Real-life evaluation of mepolizumab efficacy in patients with severe eosinophilic asthma, according to atopic trait and allergic phenotype.
IL-5
allergen sensitization
atopy
exacerbations
mepolizumab
severe eosinophilic asthma
Journal
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN: 1365-2222
Titre abrégé: Clin Exp Allergy
Pays: England
ID NLM: 8906443
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
12
02
2020
revised:
29
03
2020
accepted:
21
04
2020
pubmed:
30
4
2020
medline:
13
8
2021
entrez:
30
4
2020
Statut:
ppublish
Résumé
Anti-interleukin-5 (IL-5) monoclonal antibodies can be used as add-on biological therapies in allergic and non-allergic patients with severe eosinophilic asthma. However, within such a therapeutic context real-life investigations are lacking. Therefore, the aim of the present observational study was to evaluate the effects of mepolizumab in allergic and non-allergic subjects with severe eosinophilic asthma. Relevant clinical, functional, laboratory, and pharmacotherapeutic parameters were assessed in the above patient subgroups. After one year of add-on biological treatment with mepolizumab, our 88 patients experienced a remarkable improvement of their severe asthma, documented by a better symptom control, expressed by a significant improvement in asthma control test (ACT) score. Indeed, the mean value (±standard deviation) of ACT score increased from 12.55 (±3.724) to 21.08 (±3.358). Moreover, significant improvements were also detected with regard to the median values (interquartile range) of forced expiratory volume in one second (FEV Hence, our real-life data suggest that mepolizumab can represent a valid add-on therapeutic option for patients with severe eosinophilic asthma, irrespective of IgE serum concentrations, and allergic sensitization.
Sections du résumé
BACKGROUND
Anti-interleukin-5 (IL-5) monoclonal antibodies can be used as add-on biological therapies in allergic and non-allergic patients with severe eosinophilic asthma. However, within such a therapeutic context real-life investigations are lacking.
OBJECTIVE
Therefore, the aim of the present observational study was to evaluate the effects of mepolizumab in allergic and non-allergic subjects with severe eosinophilic asthma.
METHODS
Relevant clinical, functional, laboratory, and pharmacotherapeutic parameters were assessed in the above patient subgroups.
RESULTS
After one year of add-on biological treatment with mepolizumab, our 88 patients experienced a remarkable improvement of their severe asthma, documented by a better symptom control, expressed by a significant improvement in asthma control test (ACT) score. Indeed, the mean value (±standard deviation) of ACT score increased from 12.55 (±3.724) to 21.08 (±3.358). Moreover, significant improvements were also detected with regard to the median values (interquartile range) of forced expiratory volume in one second (FEV
CONCLUSION AND CLINICAL RELEVANCE
Hence, our real-life data suggest that mepolizumab can represent a valid add-on therapeutic option for patients with severe eosinophilic asthma, irrespective of IgE serum concentrations, and allergic sensitization.
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Immunoglobulin E
37341-29-0
mepolizumab
90Z2UF0E52
Prednisone
VB0R961HZT
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
780-788Informations de copyright
© 2020 John Wiley & Sons Ltd.
Références
To T, Stanojevic S, Moores G, et al. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health. 2012;12:204.
Pelaia G, Vatrella A, Busceti MT, et al. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma. Mediators Inflamm. 2015;2015:879783.
Khalaf K, Paoletti G, Puggioni F, et al. Asthma from immune pathogenesis to precision medicine. Semin Immunol. 2019;46:101294.
Holgate ST, Wenzel S, Postma DS, Weiss ST, Renz H, Sly PD. Asthma. Nat Rev Dis Primers. 2015;1:15025.
Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet. 2018;391:783-800.
Bousquet J, Chanez P, Lacoste JY, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990;323:1033-1039.
Heffler E, Blasi F, Latorre M, et al. SANI network. The severe asthma network in Italy: findings and perspectives. J Allergy Clin Immunol Pract. 2019;7:1462-1468.
Schleich F, Brusselle G, Louis R, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian severe asthma registry (BSAR). Respir Med. 2014;108:1723-1732.
Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56:219-233.
Lambrecht BN, Hammad H, Fahy JV. The cytokines of asthma. Immunity. 2019;50:975-991.
Tran TN, Zeiger RS, Peters SP, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116:37-42.
