Login Register Cart 0
Generic placeholder image

Current Respiratory Medicine Reviews

Editor-in-Chief

ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Novel Biologics for the Treatment of Pediatric Severe Asthma

Author(s): Amelia Licari, Riccardo Castagnoli, Enrico Tondina, Giorgia Testa, Giuseppe Fabio Parisi, Alessia Marseglia, Ilaria Brambilla and Gian Luigi Marseglia*

Volume 15, Issue 3, 2019

Page: [195 - 204] Pages: 10

DOI: 10.2174/1573398X15666190521111816

Abstract

Estimated to represent less than 5% of all asthmatic patients, children with severe asthma experience troublesome persistent symptoms, life-threatening attacks and side effects by oral corticosteroid treatment, that significantly impact on the quality of life and on economic costs. An accurate understanding of the mechanisms of the disease has been crucial for the discovery and development of biological therapies, for which children with severe asthma are candidates. The aim of this review is to discuss the use of approved biologics for severe asthma, providing updated evidence of novel targeted therapies in the pediatric age range.

Keywords: Benralizumab, children, dupilumab, mepolizumab, omalizumab, reslizumab, severe asthma.

« Previous Next »
Graphical Abstract

[1]
Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014; 43(2): 343-73.
[http://dx.doi.org/10.1183/09031936.00202013] [PMID: 24337046]
[2]
Global Initiative for Asthma GINA guidelines Global strategy for Asthma Management and Prevention Available at. www.gin asthma.org
[3]
Chipps BE, Parikh NG, Maharaj SK. Severe Asthma in Children. Curr Allergy Asthma Rep 2017; 17(4): 21.
[http://dx.doi.org/10.1007/s11882-017-0688-z] [PMID: 28353215]
[4]
Licari A, Marseglia GL. Current and future challenges in pediatric severe asthma. Curr Med Res Opin 2018; 34(5): 943-4.
[http://dx.doi.org/10.1080/03007995.2018.1439463] [PMID: 29421950]
[5]
Bush A, Fleming L, Saglani S. Severe asthma in children. Respirology 2017; 22(5): 886-97.
[http://dx.doi.org/10.1111/resp.13085] [PMID: 28543931]
[6]
Licari A, Brambilla I, Marseglia A, De Filippo M, Paganelli V, Marseglia GL. Difficult vs. severe asthma: Definition and limits of asthma control in the pediatric population. Front Pediatr 2018; 6: 170.
[http://dx.doi.org/10.3389/fped.2018.00170] [PMID: 29971223]
[7]
Ramratnam SK, Bacharier LB, Guilbert TW. Severe asthma in children. J Allergy Clin Immunol Pract 2017; 5(4): 889-98.
[http://dx.doi.org/10.1016/j.jaip.2017.04.031] [PMID: 28689839]
[8]
Chipps BE, Haselkorn T, Rosén K, Mink DR, Trzaskoma BL, Luskin AT. Asthma exacerbations and triggers in children in TENOR: Impact on quality of life. J Allergy Clin Immunol Pract 2018; 6(1): 169-176.e2.
[http://dx.doi.org/10.1016/j.jaip.2017.05.027] [PMID: 28803186]
[9]
Licari A, Manca E, Rispoli GA, Mannarino S, Pelizzo G, Marseglia GL. Congenital vascular rings: A clinical challenge for the pediatrician. Pediatr Pulmonol 2015; 50(5): 511-24.
[http://dx.doi.org/10.1002/ppul.23152] [PMID: 25604054]
[10]
Licari A, Castagnoli R, Denicolò CF, Rossini L, Marseglia A, Marseglia GL. The nose and the lung: United airway disease? Front Pediatr 2017; 5: 44.
[http://dx.doi.org/10.3389/fped.2017.00044] [PMID: 28316969]
[11]
Licari A, Brambilla I, De Filippo M, Poddighe D, Castagnoli R, Marseglia GL. The role of upper airway pathology as a co-morbidity in severe asthma. Expert Rev Respir Med 2017; 11(11): 855-65.
