Effectiveness and safety of mepolizumab in treating eosinophilic asthma: a systematic review_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

JIANG Xunsheng , ZHOU Na , DONG Biwen , ZHANG Yanxia , KANG Qingxin , XI Huiming , DAI Lingli ,  JIAO Shenshan

Department of Respiratory Medicine, Nanchang Third Hospital, Nanchang, Jiangxi 330006, P. R. China;

Corresponding author：

JIAO Shenshan, Email: 15879110756@163.com

Keywords：

Mepolizumab; Anti-IL-5; Eosinophilic asthma; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1671-6205.201611032

Video：

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Objective To systematically evaluate the effectiveness and safety of mepolizumab in treating eosinophilic asthma. Methods Databases including PubMed, Embase, ISI Web of Science, Cochrane CENTRAL, MEDLINE, VIP and CNKI were searched to collect randomized controlled trials (RCTs) about mepolizumab for eosinophilic asthma from inception to October 2016. The references of these articles and relevant conference information were also manually retrieved. Meta-analysis was performed by RevMan 5.1 software after two researchers independently selected the literatures, extracted data and evaluated the quality according to the inclusion and exclusion criteria. Results A total of 9 RCTs involving 2273 patients were included. Compared with the control group, the acute exacerbation rate of asthma was decreased significantly in the mepolizumab treatment group [RR=0.67, 95%CI (0.53, 0.85), P=0.0009], eosinophil count in blood was significantly reduced [MD=–0.22, 95%CI (–0.29, –0.15), P<0.00001], eosinophil count in sputum was also significantly reduced [MD=–6.37, 95%CI (–9.68, –3.06), P<0.0002], and the proportion of patients with increased asthma-related quality of life (ACQ) score was higher significantly. The overall incidence of adverse reactions was similar between two groups [RR=0.90, 95%CI (0.71, 1.14), P=0.39]. The incidence of serious adverse reactions of mepolizumab treatment was superior to that of placebo [RR=0.45, 95%CI (0.23, 0.89), P=0.02]. The overall incidence of cardiovascular events was comparable between placebo and mepolizumab treatment [RR=0.95, 95%CI(0.40, 2.22), P=0.90]. Mepolizumab treatment may have a role in improving lung function, but the effect was not obvious. Conclusion Mepolizumab treatment can reduce the number of eosinophils in blood and sputum, reduce the exacerbation rate, and improve the quality of life of asthmatic patients with better safety.

Citation： JIANG Xunsheng, ZHOU Na, DONG Biwen, ZHANG Yanxia, KANG Qingxin, XI Huiming, DAI Lingli, JIAO Shenshan. Effectiveness and safety of mepolizumab in treating eosinophilic asthma: a systematic review. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(1): 6-14. doi: 10.7507/1671-6205.201611032 Copy

1.	Menzella F, Lusuardi M, Galeone C, et al. Tailored therapy for severe asthma. Multidiscip Respir Med, 2015, 10(1): 1-8.
2.	Schleich F, Brusselle G, Louis R, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir Med, 2014, 108(12): 1723-1732.
3.	Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet, 2012, 380(9842): 651-659.
4.	Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2013; 43(2): 343-73.
5.	Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008; 178(3): 218-224.
6.	Moore WC, Bleecker ER, Curraneverett D, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol, 2007, 119(2): 405-13.
7.	Custovic A, Johnston SL, Pavord I, et al. EAACI position statement on asthma exacerbations and severe asthma. Allergy, 2013, 68(12): 1520-1531.
8.	Global strategy for asthma management and prevention. 2016. Available at: http://ginasthma.org/2016-gina-report-global-strategy-for-asthma-management-and-preven tion/. Accessed May 31, 2016.
9.	Yancey SW, Ortega HG, Keene ON, et al. Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma. J Allergy Clin Immunol, 2016, 139(4): 1167-1175.
10.	Flood-Page PT, Menzies-Gow AN, Kay AB, et al. 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.
11.	Floodpage 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(11): 1062-71.
12.	Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med, 2009, 360(360): 973-984.
13.	Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone dependent asthma with sputum eosinophilia. N Engl J Med, 2009, 360(10): 985-993.
14.	Ayars AG, Altman LC, Potter-Perigo S, et al. Sputum hyaluronan and versican in severe eosinophilic asthma. Int Arch Allergy Immunol, 2013, 161(1): 65-73.
15.	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.
16.	Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med, 2014, 371(13): 1189-1197.
17.	Njira LN, Domingo C, Chanez P, et al. Long-term efficacy and safety of mepolizumab in patients with severe eosinophilic asthma: a multi-center, open-label, phase IIIb study. Clin Ther, 2016, 38 (9): 2058-2070.
18.	Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: http://www. cochrane-handbook.org.
19.	Wardlaw AJ, Brightling CE, Green R, et al. New insights into the relationship between airway inflammation and asthma. Clin Sci (Lond) 2002, 103: 201-211.
20.	Bousquet J, Chanez P, Lacoste J Y, et al. Eosinophilic inflammation in asthma. N Engl J Med, 1990, 323(15): 1033-9.
21.	Clutterbuck EJ, Hirst EM, Sanderson CJ. Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF. Blood, 1989, 73(6): 1504-12.
22.	Busse WW, Ring J, Hussmarp J, et al. A review of treatment with mepolizumab, an anti-IL-5 mAb, in hypereosinophilic syndromes and asthma. J Allergy Clin Immunol, 2010, 125(4): 803-13.
23.	Jayaram L, Pizzichini MM, Cook RJ, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J, 2006, 27(3): 483-94.
24.	Fitzgerald JM, Gibson PG. Asthma exacerbations. 4: Prevention. Thorax, 2006, 61(11): 992-9.
25.	Jatakanon A, Lim S, Barnes PJ. Changes in sputum eosinophils predict loss of asthma control. Am J Respir Crit Care Med, 2000, 161(1): 64-72.
26.	Deykin A, Lazarus SC, Fahy JV, et al. Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol, 2005, 115(4): 720-727.
27.	Green RH, Brightling CE, Mckenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet, 2003, 361(361): 1302-1303.

