respir Crit Care Med. 2000;161(1):64–72.
23. N.A.Hanania, M.Noonan, J.Corren, et al. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax. 2015;70(8):748–756.• Confirmed periostin as a reliable biomarker for interleukin-13 activity and central trial in lebrikizumab development.
24. J.Sweeney, C.E.Brightling, A.Menzies-Gow, et al. Clinical management and outcome of refractory asthma in the UK from the British thoracic society difficult asthma registry. Thorax. 2012;67(8):754–756.
25. A.ten Brinke, A.H.Zwinderman, P.J.Sterk, et al. “Refractory” eosinophilic airway inflammation in severe asthma: effect of parenteral corticosteroids. Am J Respir Crit Care Med. 2004;170(6):601–605.
26. L.Mancinelli, L.Navarro, O.P.Sharma. Intramuscular high-dose triamcinolone acetonide in the treatment of severe chronic asthma. West J Med. 1997;167(5):322–329.
27. I.D.Pavord, C.E.Brightling, G.Woltmann, et al. Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999;353(9171):2213–2214.
28. C.E.Brightling, W.Monteiro, R.Ward, et al. Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2000;356(9240):1480–1485.
29. M.R.Pratter, C.E.Brightling, L.P.Boulet, et al. An empiric integrative approach to the management of cough: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):222s–231s.
30. R.H.Green, C.E.Brightling, S.McKenna, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002;360(9347):1715–1721.• Pivotal study showing the importance of managing eosinophilic inflammation to reduce exacerbations.
31. J.Chlumsky, I.Striz, M.Terl, et al. Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma. J Int Med Res. 2006;34(2):129–139.
32. L.Jayaram, M.M.Pizzichini, R.J.Cook, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J. 2006;27(3):483–494.
33. H.L.Petsky, C.J.Cates, T.J.Lasserson, et al. A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils). Thorax. 2012;67(3):199–208.
34. R.H.Green, C.E.Brightling, S.McKenna, et al. Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness. Eur Respir J. 2006;27(6):1144–1151.
35. H.A.Kerstjens, M.Engel, R.Dahl, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012;367(13):1198–1207.
36. D.E.Anderson, K.M.Kew, A.C.Boyter. Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus the same dose of ICS alone for adults with asthma. Cochrane Database Syst Rev. 2015;8:CD011397.
37. M.Miligkos, R.R.Bannuru, H.Alkofide, et al. Leukotriene-receptor antagonists versus placebo in the treatment of asthma in adults and adolescents: a systematic review and meta-analysis. Ann Intern Med. 2015;163(10):756–767.
38. F.M.Ducharme. Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma. Cochrane Database Syst Rev. 2004;(1):CD003133.
39. H.Nie, G.Zhang, M.Liu, et al. Efficacy of theophylline plus salmeterol/fluticasone propionate combination therapy in patients with asthma. Respir Med. 2013;107(3):347–354.
40. R.Normansell, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;1:CD003559.
41. C.Gouder, L.M.West, S.Montefort. The real-life clinical effects of 52 weeks of omalizumab therapy for severe persistent allergic asthma. Int J Clin Pharm. 2015;37(1):36–43.
42. T.Tajiri, A.Niimi, H.Matsumoto, et al. Comprehensive efficacy of omalizumab for severe refractory asthma: a time-series observational study. Ann Allergy Asthma Immunol. 2014;113(4):470–475.e2.
43. R.Djukanovic, S.J.Wilson, M.Kraft, et al. Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med. 2004;170(6):583–593.
44. N.A.Hanania, S.Wenzel, K.Rosén, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med. 2013;187(8):804–811.• Important study linking biomarkers to anti-IgE therapy responder groups.
45. A.Woodcock, L.Forster, E.Matthews, et al. Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma. N Engl J Med. 2003;349(3):225–236.
46. R.Normansell, K.M.Kew, A.L.Bridgman. Sublingual immunotherapy for asthma. Cochrane Database Syst Rev. 2015;8:CD011293.
47. R.J.Boyle, C.Pedroletti, M.Wickman, et al. Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial. Thorax. 2012;67(3):215–221.
48. K.M.Kew, Undela K, Kotortsi I, et al. Macrolides for chronic asthma. Cochrane Database Syst Rev. 2015;9:Cd002997.
49. G.G.Brusselle, C.Vanderstichele, P.Jordens, et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax. 2013;68(4):322–329.
50. A.G.Alexander, N.C.Barnes, A.B.Kay. Trial of cyclosporin in corticosteroid-dependent chronic severe asthma. Lancet. 1992;339(8789):324–328.
51. D.J.Evans, P.Cullinan, D.M.Geddes, et al. Cyclosporin as an oral corticosteroid sparing agent in stable asthma. Cochrane Database Syst Rev. 2001;(4):CD002993.