[http://dx.doi.org/10.1080/17476348.2017.1381564] [PMID: 28918658]
[12]
Licari A, Caimmi S, Bosa L, Marseglia A, Marseglia GL, Caimmi D. Rhinosinusitis and asthma: A very long engagement. Int J Immunopathol Pharmacol 2014; 27(4): 499-508.
[http://dx.doi.org/10.1177/039463201402700405] [PMID: 25572729]
[13]
Fitzpatrick AM. Severe asthma in children: lessons learned and future directions. J Allergy Clin Immunol Pract 2016; 4(1): 11-9.
[http://dx.doi.org/10.1016/j.jaip.2015.10.008] [PMID: 26772923]
[14]
Fleming L, Murray C, Bansal AT, et al. U-BIOPRED Study Group. The burden of severe asthma in childhood and adolescence: Results from the paediatric U-BIOPRED cohorts. Eur Respir J 2015; 46(5): 1322-33.
[http://dx.doi.org/10.1183/13993003.00780-2015] [PMID: 26405287]
[15]
Licari A, Castagnoli R, Brambilla I, et al. Asthma endotyping and biomarkers in childhood asthma. Pediatr Allergy Immunol Pulmonol 2018; 31(2): 44-55.
[http://dx.doi.org/10.1089/ped.2018.0886] [PMID: 30069422]
[16]
Robinson D, Humbert M, Buhl R, et al. Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy 2017; 47(2): 161-75.
[http://dx.doi.org/10.1111/cea.12880] [PMID: 28036144]
[17]
Lötvall J, Akdis CA, Bacharier LB, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011; 127(2): 355-60.
[http://dx.doi.org/10.1016/j.jaci.2010.11.037] [PMID: 21281866]
[18]
Samitas K, Zervas E, Gaga M. T2-low asthma: current approach to diagnosis and therapy. Curr Opin Pulm Med 2017; 23(1): 48-55.
[http://dx.doi.org/10.1097/MCP.0000000000000342] [PMID: 27798418]
[19]
Licari A, Castagnoli R, Brambilla I, et al. New approaches for identifying and testing potential new anti-asthma agents. Expert Opin Drug Discov 2018; 13(1): 51-63.
[http://dx.doi.org/10.1080/17460441.2018.1396315] [PMID: 29077521]
[20]
Gould HJ, Sutton BJ. IgE in allergy and asthma today. Nat Rev Immunol 2008; 8(3): 205-17.
[http://dx.doi.org/10.1038/nri2273] [PMID: 18301424]
[21]
Platts-Mills TA. The role of immunoglobulin E in allergy and asthma. Am J Respir Crit Care Med 2001; 164(8 Pt 2): S1-5.
[http://dx.doi.org/10.1164/ajrccm.164.supplement_1.2103024] [PMID: 11704610]
[22]
Durrani SR, Montville DJ, Pratt AS, et al. Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. J Allergy Clin Immunol 2012; 130(2): 489-95.
[http://dx.doi.org/10.1016/j.jaci.2012.05.023] [PMID: 22766097]
[23]
Redhu NS, Saleh A, Shan L, et al. Proinflammatory and Th2 cytokines regulate the high affinity IgE receptor (FcepsilonRI) and IgE-dependant activation of human airway smooth muscle cells. PLoS One 2009; 4(7)e6153
[http://dx.doi.org/10.1371/journal.pone.0006153] [PMID: 19582151]
[24]
Roth M, Zhong J, Zumkeller C, S’ng CT, Goulet S, Tamm M. The role of IgE-receptors in IgE-dependent airway smooth muscle cell remodelling. PLoS One 2013; 8(2)e56015
[http://dx.doi.org/10.1371/journal.pone.0056015] [PMID: 23457493]
[25]
Mitchell PD, O’Byrne PM. Epithelial-derived cytokines in asthma. Chest 2017; 151(6): 1338-44.
[http://dx.doi.org/10.1016/j.chest.2016.10.042] [PMID: 27818325]
[26]
Haselkorn T, Szefler SJ, Simons FE, et al. TENOR Study Group. Allergy, total serum immunoglobulin E, and airflow in children and adolescents in TENOR. Pediatr Allergy Immunol 2010; 21(8): 1157-65.
[http://dx.doi.org/10.1111/j.1399-3038.2010.01065.x] [PMID: 20444153]
[27]
Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med 1989; 320(5): 271-7.
[http://dx.doi.org/10.1056/NEJM198902023200502] [PMID: 2911321]
[28]
