Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies

The Lancet Respiratory Medicine

Volumn 4, Issue 7, 2016, Pages 549-556

  Ortega, Hector G ^a   Yancey, Steven W ^a   Mayer, Bhabita ^b   Gunsoy, Necdet B ^b   Keene, Oliver N ^b   Bleecker, Eugene R ^c   Brightling, Christopher E ^d   Pavord, Ian D ^e  

^a GLAXOSMITHKLINE   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

^c WAKE FOREST SCHOOL OF MEDICINE   (United States)

^d GLENFIELD HOSPITAL   (United Kingdom)

^e UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

MEPOLIZUMAB; PLACEBO; ANTIASTHMATIC AGENT; MONOCLONAL ANTIBODY;

ADULT; AGED; ARTICLE; ASTHMA; CHILD; CONTROLLED STUDY; DISEASE COURSE; DISEASE EXACERBATION; DRUG EFFICACY; DRUG RESPONSE; EOSINOPHIL COUNT; FEMALE; FORCED EXPIRATORY VOLUME; HUMAN; LUNG FUNCTION; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; SCHOOL CHILD; TREATMENT DURATION; TREATMENT OUTCOME; VERY ELDERLY; ADOLESCENT; BLOOD; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFECTS; EOSINOPHIL; LEUKOCYTE COUNT; LOEFFLER PNEUMONIA; MIDDLE AGED; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANTI-ASTHMATIC AGENTS; ANTIBODIES, MONOCLONAL, HUMANIZED; ASTHMA; CHILD; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; EOSINOPHILS; FEMALE; HUMANS; LEUKOCYTE COUNT; MALE; MIDDLE AGED; PULMONARY EOSINOPHILIA; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84969941126     PISSN: 22132600     EISSN: 22132619     Source Type: Journal    
DOI: 10.1016/S2213-2600(16)30031-5     Document Type: Article

References (29)

1. 1 Wenzel, S, Severe asthma: from characteristics to phenotypes to endotypes. Clin Exp Allergy 42 (2012), 650–658.
2. 2 Chung, KF, Wenzel, SE, Brozek, JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 43 (2014), 343–373.
3. 3 Ortega, H, Katz, L, Gunsoy, N, Keene, O, Yancey, S, Blood eosinophil counts predict treatment response in patients with severe eosinophilic asthma. J Allergy Clin Immunol 136 (2015), 825–826.
4. 4 Fulkerson, PC, Rothenberg, ME, Targeting eosinophils in allergy, inflammation and beyond. Nat Rev Drug Discov 12 (2013), 117–129.
5. 5 Mukherjee, M, Sehmi, R, Nair, P, Anti-IL5 therapy for asthma and beyond. World Allergy Organ J, 7, 2014, 32.
6. 6 Green, RH, Brightling, CE, McKenna, S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet 360 (2002), 1715–1721.
7. 7 Nadif, R, Siroux, V, Oryszczyn, MP, et al. Heterogeneity of asthma according to blood inflammatory patterns. Thorax 64 (2009), 374–380.
8. 8 Pavord, ID, Korn, S, Howarth, P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 380 (2012), 651–659.
9. 9 Ortega, HG, Liu, MC, Pavord, ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 371 (2014), 1198–1207.
10. 10 Castro, M, Wenzel, SE, Bleecker, ER, 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 2 (2014), 879–890.
11. 11 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 3 (2015), 355–366.
12. 12 GlaxoSmithKline. Meta-analysis in sponsored studies MEA112997, MEA115588, and MEA115575 and a proof of concept investigator sponsored study CRT110184 of mepolizumab in severe asthma. http://www.gsk-clinicalstudyregister.com/study/204664?study_ids=204664#ps (accessed May 15, 2015).
13. 13 American Thoracic Society. Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. American Thoracic Society. Am J Respir Crit Care Med 162 (2000), 2341–2351.
14. 14 Reddel, HK, Taylor, DR, Bateman, ED, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 180 (2009), 59–99.
15. 15 Altman, DG, Royston, P, The cost of dichotomising continuous variables. BMJ, 332, 2006, 1080.
16. 16 Global Initiative for Asthma. Pocket guide for asthma management and prevention. http://www.ginasthma.org/wp-content/uploads/2016/01/GINA_Pocket_2015.pdf (accessed April 28, 2016).
17. 17 Ducharme, FM, Ni Chroinin, M, Greenstone, I, Lasserson, TJ, Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst Rev, 5, 2010 CD005535.
18. 18 Hanania, NA, Alpan, O, Hamilos, DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med 154 (2011), 573–582.
19. 19 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 60 (2005), 309–316.
20. 20 O'Neill, S, Sweeney, J, Patterson, CC, et al. The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry. Thorax 70 (2015), 376–378.
21. 21 Zeiger, RS, Schatz, M, Dalal, AA, et al. Utilization and costs of severe uncontrolled asthma in a managed-care setting. J Allergy Clin Immunol Pract 4 (2015), 120–129.
22. 22 O'Byrne, PM, Pedersen, S, Lamm, CJ, Tan, WC, Busse, WW, Severe exacerbations and decline in lung function in asthma. Am J Respir Crit Care Med 179 (2009), 19–24.
23. 23 Bel, EH, Wenzel, SE, Thompson, PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 371 (2014), 1189–1197.
24. 24 Amelink, M, de Groot, JC, de Nijs, SB, et al. Severe adult-onset asthma: A distinct phenotype. J Allergy Clin Immunol 132 (2013), 336–341.
25. 25 Price, DB, Rigazio, A, Campbell, JD, et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med 3 (2015), 849–858.
26. 26 Schleich, F, Brusselle, G, Louis, R, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir Med 108 (2014), 1723–1732.
27. 27 Zeiger, RS, Schatz, M, Li, Q, et al. High blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma. J Allergy Clin Immunol Pract 2 (2014), 741–750.
28. 28 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 133 (2014), 921–923.
29. 29 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 11 (2014), 531–536.