Subphenotypes of type 2 severe asthma in adults

Matsusaka, Masako; Fukunaga, Koichi; Kabata, Hiroki; Izuhara, Kenji; Asano, Koichiro; Betsuyaku, Tomoko

doi:10.1016/j.jaip.2017.06.015

Cited by 26 publications

(26 citation statements)

References 9 publications

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“…8e11 A cross-sectional survey conducted in northern California found that the total per-person costs for severe asthma are almost triple those for moderate asthma. 9 In Japan, although several studies 12,13 have been conducted to assess severe asthma subphenotypes in patients treated in a hospital-based setting, the clinical characteristics, disease burden, and patient behavior have not been well documented for severe asthma treated in various clinical settings, including local hospitals and clinics.…”

Section: Introductionmentioning

confidence: 99%

The Prevalence, Characteristics, and Patient Burden of Severe Asthma Determined by Using a Japan Health Care Claims Database

Sato

Ohno

Ishii

et al. 2019

Clinical Therapeutics

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Background: Recently, several new biological drugs targeting severe asthma are on the market, and various studies on severe asthma have been reported worldwide. However, in Japan, the data are still limited regarding epidemiology and burden of disease on severe asthma. This study determined the prevalence, characteristics, and burden of disease of patients with severe asthma.Methods: : This retrospective study (HO-16-16484) used a nationwide health care claims database. Severity of asthma was defined according to the treatment during the baseline period (April 1, 2014eMarch 31, 2015. Eligible patients were >15e65 years of age with asthma during the 12month baseline period and were followed up for 12 months. End points included the prevalence, characteristics, exacerbation frequency, and patient behavior in patients with severe, moderate, or mild asthma. Risk factors for exacerbations were explored in patients with all levels of asthma severity and in those with severe asthma.Findings: Among the 16,107 patients with asthma, 2.4 (95% CI, 2.1e2.6) per 100 patients had severe asthma. During the baseline period, 130 (34.0%) of 382 patients with severe asthma had 1 asthma exacerbation. The exacerbation frequency was highest in patients with severe asthma, and most of the comorbidities increased in proportion to the asthma severity. During the follow-up period, exacerbation frequency increased with asthma severity. Approximately 70% of patients with severe asthma were treated at clinics, requiring outpatient visits~10 times per year. Different exacerbation risk factors were identified between patients with all severity levels of asthma and those with severe asthma. With the severe asthma patients,

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Section: Introductionmentioning

confidence: 99%

The Prevalence, Characteristics, and Patient Burden of Severe Asthma Determined by Using a Japan Health Care Claims Database

Sato

Ohno

Ishii

et al. 2019

Clinical Therapeutics

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“…In practice, it is known that such overlap subjects are not few. In fact, from a Japanese cohort, about one-quarter of patients with severe asthma shared allergic/eosinophilic overlap [6].…”

Section: Resultsmentioning

confidence: 99%

“…In atopic/eosinophilic overlapping patients, there is no effective answer to the question: “which is the optimal choice between Anti‐IgE and anti‐Interleukin 5 (IL‐5)?” In practice, it is known that such overlap subjects are not few. In fact, from a Japanese cohort, about one‐quarter of patients with severe asthma shared allergic/eosinophilic overlap 6.…”

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confidence: 99%

Three‐step algorithm for biological therapy targeted IgE and IL‐5 in severe asthma

Oishi

Matsunaga

2018

Immunity Inflam & Disease

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IntroductionRecently, several new biological therapies targeted IgE and IL‐5 in severe asthma have been developed and approved. In the last few years, there have been some reports on the therapeutic algorithms for severe asthmatic subjects screened by biomarkers. However, these algorithms have one problem. In atopic/eosinophilic overlapping asthmatic subjects, there is no effective answer to the question: “which is the optimal choice between Anti‐IgE and anti‐IL‐5?”MethodsWe propose a new three‐step algorithm for biological therapy in severe asthma.ResultsStep 1 is to divide subjects into four groups by measuring blood eosinophils and FeNO. Step 2 is to divide the subjects further into six groups by atopy test. In the case of elevated blood eosinophils, normal/elevated FeNO, and atopy, we perform a steroid trial in step 3 in order to decide whether to select anti‐IgE or anti‐IL‐5. The steroid trial is to assess the symptoms of asthma, lung function, blood eosinophils, and FeNO before and after 14 days treatment with 0.5 mg/kg oral prednisolone/day. We judge that cases in which blood eosinophils and FeNO decrease together are not “truely steroid resistance.” In such cases, considering the possibility that allergic type inflammation through adaptive immunity is dominant, anti‐IgE is selected when it is difficult to prevent exacerbations by improving environmental factors. Conversely, we consider that cases in which blood eosinophils and/or FeNO do not decrease, are “truely steroid resistance.” In this case, since there is a possibility that non‐allergic type inflammation due to innate immunity, etc. may remain, anti‐IL‐5, which is expected to be effective for steroid‐resistant eosinophilic inflammation, is selected.ConclusionsOur three‐step algorithm including the steroid trial may be applicable to companion diagnostics testing for molecularly targeted therapies in severe asthma. Further validation is required to examine the effectiveness of this algorithm.

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“…Elevated biomarker levels, such as EOS, FeNO and IgE, are key clinical indicators of Type 2 in ammation [11,19]. EOS level is mediated by IL-4, IL-13, and IL-5 and de nes eosinophilic asthma [20,21]. FeNO level correlates with serum IgE and sputum EOS; it is mediated by IL-4 and IL-13 [22], and correlates also with allergic asthma [20,21].…”

Section: Introductionmentioning

confidence: 99%

“…EOS level is mediated by IL-4, IL-13, and IL-5 and de nes eosinophilic asthma [20,21]. FeNO level correlates with serum IgE and sputum EOS; it is mediated by IL-4 and IL-13 [22], and correlates also with allergic asthma [20,21]. Type 2 in ammation is the key driver of all Type 2 asthma phenotypes, including eosinophilic, allergic or mixed (i.e.…”

Section: Introductionmentioning

confidence: 99%

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

Canonica

Blasi

Crimi

et al. 2020

Preprint

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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.

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Subphenotypes of type 2 severe asthma in adults

Cited by 26 publications

References 9 publications

The Prevalence, Characteristics, and Patient Burden of Severe Asthma Determined by Using a Japan Health Care Claims Database

The Prevalence, Characteristics, and Patient Burden of Severe Asthma Determined by Using a Japan Health Care Claims Database

Three‐step algorithm for biological therapy targeted IgE and IL‐5 in severe asthma

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

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