Defining type 2 asthma and patients eligible for dupilumab in Italy: a biomarker-based analysis

被引：3

作者：

Canonica G.W. ^{[1
,2
]}

Blasi F. ^{[3
]}

Crimi N. ^{[4
,5
]}

Paggiaro P. ^{[6
]}

Papi A. ^{[7
]}

Fanelli F. ^{[8
]}

Stassaldi A. ^{[8
]}

Furneri G. ^{[9
]}

机构：

[1] Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Via Manzoni 56, Rozzano, 20089, MI

[2] Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI

[3] Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center and Department of Pathophysiology and Transplantation, University of Milan, Milan

[4] Respiratory Medicine Unit, A.O.U. Policlinico-Vittorio Emanuele, Catania

[5] Department of Clinical and Experimental Medicine, University of Catania, Catania

[6] Department of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Pisa

[7] Respiratory Medicine Unit, Department of Medical Sciences, University of Ferrara, Ferrara

[8] Sanofi S.P.A., Milan

[9] EBMA Consulting S.R.L., Via per Carpiano 2, Melegnano, 20077, MI

来源：

Clinical and Molecular Allergy | / 19卷 / 1期

关键词：

Biomarkers; Dupilumab; Italy; Type; 2; asthma;

D O I：

10.1186/s12948-021-00146-9

中图分类号：

学科分类号：

摘要：

Background: Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status. Methods: A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: (1) estimating the total number of asthma patients in Italy (using 2016–2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); (2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); (3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); (4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab). Results: According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population). Conclusions: There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions. © 2021, The Author(s).

引用

共 44 条

[1]

Holgate S.T., Wenzel S., Postma D.S., Weiss S.T., Renz H., Sly P.D., Asthma, Nat Rev Dis Prim, 1, (2015)

[2]

Masoli M., Fabian D., Holt S., Beasley R., The global burden of asthma executive summary of the GINA dissemination committee report, Allergy, (2004)

[3]

Chanez P., Humbert M., Asthma: still a promising future?, Eur Respir Rev, (2014)

[4]

Global Asthma Network. the Global Asthma Report, (2018)

[5]

Dharmage S.C., Perret J.L., Custovic A., Epidemiology of asthma in children and adults, Front Pediatr, 7, pp. 1-15, (2019)

[6]

Kuruvilla M.E., Lee F.E.H., Lee G.B., Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease, Clin Rev Allergy Immunol, 56, pp. 219-233, (2019)

[7]

Fahy J.V., Type 2 inflammation in asthma-present in most, absent in many, Nat Rev Immunol, (2015)

[8]

Santini G., Mores N., Malerba M., Mondino C., Anzivino R., Macis G., Et al., Dupilumab for the treatment of asthma, Expert Opin Investig Drugs, 26, pp. 357-366, (2017)

[9]

Seys S.F., Scheers H., Van den Brande P., Marijsse G., Dilissen E., Van Den Bergh A., Et al., Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients, Respir Res, 18, (2017)

[10]

Peters M.C., Mekonnen Z.K., Yuan S., Bhakta N.R., Woodruff P.G., Fahy J.V., Measures of gene expression in sputum cells can identify T H2-high and TH2-low subtypes of asthma, J Allergy Clin Immunol, 133, pp. 388-394, (2014)

← 1 2 3 4 5 →