Zhang X, Moilanen CE, Kankaanranta H. Enhancement of human eosinophil apoptosis by fluticasone propionate, budesonide, and beclomethasone. Eur J Pharmacol. 2000;406:325-332.
Pelaia C, Vatrella A, Lombardo N, et al. Biological mechanisms underlying the clinical effects of allergen-specific immunotherapy in asthmatic children. Expert Opin Biol Ther. 2018;18:197-204.
Dunican EM, Fahy JV. Asthma and corticosteroids: time for a more precise approach to treatment. Eur Respir J. 2017;49:1701167.
Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013;131:636-645.
Pelaia C, Vatrella A, Crimi C, Gallelli L, Terracciano R, Pelaia G. Clinical relevance of understanding mitogen-activated protein kinases involved in asthma. Expert Rev Respir Med. 2020;14(5):501-510.
Siddiqui S, Denlinger LC, Fowler SJ, et al. Unmet needs in severe asthma subtyping and precision medicine trials. Bridging clinical and patient perspectives. Am J Respir Crit Care Med. 2019;199:823-829.
Global Initiative for Asthma, 2019 update. www.ginasthma.org
Pelaia C, Calabrese C, Terracciano R, de Blasio F, Vatrella A, Pelaia G. Omalizumab, the first available antibody for biological treatment of asthma: more than a decade of real life effectiveness. Ther Adv Respir Dis. 2018;12:1753466618810192.
Pelaia C, Calabrese C, Barbuto S, et al. Omalizumab lowers asthma exacerbations, oral corticosteroid intake and blood eosinophils: results of a 5-year single-centre observational study. Pulm Pharmacol Ther. 2019;54:25-30.
Pelaia C, Vatrella A, Busceti MT, et al. Severe eosinophilic asthma: from the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab. Drug Des Devel Ther. 2017;11:3137-3144.
Pelaia C, Busceti MT, Solinas S, Terracciano R, Pelaia G. Real-life evaluation of the clinical, functional, and hematological effects of mepolizumab in patients with severe eosinophilic asthma: results of a single-centre observational study. Pulm Pharmacol Ther. 2018;53:1-5.
Sposato B, Camiciottoli G, Bacci E, et al. Mepolizumab effectiveness on small airway obstruction, corticosteroid sparing and maintenance therapy step-down in real life. Pulm Pharmacol Ther. 2020;61:101899.
Pelaia G, Vatrella A, Busceti MT, et al. Role of biologics in severe eosinophilic asthma - focus on reslizumab. Ther Clin Risk Manag. 2016;12:1075-1082.
Pelaia C, Vatrella A, Bruni A, Terracciano R, Pelaia G. Benralizumab in the treatment of severe asthma: design, development and potential place in therapy. Drug Des Devel Ther. 2018;21:619-628.
Pelaia C, Calabrese C, Vatrella A, et al. Benralizumab: from the basic mechanism of action to the potential use in the biological therapy of severe eosinophilic asthma. Biomed Res Int. 2018;2018:1-9.
Pelaia C, Vatrella A, Gallelli L, et al. Dupilumab for the treatment of asthma. Expert Opin Biol Ther. 2017;17:1565-1572.
Albers FC, Mullerova H, Gunsoy NB, et al. Biologic treatment eligibility for real-world patients with severe asthma: the IDEAL study. J Asthma. 2018;55:152-160.
Humbert M, Albers FC, Bratton DJ, et al. Effect of mepolizumab in severe eosinophilic asthma according to omalizumab eligibility. Respir Med. 2019;154:69-75.
Chipps BE, Newbold P, Hirsch I, Trudo F, Goldman M. Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2018;120:504-511.
Corren J, Castro M, O’Riordan T, et al. Dupilumab efficacy in patients with uncontrolled, moderate-to-severe allergic asthma. J Allergy Clin Immunol Pract. 2020;8:516-526.
Pelaia C, Busceti MT, Vatrella A, et al. Real-life rapidity of benralizumab effects in patients with severe allergic eosinophilic asthma: assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after the first drug dose. Pulm Pharmacol Ther. 2019;58:101830.
Hentges F, Leonard C, Arumugam K, Hilger C. Immune responses to inhalant mammalian allergens. Front Immunol. 2014;5:234.