Caudri D, Wijga AH, Hoekstra MO, et al. Prediction of asthma in symptomatic preschool children using exhaled nitric oxide, Rint and specific IgE. Thorax 2010; 65(9): 801-7.
[http://dx.doi.org/10.1136/thx.2009.126912] [PMID: 20805175]
[29]
Gerald JK, Gerald LB, Vasquez MM, et al. Markers of Differential Response to Inhaled Corticosteroid Treatment Among Children with Mild Persistent Asthma. J Allergy Clin Immunol Pract 2015; 3(4): 540-6.e3.
[http://dx.doi.org/10.1016/j.jaip.2015.01.023] [PMID: 25783161]
[30]
Sears MR, Burrows B, Flannery EM, Herbison GP, Hewitt CJ, Holdaway MD. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med 1991; 325(15): 1067-71.
[http://dx.doi.org/10.1056/NEJM199110103251504] [PMID: 1891008]
[31]
Poddighe D, Brambilla I, Licari A, Marseglia GL. Omalizumab in the Therapy of Pediatric Asthma. Recent Pat Inflamm Allergy Drug Discov 2018; 12(2): 103-9.
[http://dx.doi.org/10.2174/1872213X12666180430161351] [PMID: 29714140]
[32]
Licari A, Marseglia G, Castagnoli R, Marseglia A, Ciprandi G. The discovery and development of omalizumab for the treatment of asthma. Expert Opin Drug Discov 2015; 10(9): 1033-42.
[http://dx.doi.org/10.1517/17460441.2015.1048220] [PMID: 25979110]
[33]
Holgate S, Casale T, Wenzel S, Bousquet J, Deniz Y, Reisner C. The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation. J Allergy Clin Immunol 2005; 115(3): 459-65.
[http://dx.doi.org/10.1016/j.jaci.2004.11.053] [PMID: 15753888]
[34]
MacGlashan DW Jr, Bochner BS, Adelman DC, et al. Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 1997; 158(3): 1438-45.
[PMID: 9013989]
[35]
Schroeder JT, Bieneman AP, Chichester KL, et al. Decreases in human dendritic cell-dependent T(H)2-like responses after acute in vivo IgE neutralization. J Allergy Clin Immunol 2010; 125(4): 896-901.e6.
[http://dx.doi.org/10.1016/j.jaci.2009.10.021] [PMID: 20132969]
[36]
Djukanović R, Wilson SJ, Kraft M, 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): 583-93.
[http://dx.doi.org/10.1164/rccm.200312-1651OC] [PMID: 15172898]
[37]
Riccio AM, Dal Negro RW, Micheletto C, et al. Omalizumab modulates bronchial reticular basement membrane thickness and eosinophil infiltration in severe persistent allergic asthma patients. Int J Immunopathol Pharmacol 2012; 25(2): 475-84.
[http://dx.doi.org/10.1177/039463201202500217] [PMID: 22697079]
[38]
Roth M, Zhao F, Zhong J, Lardinois D, Tamm M. Serum IgE induced airway smooth muscle cell remodeling is independent of allergens and is prevented by omalizumab. PLoS One 2015; 10(9) e0136549
[http://dx.doi.org/10.1371/journal.pone.0136549] [PMID: 26332463]
[39]
Licari A, Marseglia A, Caimmi S, et al. Omalizumab in children. Paediatr Drugs 2014; 16(6): 491-502.
[http://dx.doi.org/10.1007/s40272-014-0107-z] [PMID: 25404353]
[40]
Wang KY, Sindher SB, Stinson R, DaVeiga SP. Efficacy and safety of omalizumab in pediatric patients with high immunoglobulin E levels: A case series. Allergy Asthma Proc 2018; 39(4): 289-91.
[http://dx.doi.org/10.2500/aap.2018.39.4146] [PMID: 30095394]
[41]
Brodlie M, McKean MC, Moss S, Spencer DA. The oral corticosteroid-sparing effect of omalizumab in children with severe asthma. Arch Dis Child 2012; 97(7): 604-9.
[http://dx.doi.org/10.1136/archdischild-2011-301570] [PMID: 22685051]
[42]
Busse WW, Morgan WJ, Gergen PJ, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med 2011; 364(11): 1005-15.
[http://dx.doi.org/10.1056/NEJMoa1009705] [PMID: 21410369]
