Advertisement

Frontiers of Medicine

, Volume 12, Issue 3, pp 340–349 | Cite as

Efficacy and safety of benralizumab in patients with eosinophilic asthma: a meta-analysis of randomized placebo-controlled trials

  • Ting Liu
  • Faping Wang
  • Geng Wang
  • Hui MaoEmail author
Letter to Frontiers of Medicine

Abstract

Benralizumab is a monoclonal antibody that targets interleukin-5 receptor α to deplete blood eosinophils and improve the clinical outcomes of allergic asthma. We conducted a meta-analysis to evaluate the safety and efficacy of different doses of benralizumab in patients with eosinophilic asthma. All randomized controlled trials involving benralizumab treatment for patients with eosinophilic asthma, which were searched in PubMed, Embase, and the Cochrane Library published until January 2017, as well as the rate of asthmatic exacerbation, pulmonary functionality, asthma control, quality of life scores, and adverse events were included. Randomized-effect models were used in the meta-analysis to calculate the pooled mean difference, relative risks, and 95% confidence intervals. Five studies involving 1951 patients were identified. Compared with the placebo, benralizumab treatment demonstrated significant improvements in the forced expiratory volume in 1 s (FEV1), Asthma Quality of Life Questionnaire scores, decreased asthmatic exacerbation and Asthma Control Questionnaire-6 (ACQ-6) scores. Benralizumab treatment was also not associated with increased adverse events. These findings indicated that benralizumab can be safely used to improve FEV1, enhance patient symptom control and quality of life, and reduce the risk of exacerbations and ACQ-6 scores in patients with eosinophilic asthma. Furthermore, our meta-analysis showed that benralizumab with 30 mg (every eight weeks) dosage can improve the health-related quality of life and appear to be more effective than 30 mg (every four weeks) dosage. Overall, data indicated that the optimal dosing regimen for benralizumab was possibly 30 mg (every eight weeks).