Froidure A, Mouthuy J, Durham SR, Chanez P, Sibille Y, Pilette C. Asthma phenotypes and IgE responses. Eur Respir J. 2016;47:304-319.
Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343-373.
Graham BL, Steenbruggen I, Miller MR, et al. Standardization of spirometry 2019 update. An official American Thoracic Society and European Respiratory Society technical statement. Am J Respir Crit Care Med. 2019;200:e70-e88.
Bagnasco D, Milanese M, Rolla G, et al. The North-Western Italian experience with anti IL-5 therapy and comparison with regulatory trials. World Allergy Organ J. 2018;11:34.
Bagnasco D, Caminati M, Menzella F, et al. One year of mepolizumab. Efficacy and safety in real-life in Italy. Pulm Pharmacol Ther. 2019;58:101836.
Pertzov B, Unterman A, Shtraichman O, Shitenberg D, Rosengarten D, Kramer MR. Efficacy and safety of mepolizumab in a real-world cohort of patients with severe eosinophilic asthma. J Asthma. 2020. https://doi.org/10.1080/02770903.2019.1658208. [Epub ahead of print].
Kurosawa M, Sutoh E. Prospective open-label study of 48-week subcutaneous administration of mepolizumab in Japanese patients with severe eosinophilic asthma. J Investig Allergol Clin Immunol. 2019;29:40-45.
Schleich F, Graff S, Nekoee H, et al. Real-world experience with mepolizumab: does it deliver what it has promised? Clin Exp Allergy. 2020. https://doi.org/10.1111/cea.13601. [Epub ahead of print].
Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189-1197.
Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371:1198-1207.
Jia CE, Zhang HP, Lv Y, et al. The asthma control test and the asthma control questionnaire for assessing asthma control: systematic review and meta-analysis. J Allergy Clin Immunol. 2013;131:695-703.
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 randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase 3b trial. Lancet Respir Med. 2017;5:390-400.
Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380:651-659.
Yancey SW, Keene ON, Albers FC, et al. Biomarkers for severe eosinophilic asthma. J Allergy Clin Immunol. 2017;140:1509-1518.
Drick N, Seeliger B, Welte T, Fuge J, Suhling H. Anti-IL-5 therapy in patients with severe eosinophilic asthma - clinical efficacy and possible criteria for treatment response. BMC Pulm Med. 2018;18:119.
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;3:849-858.
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. 2014;2:741-750.
Gunsoy NB, Cockle SM, Yancey SW, et al. Evaluation of potential continuation rules for mepolizumab treatment of severe eosinophilic asthma. J Allergy Clin Immunol Pract. 2018;6:874-882.
Bai TR, Vonk JM, Postma DS, Boezen HM. Severe exacerbations predict excess lung function decline in asthma. Eur Respir J. 2007;30:452-456.
Canonica GW, Colombo GL, Bruno GM, et al. Shadow cost of oral corticosteroids-related adverse events: a pharmacoeconomic evaluation applied to real-life data from the Severe Asthma Network in Italy (SANI) registry. World Allergy Organ J. 2019;12:100007.
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;38:2058-2070.
Pelaia C, Paoletti G, Puggioni F, et al. Interleukin-5 in the pathophysiology of severe asthma. Front Physiol. 2019;10:1514.
Dorman SC, Efthimiadis A, Babirad I, et al. Sputum CD34+ IL-5Rα+ cells increase after allergen: evidence for in situ eosinophilopoiesis. Am J Respir Crit Care Med. 2004;169:573-577.
Valent P, Dahinden CA. Role of interleukins in the regulation of basophil development and secretion. Curr Opin Hematol. 2010;17:60-66.
Kaiko G, Horvat JC, Beagley KW, Hansbro PM. Immunological decision-making: how does the immune system decide to mount a helper T-cell response? Immunology. 2008;123:326-338.
Yanagibashi T, Satoh M, Nagai Y, Koike M, Takatsu K. Allergic diseases: from bench to clinic - contribution of the discovery of interleukin-5. Cytokine. 2017;98:59-70.
Bland JM, Altman DG. Some examples of regression towards the mean. BMJ. 1994;309:780.
Levine M, Ensom MH. Post-hoc power analysis: an idea whose time has passed? Pharmacotherapy. 2001;21:405-409.