[43]
Lanier B, Bridges T, Kulus M, Taylor AF, Berhane I, Vidaurre CF. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol 2009; 124(6): 1210-6.
[http://dx.doi.org/10.1016/j.jaci.2009.09.021] [PMID: 19910033]
[44]
Teach SJ, Gill MA, Togias A, et al. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol 2015; 136(6): 1476-85.
[http://dx.doi.org/10.1016/j.jaci.2015.09.008] [PMID: 26518090]
[45]
Licari A, Castagnoli R, Panfili E, Marseglia A, Brambilla I, Marseglia GL. An update on anti-IgE therapy in pediatric respiratory diseases. Curr Respir Med Rev 2017; 13(1): 22-9.
[http://dx.doi.org/10.2174/1573398X13666170616110738] [PMID: 29290750]
[46]
Rodrigo GJ, Neffen H. Systematic review on the use of omalizumab for the treatment of asthmatic children and adolescents. Pediatr Allergy Immunol 2015; 26(6): 551-6.
[http://dx.doi.org/10.1111/pai.12405] [PMID: 25963882]
[47]
Deschildre A, Marguet C, Salleron J, et al. Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey. Eur Respir J 2013; 42(5): 1224-33.
[http://dx.doi.org/10.1183/09031936.00149812] [PMID: 23520319]
[48]
Deschildre A, Marguet C, Langlois C, et al. Real-life long-term omalizumab therapy in children with severe allergic asthma. Eur Respir J 2015; 46(3): 856-9.
[http://dx.doi.org/10.1183/09031936.00008115] [PMID: 26022964]
[49]
Licari A, Castagnoli R, Denicolò C, et al. Omalizumab in childhood asthma italian study group. omalizumab in children with severe allergic asthma: The italian real-life experience. Curr Respir Med Rev 2017; 13(1): 36-42.
[http://dx.doi.org/10.2174/1573398X13666170426094536] [PMID: 29213221]
[50]
Chipps BE, Lanier B, Milgrom H, et al. Omalizumab in children with uncontrolled allergic asthma: Review of clinical trial and real-world experience. J Allergy Clin Immunol 2017; 139(5): 1431-44.
[http://dx.doi.org/10.1016/j.jaci.2017.03.002] [PMID: 28477722]
[51]
Lommatzsch M, Korn S, Buhl R, Virchow JC. Against all odds: anti-IgE for intrinsic asthma? Thorax 2014; 69(1): 94-6.
[http://dx.doi.org/10.1136/thoraxjnl-2013-203738] [PMID: 23709757]
[52]
Licari A, Castagnoli R, Bottino C, Marseglia A, Marseglia G, Ciprandi G. Emerging drugs for the treatment of perennial allergic rhinitis. Expert Opin Emerg Drugs 2016; 21(1): 57-67.
[http://dx.doi.org/10.1517/14728214.2016.1139082] [PMID: 26733401]
[53]
Tosca MA, Licari A, Olcese R, Marseglia G, Sacco O, Ciprandi G. Immunotherapy and Asthma in Children. Front Pediatr 2018; 6: 231.
[http://dx.doi.org/10.3389/fped.2018.00231] [PMID: 30186823]
[54]
Ciprandi G, Marseglia GL, Castagnoli R, et al. From IgE to clinical trials of allergic rhinitis. Expert Rev Clin Immunol 2015; 11(12): 1321-33.
[http://dx.doi.org/10.1586/1744666X.2015.1086645] [PMID: 26358006]
[55]
Marseglia GL, Pagella F, Licari A, et al. Acute isolated sphenoid sinusitis in children. Int J Pediatr Otorhinolaryngol 2006 Dec; 70(12): 2027-31. Epub 2006 Aug 22. Review. PubMed
[PMID: 16930]
[56]
Caimmi D, Matti E, Pelizzo G, et al. Nasal polyposis in children. J Biol Regul Homeost Agents 2012; 26(1)(Suppl.): S77-83.
[PMID: 22691254]
[57]
Busse W, Haselkorn T, Rosén K, et al. Greater treatment benefit with omalizumab in children with increased asthma severity: exploratory analyses from the inner-city anti-ige therapy for asthma (ICATA) study. J Allergy Clin Immunol 2018; 141(2)(Suppl.): AB14.
[http://dx.doi.org/10.1016/j.jaci.2017.12.045]
[58]
