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Anti-interleukin 5 Therapy for Eosinophilic Asthma: a Meta-analysis of Randomized Clinical Trials

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Abstract

Recently, more and more clinical trials have been performed to evaluate the effects of anti-interleukin (IL)-5 antibodies in eosinophilic asthma. However, a confirm conclusion has not been well established. We therefore sought to conduct a meta-analysis to assess the overall efficacy and safety of anti-interleukin 5 treatments in eosinophilic asthma. RCTs of anti-interleukin 5 treatments in eosinophilic asthma published up to June 2016 in PubMed, Embase, Cochrane library databases, and CBM, which reported pulmonary functions, quality-of-life scores, asthmatic exacerbations, and adverse events were included. Fixed-effect models were used to calculate mean difference, relative risks (RR), and 95 % CIs. Twelve studies involving 3340 patients were identified. Pooled analysis revealed significant improvements in FEV1 (nine trials, 1935 subjects; MD = 0.12; 95 % CI, 0.08–0.16), and Asthma Quality-of-Life Questionnaire scores (five trials, 1334 subjects; MD = 0.23; 95 % CI, 0.13–0.34). Anti-interleukin 5 treatment was also associated with significantly decreased exacerbation risk than placebo (six trials, 875 subjects; RR = 0.52; 95 % CI, 0.46 to 0.59) and a lower incidence of adverse events (eight trials, 1754 subjects; RR = 0.93; 95 % CI, 0.89 to 0.97). Anti-interleukin 5 treatment is well tolerated and could significantly improve FEV1, quality of life, and reduced exacerbations risk in patients with eosinophilic asthma. Further trials are necessary to assess the baseline blood eosinophil count to identify the optimal patients of eosinophilic asthma that could benefit from anti-interleukin 5 therapy.

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References

  1. Gibson PG (2009) Inflammatory phenotypes in adult asthma: clinical applications. Clin Respir J 3(4):198–206. doi:10.1111/j.1752-699X.2009.00162.x

    Article  PubMed  Google Scholar 

  2. Aleman F, Lim HF, Nair P (2016) Eosinophilic endotype of asthma. Immunol Allergy Clin North Am 36(3):559–568. doi:10.1016/j.iac.2016.03.006

    Article  PubMed  Google Scholar 

  3. Garcia G, Taille C, Laveneziana P, Bourdin A, Chanez P, Humbert M (2013) Anti-interleukin-5 therapy in severe asthma. Eur Respir Rev 22(129):251–257. doi:10.1183/09059180.00004013

    Article  PubMed  Google Scholar 

  4. Durham AL, Caramori G, Chung KF, Adcock IM (2016) Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease. Transl Res 167(1):192–203. doi:10.1016/j.trsl.2015.08.004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Takatsu K, Nakajima H (2008) IL-5 and eosinophilia. Curr Opin Immunol 20(3):288–294. doi:10.1016/j.coi.2008.04.001

    Article  PubMed  CAS  Google Scholar 

  6. Flood-Page P, Swenson C, Faiferman I, Matthews J, Williams M, Brannick L, Robinson D, Wenzel S, Busse W, Hansel TT, Barnes NC (2007) A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 176(11):1062–1071

    Article  PubMed  CAS  Google Scholar 

  7. Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, WardIaw AJ, Pavord ID (2009) Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 360(10):973–984

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Nair P, Pizzichini MMM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O’Byrne PM (2009) Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 360(10):985–993

    Article  PubMed  CAS  Google Scholar 

  9. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID (2014) Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 371(13):1189–1197. doi:10.1056/NEJMoa1403291

    Article  PubMed  CAS  Google Scholar 

  10. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P, Investigators M (2014) Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 371(13):1198–1207

    Article  PubMed  CAS  Google Scholar 

  11. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P (2012) Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet (London, England) 380(9842):651–659. doi:10.1016/s0140-6736(12)60988-x

    Article  CAS  Google Scholar 

  12. Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW, Gossage DL, Ward CK, Wu Y, Wang B, Khatry DB, Merwe R, Kolbeck R, Molfino NA, Raible DG (2014) 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(11):878–890. doi:10.1016/S2213-2600%2814%2970201-2

    Article  Google Scholar 

  13. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62(10):1006–1012. doi:10.1016/j.jclinepi.2009.06.005

    Article  PubMed  Google Scholar 

  14. Higgins J, Green S (2013) Cochrane handbook for systematic reviews of interventions version 5.1. 0, The Cochrane Collaboration, 2011

    Google Scholar 

  15. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. doi:10.1002/sim.1186

    Article  PubMed  Google Scholar 

  16. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed) 315(7109):629–634

    Article  CAS  Google Scholar 

  17. Brok J, Thorlund K, Wetterslev J, Gluud C (2009) Apparently conclusive meta-analyses may be inconclusive—trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. Int J Epidemiol 38(1):287–298

    Article  PubMed  Google Scholar 

  18. Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C (2011) User manual for trial sequential analysis (TSA). Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen

    Google Scholar 

  19. Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, Wilkins HJ, Henkel T, Nair P (2011) Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 184(10):1125–1132. doi:10.1164/rccm.201103-0396OC

    Article  PubMed  CAS  Google Scholar 

  20. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P (2015) 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(5):355–366. doi:10.1016/S2213-2600(15)00042-9