Keywords

benralizumab anti-interleukin-5 monoclonal antibody eosinophilic asthma meta-analysis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Global Asthma Network. The Global Asthma Report 2014. Auckland, New Zealand: Global Asthma Network, 2014. Available: http://www.globalasthmareport.org/resources/Global_Asthma_Report_2014.pdfGoogle Scholar
  2. 2.
    McIvor RA. Emerging therapeutic options for the treatment of patients with symptomatic asthma. Ann Allergy Asthma Immunol 2015; 115(4): 265–271.e5CrossRefPubMedGoogle Scholar
  3. 3.
    Torrego A, Solà I, Munoz AM, Roqué I Figuls M, Yepes-Nuñez JJ, Alonso-Coello P, Plaza V. Bronchial thermoplasty for moderate or severe persistent asthma in adults. Cochrane Database Syst Rev 2014; (3): CD009910Google Scholar
  4. 4.
    Chung KF. Targeting the interleukin pathway in the treatment of asthma. Lancet 2015; 386(9998): 1086–1096CrossRefPubMedGoogle Scholar
  5. 5.
    Mitchell PD, El-Gammal AI, O’Byrne PM. Emerging monoclonal antibodies as targeted innovative therapeutic approaches to asthma. Clin Pharmacol Ther 2016; 99(1): 38–48CrossRefPubMedGoogle Scholar
  6. 6.
    Aleman F, Lim HF, Nair P. Eosinophilic endotype of asthma. Immunol Allergy Clin North Am 2016; 36(3): 559–568CrossRefPubMedGoogle Scholar
  7. 7.
    Cardet JC, Israel E. Update on reslizumab for eosinophilic asthma. Expert Opin Biol Ther 2015; 15(10): 1531–1539CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Khorasanizadeh M, Eskian M, Assa’ad AH, Camargo CA Jr, Rezaei N. Efficacy and safety of benralizumab, a monoclonal antibody against IL-5Ra, in uncontrolled eosinophilic asthma. Int Rev Immunol 2016; 35(4): 294–311CrossRefPubMedGoogle Scholar
  9. 9.
    Wu Y, Li JJ, Kim HJ, Liu X, Liu W, Akhgar A, Bowen MA, Spitz S, Jiang XR, Roskos LK, White WI. A neutralizing antibody assay based on a reporter of antibody-dependent cell-mediated cytotoxicity. AAPS J 2015; 17(6): 1417–1426CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012; 380(9842): 651–659CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371(13): 1189–1197CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ortega HG, Liu MC, Pavord ID, Brusselle GG, Fitz Gerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P; MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014; 371(13): 1198–1207CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, Murphy K, Maspero JF, O’Brien C, Korn S. 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): 355–366CrossRefPubMedGoogle Scholar
  14. 14.
    Bleecker ER, Fitz Gerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkström V, Goldman M; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting ß2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016; 388(10056): 2115–2127CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ghazi A, Trikha A, Calhoun WJ. Benralizumab—a humanized mAb to IL-5Ra with enhanced antibody-dependent cell-mediated cytotoxicity—a novel approach for the treatment of asthma. Expert Opin Biol Ther 2012; 12(1): 113–118CrossRefPubMedGoogle Scholar
  16. 16.
    Busse WW, Katial R, Gossage D, Sari S, Wang B, Kolbeck R, Coyle AJ, Koike M, Spitalny GL, Kiener PA, Geba GP, Molfino NA. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol 2010; 125(6): 1237–1244.e2CrossRefPubMedGoogle Scholar
  17. 17.
    Menzella F, Lusuardi M, Galeone C, Facciolongo N, Zucchi L. The clinical profile of benralizumab in the management of severe eosinophilic asthma. Ther Adv Respir Dis 2016; 10(6): 534–548CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Higgins J, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1. 0. The Cochrane Collaboration, 2011Google Scholar
  19. 19.
    Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557–560CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Laviolette M, Gossage DL, Gauvreau G, Leigh R, Olivenstein R, Katial R, Busse WW, Wenzel S, Wu Y, Datta V, Kolbeck R, Molfino NA. Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol 2013; 132(5): 1086–1096.e5CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW, Gossage DL, Ward CK, Wu Y, Wang B, Khatry DB, van der Merwe R, Kolbeck R, Molfino NA, Raible DG. Benralizumab, an anti-interleukin 5 receptor a monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised doseranging study. Lancet Respir Med 2014; 2(11): 879–890CrossRefPubMedGoogle Scholar
  23. 23.
    Park HS, Kim MK, Imai N, Nakanishi T, Adachi M, Ohta K, Tohda Y; Asian Benralizumab Study Group. A phase 2a study of benralizumab for patients with eosinophilic asthma in South Korea and Japan. Int Arch Allergy Immunol 2016; 169(3): 135–145CrossRefPubMedGoogle Scholar
  24. 24.
    Fitz Gerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, Busse WW, Barker P, Sproule S, Gilmartin G, Werkström V, Aurivillius M, Goldman M; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor a monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2016; 388 (10056): 2128–2141CrossRefGoogle Scholar
  25. 25.
    Hilvering B, Xue L, Pavord ID. 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): 135–145CrossRefPubMedGoogle Scholar
  26. 26.
    Rudulier CD, Larché M, Moldaver D. Treatment with anti-cytokine monoclonal antibodies can potentiate the target cytokine rather than neutralize its activity. Allergy 2016; 71(3): 283–285CrossRefPubMedGoogle Scholar
  27. 27.
    Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med 2016; 111: 21–29CrossRefPubMedGoogle Scholar
  28. 28.
    Ortega HG, Yancey SW, Mayer B, Gunsoy NB, Keene ON, Bleecker ER, Brightling CE, Pavord ID. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respir Med 2016; 4(7): 549–556CrossRefPubMedGoogle Scholar
  29. 29.
    Cabon Y, Molinari N, Marin G, Vachier I, Gamez AS, Chanez P, Bourdin A. Comparison of anti-interleukin-5 therapies in patients with severe asthma: global and indirect meta-analyses of randomized placebo-controlled trials. Clin Exp Allergy 2017; 47(1): 129–138CrossRefPubMedGoogle Scholar
  30. 30.
    Wang B, Yan L, Hutmacher M, White W, Ward CK, Nielsen J, Wu Y, Goldman M, Raible DG, Roskos L. Exposure-response analysis for determination of benralizumab optimal dosing regimen in adults with asthma. Am J Respir Crit Care Med 2014; 189: A1324Google Scholar
  31. 31.
    Juniper EF, Guyatt GH, Willan A, Griffith LE. Determining a minimal important change in a disease-specific Quality of Life Questionnaire. J Clin Epidemiol 1994; 47(1): 81–87CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Respiratory Medicine, West China HospitalSichuan UniversityChengduChina

Personalised recommendations