1. Menzella F, Lusuardi M, Galeone C, et al. Tailored therapy for severe asthma. Multidiscip Respir Med, 2015, 10(1): 1-8.
2. Schleich F, Brusselle G, Louis R, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir Med, 2014, 108(12): 1723-1732.
3. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet, 2012, 380(9842): 651-659.
4. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2013; 43(2): 343-73.
5. Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008; 178(3): 218-224.
6. Moore WC, Bleecker ER, Curraneverett D, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol, 2007, 119(2): 405-13.
7. Custovic A, Johnston SL, Pavord I, et al. EAACI position statement on asthma exacerbations and severe asthma. Allergy, 2013, 68(12): 1520-1531.
8. Global strategy for asthma management and prevention. 2016. Available at: http://ginasthma.org/2016-gina-report-global-strategy-for-asthma-management-and-preven tion/. Accessed May 31, 2016.
9. Yancey SW, Ortega HG, Keene ON, et al. Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma. J Allergy Clin Immunol, 2016, 139(4): 1167-1175.
10. Flood-Page PT, Menzies-Gow AN, Kay AB, et al. 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.
11. Floodpage 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(11): 1062-71.
12. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med, 2009, 360(360): 973-984.
13. Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone dependent asthma with sputum eosinophilia. N Engl J Med, 2009, 360(10): 985-993.
14. Ayars AG, Altman LC, Potter-Perigo S, et al. Sputum hyaluronan and versican in severe eosinophilic asthma. Int Arch Allergy Immunol, 2013, 161(1): 65-73.
15. 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.
16. Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med, 2014, 371(13): 1189-1197.
17. Njira LN, Domingo C, Chanez P, et al. Long-term efficacy and safety of mepolizumab in patients with severe eosinophilic asthma: a multi-center, open-label, phase IIIb study. Clin Ther, 2016, 38 (9): 2058-2070.
18. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: http://www. cochrane-handbook.org.
19. Wardlaw AJ, Brightling CE, Green R, et al. New insights into the relationship between airway inflammation and asthma. Clin Sci (Lond) 2002, 103: 201-211.
20. Bousquet J, Chanez P, Lacoste J Y, et al. Eosinophilic inflammation in asthma. N Engl J Med, 1990, 323(15): 1033-9.
21. Clutterbuck EJ, Hirst EM, Sanderson CJ. Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF. Blood, 1989, 73(6): 1504-12.
22. Busse WW, Ring J, Hussmarp J, et al. A review of treatment with mepolizumab, an anti-IL-5 mAb, in hypereosinophilic syndromes and asthma. J Allergy Clin Immunol, 2010, 125(4): 803-13.
23. Jayaram L, Pizzichini MM, Cook RJ, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J, 2006, 27(3): 483-94.
24. Fitzgerald JM, Gibson PG. Asthma exacerbations. 4: Prevention. Thorax, 2006, 61(11): 992-9.
25. Jatakanon A, Lim S, Barnes PJ. Changes in sputum eosinophils predict loss of asthma control. Am J Respir Crit Care Med, 2000, 161(1): 64-72.
26. Deykin A, Lazarus SC, Fahy JV, et al. Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol, 2005, 115(4): 720-727.
27. Green RH, Brightling CE, Mckenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet, 2003, 361(361): 1302-1303.

Chinese Journal of Respiratory and Critical Care Medicine

Effectiveness and safety of mepolizumab in treating eosinophilic asthma: a systematic review

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