Tajiri T, Niimi A, Matsumoto H, et al. Comprehensive efficacy of omalizumab for severe refractory asthma: A time-series observational study. Ann Allergy Asthma Immunol 2014; 113(4): 470-5.e2.
[http://dx.doi.org/10.1016/j.anai.2014.06.004] [PMID: 24994694]
[59]
Szefler SJ, Haselkorn T, Ortiz B, et al. The composite asthma severity index: A tool for assessing impact of omalizumab treatment in children with moderate-to-severe persistent allergic asthma. J Allergy Clin Immunol 2018; 141(2)(Suppl.): AB100.
[http://dx.doi.org/10.1016/j.jaci.2017.12.318]
[60]
Hanania NA, Alpan O, Hamilos DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: A randomized trial. Ann Intern Med 2011; 154(9): 573-82.
[http://dx.doi.org/10.7326/0003-4819-154-9-201105030-00002] [PMID: 21536936]
[61]
Hanania NA, Wenzel S, Rosén K, 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): 804-11.
[http://dx.doi.org/10.1164/rccm.201208-1414OC] [PMID: 23471469]
[62]
Tajiri T, Matsumoto H, Gon Y, et al. Utility of serum periostin and free IgE levels in evaluating responsiveness to omalizumab in patients with severe asthma. Allergy 2016; 71(10): 1472-9.
[http://dx.doi.org/10.1111/all.12922] [PMID: 27113353]
[63]
Milgrom H, Berger W, Nayak A, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics 2001; 108(2) E36
[http://dx.doi.org/10.1542/peds.108.2.e36] [PMID: 11483846]
[64]
Milgrom H, Fowler-Taylor A, Vidaurre CF, Jayawardene S. Safety and tolerability of omalizumab in children with allergic (IgE-mediated) asthma. Curr Med Res Opin 2011; 27(1): 163-9.
[http://dx.doi.org/10.1185/03007995.2010.539502] [PMID: 21121874]
[65]
Busse W, Buhl R, Fernandez Vidaurre C, et al. Omalizumab and the risk of malignancy: results from a pooled analysis. J Allergy Clin Immunol 2012; 129(4): 983-9.e6.
[http://dx.doi.org/10.1016/j.jaci.2012.01.033] [PMID: 22365654]
[66]
Long A, Rahmaoui A, Rothman KJ, et al. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. J Allergy Clin Immunol 2014; 134(3): 560-567.e4.
[http://dx.doi.org/10.1016/j.jaci.2014.02.007] [PMID: 24679845]
[67]
Normansell R, Walker S, Milan SJ, Walters EH, Nair P. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev 2014; 1(1) CD003559
[http://dx.doi.org/10.1002/14651858.CD003559.pub4] [PMID: 24414989]
[68]
Arm JP, Bottoli I, Skerjanec A, et al. Pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-affinity anti-IgE antibody, in atopic subjects. Clin Exp Allergy 2014; 44(11): 1371-85.
[http://dx.doi.org/10.1111/cea.12400] [PMID: 25200415]
[69]
Gauvreau GM, Arm JP, Boulet LP, et al. Efficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses. J Allergy Clin Immunol 2016; 138(4): 1051-9.
[http://dx.doi.org/10.1016/j.jaci.2016.02.027] [PMID: 27185571]
[70]
Licari A, Castagnoli R, De Sando E, Marseglia GL. Development of a peptide conjugate vaccine for inducing therapeutic anti-IgE antibodies. Expert Opin Biol Ther 2017; 17(4): 429-34.
[http://dx.doi.org/10.1080/14712598.2017.1289172] [PMID: 28132528]
[71]
Matucci A, Vultaggio A, Maggi E, Kasujee I. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respir Res 2018; 19(1): 113.
[http://dx.doi.org/10.1186/s12931-018-0813-0] [PMID: 29879991]
[72]
Bousquet J, Chanez P, Lacoste JY, et al. Eosinophilic inflammation in asthma. N Engl J Med 1990; 323(15): 1033-9.
[http://dx.doi.org/10.1056/NEJM199010113231505] [PMID: 2215562]
[73]
Garcia G, Taillé C, Laveneziana P, Bourdin A, Chanez P, Humbert M. Anti-interleukin-5 therapy in severe asthma. Eur Respir Rev 2013; 22(129): 251-7.