52. H.Davies, L.Olson, P.Gibson. Methotrexate as a steroid sparing agent for asthma in adults. Cochrane Database Syst Rev. 2000;(3):CD000391.
53. I.D.Pavord, G.Cox, N.C.Thomson, et al. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. Am J Respir Crit Care Med. 2007;176(12):1185–1191.
54. M.Castro, A.S.Rubin, M.Laviolette, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med. 2010;181(2):116–124.• Important study in determining effect of bronchial thermoplasty – a nonpharmaceutical treatment pathway for severe asthma.
55. M.E.Wechsler, M.Laviolette, A.S.Rubin, et al. Bronchial thermoplasty: long-term safety and effectiveness in patients with severe persistent asthma. J Allergy Clin Immunol. 2013;132(6):1295–1302.
56. B.Hilvering, L.Xue, I.D.Pavord. Evidence for the efficacy and safety of anti-interleukin-5 treatment in the management of refractory eosinophilic asthma. Ther Adv Respir Dis. 2015;9(4):135–145.
57. P.Flood-Page, C.Swenson, I.Faiferman, 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):1062–1071.•• Pivotal study in development of mepolizumab.
58. P.Haldar, C.E.Brightling, B.Hargadon, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360(10):973–984.•• Pivotal study in development of mepolizumab.
59. P.Nair, M.M.M.Pizzichini, M.Kjarsgaard, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360(10):985–993.•• Pivotal study in development of mepolizumab.
60. I.D.Pavord, S.Korn, P.Howarth, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651–659.•• Pivotal study in development of mepolizumab.
61. H.G.Ortega, M.C.Liu, I.D.Pavord, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198–1207.•• Pivotal study in development of mepolizumab.
62. E.H.Bel, S.E.Wenzel, P.J.Thompson, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189–1197.•• Pivotal study in development of mepolizumab.
63. P.Haldar, C.E.Brightling, A.Singapuri, 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.•• Pivotal study in development of mepolizumab.
64. Teva Pharmaceutical Industries Research Pipeline. 2015 [cited 2015 Nov27]. Available from: http://www.tevapharm.com/research_development/rd_focus/pipeline/
65. M.Castro, J.Zangrilli, M.E.Wechsler, 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.• Central trial in reslizumab development – a competitor agent to mepolizumab.
66. M.Castro, S.E.Wenzel, E.R.Bleecker, et al. 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):879–890.• Central trial in benralizumab development – a competitor agent to mepolizumab.
67. R.M.Nowak, J.M.Parker, R.A.Silverman, et al. A randomized trial of benralizumab, an antiinterleukin 5 receptor alpha monoclonal antibody, after acute asthma. Am J Emerg Med. 2015;33(1):14–20.• Central trial in reslizumab development – a competitor agent to mepolizumab.
68. ClinicalTrials.gov Clinical Studies Registry. 2015 [cited 2015 Nov27]. Available from: https://clinicaltrials.gov/
69. C.E.Brightling, P.Chanez, R.Leigh, et al. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015;3(9):692–701.• Central trial in tralokinumab development – a competitor agent to mepolizumab.
70. A.Vatrella, I.Fabozzi, C.Calabrese, et al. Dupilumab: a novel treatment for asthma. J Asthma Allergy. 2014;7:123–130.
71. S.Wenzel, L.Ford, D.Pearlman, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368(26):2455–2466.• Central trial in dupilumab development – a competitor agent to mepolizumab.
72. R.Berair, S.Gonem, A.Singapuri, et al. Effect of QAW039, an oral prostaglandin D2 receptor (DP2/CRTH2) antagonist, upon sputum and bronchial eosinophilic inflammation and clinical outcomes in treatment-resistant asthma: a phase 2a randomized placebo-controlled trial. Eur Respir J. 2015;46(Suppl. 59):OA290.• Central trial in anti-CRTH2 development.
73. S.Gonem, Berair R, Singapuri A, et al. Late-breaking abstract: phase 2a randomized placebo-controlled trial of the oral prostaglandin D2 receptor (DP2/CRTh2) antagonist QAW039 in eosinophilic asthma. Eur Respir J. 2014;44(Suppl. 58):2908• Central trial in anti-CRTH2 development.
74. U.S. Food and Drug Administration. [cited 2016 Mar 9]. Available from: http://www.fda.gov
75. European Medicines Agency. [cited 2016 Mar 9]. Available from: http://www.ema.europa.eu
76. UK Medicines Information. [cited 2016 Mar 9]. Available from: http://www.ukmi.nhs.uk/
77. GlaxoSmithKline 2015 Quarter 2 Press Release. [cited 2015 Sep 24]. Available from: https://www.gsk.com/en-gb/media
78. C.Powell, S.J.Milan, K.Dwan, et al. Mepolizumab versus placebo for asthma. Cochrane Database Syst Rev. 2015;7:CD010834.•• Cochrane review of current mepolizumab trial evidence.