    Article  PubMed  CAS  Google Scholar 

  21. Corren J, Weinstein S, Janka L, Zangrilli J, Garin M (2016) Phase 3 study of reslizumab in patients with poorly controlled asthma: effects across a broad range of eosinophil counts. Chest. doi:10.1016/j.chest.2016.03.018

    Article  PubMed  Google Scholar 

  22. Bjermer L, Lemiere C, Maspero J, Weiss S, Zangrilli J, Germinaro M (2016) Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: a randomized phase 3 study. Chest. doi:10.1016/j.chest.2016.03.032

    Article  PubMed  Google Scholar 

  23. Laviolette M, Gossage DL, Gauvreau G, Leigh R, Olivenstein R, Katial R, Busse WW, Wenzel S, Wu Y, Datta V, Kolbeck R, Molfino NA (2013) Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol 132(5):1086–1096.e1085. doi:10.1016/j.jaci.2013.05.020

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Park HS, Kim MK, Imai N, Nakanishi T, Adachi M, Ohta K (2016) A phase 2a study of benralizumab for patients with eosinophilic asthma in South Korea and Japan. Int Arch Allergy Immunol 169(3):135–145. doi:10.1159/000444799

    Article  PubMed  CAS  Google Scholar 

  25. The Global Asthma Report (2014) Auckland. Global Asthma Network, New Zealand, Available at: http://www.globalasthmareport.org/resources/Global_Asthma_Report_2014.pdf

    Google Scholar 

  26. Cardet JC, Israel E (2015) Update on reslizumab for eosinophilic asthma. Expert Opin Biol Ther 15(10):1531–1539. doi:10.1517/14712598.2015.1090972

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Liu Y, Zhang S, Li DW, Jiang SJ (2013) Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials. PLoS One 8:3. doi:10.1371/journal.pone.0059872

    Article  CAS  Google Scholar 

  28. Powell C, Milan SJ, Dwan K, Bax L, Walters N (2015) Mepolizumab versus placebo for asthma. Cochrane Database Syst Rev 7:CD010834

    Google Scholar 

  29. Leckie MJ, Ten Brinke A, Khan J, Diamant Z, O’Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ (2000) Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet (London, England) 356(SUPPL):2144–2148

    Article  CAS  Google Scholar 

  30. Juniper EF, Guyatt G, Epstein R, Ferrie P, Jaeschke R, Hiller TK (1992) Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax 47(2):76–83

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Juniper EF, Guyatt GH, Willan A, Griffith LE (1994) Determining a minimal important change in a disease-specific Quality of Life Questionnaire. J Clin Epidemiol 47(1):81–87

    Article  PubMed  CAS  Google Scholar 

  32. Masoli M, Fabian D, Holt S, Beasley R, Global Initiative for Asthma P (2004) The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59(5):469–478. doi:10.1111/j.1398-9995.2004.00526.x

    Article  PubMed  Google Scholar 

  33. Schatz M, Li Q, Chen W, Khatry D, Tran T, Zeiger R (2014) Elevated blood eosinophil level is a risk factor for exacerbations in adult persistent asthma. In: C33. Cytokines and asthma mediators. Am Thoracic Soc A4235–A4235

  34. Malinovschi A, Fonseca JA, Jacinto T, Alving K, Janson C (2013) Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects. The Journal of Allergy and Clinical Immunology 132 (4):821–827 e821–825. doi:10.1016/j.jaci.2013.06.007

  35. Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID (2002) Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet (London, England) 360(9347):1715–1721. doi:10.1016/S0140-6736(02)11679-5

    Article  Google Scholar 

  36. Nadif R, Siroux V, Oryszczyn MP, Ravault C, Pison C, Pin I, Epidemiological Study on the Genetics and Environment of Asthma (EGEA) (2009) Heterogeneity of asthma according to blood inflammatory patterns. Thorax 64(5):374–380. doi:10.1136/thx.2008.103069

    Article  PubMed  CAS  Google Scholar 

  37. Ortega HG, Yancey SW, Mayer B, Gunsoy NB, Keene ON, Bleecker ER, Brightling CE, Pavord ID (2016) Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respir Med 4(7):549–556. doi:10.1016/S2213-2600(16)30031-5

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We are grateful to the authors of the primary studies included in this meta-analysis. We thank Jiao-Qing Tang for his help and editorial advice during the preparation of the review.

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    Authors and Affiliations

    1. Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China

      Fa-Ping Wang, Xiao-Feng Xiong, Ting Liu, De-Yun Cheng & Hui Mao

    2. Department of Respiratory Medicine, First Affiliated Hospital of Henan College of Traditional Chinese Medicine, Zhengzhou, 450000, China

      Su-Yun Li

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    This study did not receive any funding.

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    Author Contributions

    Fa-Ping Wang and Xiao-Feng Xiong performed the literature searches, selected the studies, analyzed the data, and wrote the manuscript draft. Ting Liu and Su-Yun Li aided in the data analysis. Hui Mao and De-Yun Cheng designed the study and revised manuscript.

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    This article does not contain any studies with human participants or animals performed by any of the authors.

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    Fa-Ping Wang and Xiao-Feng Xiong contributed equally to this work.

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    Wang, FP., Xiong, XF., Liu, T. et al. Anti-interleukin 5 Therapy for Eosinophilic Asthma: a Meta-analysis of Randomized Clinical Trials. Clinic Rev Allerg Immunol 54, 318–330 (2018). https://doi.org/10.1007/s12016-016-8588-x

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