[http://dx.doi.org/10.1183/09059180.00004013] [PMID: 23997052]
[74]
Price DB, Rigazio A, Campbell JD, et al. Blood eosinophil count and prospective annual asthma disease burden: A UK cohort study. Lancet Respir Med 2015; 3(11): 849-58.
[http://dx.doi.org/10.1016/S2213-2600(15)00367-7] [PMID: 26493938]
[75]
NUCALA® (mepolizumab) prescribing information Available at. https://www.gsksource.com/pharma/content/dam/GlaxoSmith Kline/US/en/Prescribing_Information/Nucala/pdf/NUCALA-PI-PIL. PDF
[76]
NUCALA® (mepolizumab) EMA approval Available from. https://gskpro.com/content/dam/global/hcpportal/en_GB/products/nucala/PDF/nucala-pi.pdf
[77]
Gupta A, Bhat G, Pianosi P. What is New in the Management of Childhood Asthma? Indian J Pediatr 2018; 85(9): 773-81.
[http://dx.doi.org/10.1007/s12098-018-2705-1] [PMID: 29948729]
[78]
Flood-Page P, Swenson C, Faiferman I, et al. International Mepolizumab Study Group. 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.
[http://dx.doi.org/10.1164/rccm.200701-085OC] [PMID: 17872493]
[79]
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): 651-9.
[http://dx.doi.org/10.1016/S0140-6736(12)60988-X] [PMID: 22901886]
[80]
Ortega HG, Liu MC, Pavord ID, et al. MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014; 371(13): 1198-207.
[http://dx.doi.org/10.1056/NEJMoa1403290] [PMID: 25199059]
[81]
Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009; 360(10): 985-93.
[http://dx.doi.org/10.1056/NEJMoa0805435] [PMID: 19264687]
[82]
Bel EH, Wenzel SE, Thompson PJ, et al. SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371(13): 1189-97.
[http://dx.doi.org/10.1056/NEJMoa1403291] [PMID: 25199060]
[83]
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 2014; 133(3): 921-3.
[http://dx.doi.org/10.1016/j.jaci.2013.11.026] [PMID: 24418480]
[84]
Lugogo N, 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.e1.
[http://dx.doi.org/10.1016/j.clinthera.2016.07.010] [PMID: 27553751]
[85]
Chupp GL, Bradford ES, Albers FC, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med 2017; 5(5): 390-400.
[http://dx.doi.org/10.1016/S2213-2600(17)30125-X] [PMID: 28395936]
[86]
CINQAIR® (reslizumab) prescribing information Available at. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761033lbl.pdf
[87]
Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. Phase 3 study of reslizumab in patients with poorly controlled asthma: Effects across a broad range of eosinophil counts. Chest 2016; 150(4): 799-810.
[http://dx.doi.org/10.1016/j.chest.2016.03.018] [PMID: 27018175]
[88]
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 2015; 3(5): 355-66.
[http://dx.doi.org/10.1016/S2213-2600(15)00042-9] [PMID: 25736990]
[89]
Bjermer L, Lemiere C, Maspero J, Weiss S, Zangrilli J, Germinaro M. Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: A randomized phase 3 study. Chest 2016; 150(4): 789-98.
[http://dx.doi.org/10.1016/j.chest.2016.03.032] [PMID: 27056586]
[90]
Li J, Wang F, Lin C, et al. The efficacy and safety of reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: A systematic review and meta-analysis. J Asthma 2017; 54(3): 300-7.
[http://dx.doi.org/10.1080/02770903.2016.1212371] [PMID: 27435534]
[91]
FASENRA® (benralizumab) prescribing information Available at. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf
[92]
Bleecker ER, FitzGerald JM, Chanez P, et al. SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): A randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016; 388(10056): 2115-27.
[http://dx.doi.org/10.1016/S0140-6736(16)31324-1] [PMID: 27609408]
[93]
FitzGerald JM, Bleecker ER, Nair P, et al. CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α 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): 2128-41.
[http://dx.doi.org/10.1016/S0140-6736(16)31322-8] [PMID: 27609406]
[94]
Nair P, Wenzel S, Rabe KF, et al. ZONDA trial investigators. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med 2017; 376(25): 2448-58.
[http://dx.doi.org/10.1056/NEJMoa1703501] [PMID: 28530840]
[95]
Nowak RM, Parker JM, Silverman RA, et al. A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma. Am J Emerg Med 2015; 33(1): 14-20.
[http://dx.doi.org/10.1016/j.ajem.2014.09.036] [PMID: 25445859]
[96]
Farne HA, Wilson A, Powell C, Bax L, Milan SJ. Anti-IL5 therapies for asthma. Cochrane Database Syst Rev 2017; 9 CD010834
[PMID: 28933516]
[97]
Trivedi A, Pavord ID, Castro M. Bronchial thermoplasty and biological therapy as targeted treatments for severe uncontrolled asthma. Lancet Respir Med 2016; 4(7): 585-92.
[http://dx.doi.org/10.1016/S2213-2600(16)30018-2] [PMID: 27230825]
[98]
Nucala (mepolizumab) Product Information European Medicines Agency First published: 03/12/2015 Available at. https://www. ema.europa.eu/en/documents/product-information/nucala-epar-pro duct-information_en.pdf (Accessed on 2-Nov-2019)
[99]
Cinqair (reslizumab) Product Informtion. FDAgov Available at. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761033lbl.pdf (Accessed on 2-Nov-2019)
[100]
Pepper AN, Renz H, Casale TB, Garn H. Biologic Therapy and Novel Molecular Targets of Severe Asthma. J Allergy Clin Immunol Pract 2017; 5(4): 909-16.
[http://dx.doi.org/10.1016/j.jaip.2017.04.038] [PMID: 28689841]
[101]
Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol 2017; 13(5): 425-37.
[http://dx.doi.org/10.1080/1744666X.2017.1298443] [PMID: 28277826]
[102]
Maes T, Joos GF, Brusselle GG. Targeting interleukin-4 in asthma: lost in translation? Am J Respir Cell Mol Biol 2012; 47(3): 261-70.
[http://dx.doi.org/10.1165/rcmb.2012-0080TR] [PMID: 22538865]
[103]
Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999; 103(6): 779-88.
[http://dx.doi.org/10.1172/JCI5909] [PMID: 10079098]
[104]
Licari A, Manti S, Castagnoli R, et al. Immunomodulation in Pediatric Asthma. Front Pediatr 2019 Jul 12; 7: 289. doi: 10.3389/fped.2019.00289. eCollection 2019. Review. PubMed PMID: 31355170; PubMed Central PMCID: PMC6640202
[105]
Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med 2018; 378(26): 2486-96.
[http://dx.doi.org/10.1056/NEJMoa1804092] [PMID: 29782217]
[106]
Rabe KF, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med 2018; 378(26): 2475-85.
[http://dx.doi.org/10.1056/NEJMoa1804093] [PMID: 29782224]
[107]
Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 2013; 368(26): 2455-66.
[http://dx.doi.org/10.1056/NEJMoa1304048] [PMID: 23688323]
[108]
Bachert C, Mannent L, Naclerio RM, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: A randomized clinical trial. JAMA 2016; 315(5): 469-79.
[http://dx.doi.org/10.1001/jama.2015.19330] [PMID: 26836729]
[109]
Chang HY, Nadeau KC. IL-4Rα inhibitor for atopic disease. Cell 2017; 170(2): 222.
[http://dx.doi.org/10.1016/j.cell.2017.06.046] [PMID: 28708993]

Rights & Permissions Print Cite
Article Metrics
23
10
© 2024 Bentham Science Publishers | Privacy Policy