Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma

Nair, Parameswaran; Wenzel, Sally E.; Rabe, Klaus F.; Bourdin, Arnaud; Lugogo, Njira L; Kuna, Piotr; Barker, Peter; Sproule, Stephanie; Ponnarambil, Sandhia; Goldman, Mitchell

doi:10.1056/nejmoa1703501

Cited by 856 publications

(829 citation statements)

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“…With benralizumab treatment, these patients had consistent improvements in exacerbation reduction, in lung function based on FEV 1 , and in disease-specific, health-related quality of life based on AQLQ score. Recently, the ZONDA study demonstrated that benralizumab treatment substantially reduced oral glucocorticoid use for patients with blood eosinophil counts !150 cells/lL, further supporting potential use of this agent in this patient population 25 . Numerical differences in these measures were observed for the subset of patients with blood eosinophil counts <150 cells/lL.…”

Section: Discussionmentioning

confidence: 75%

The association between blood eosinophil count and benralizumab efficacy for patients with severe, uncontrolled asthma: subanalyses of the Phase III SIROCCO and CALIMA studies

Goldman

Hirsch

Zangrilli

et al. 2017

Current Medical Research and Opinion

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Section: Discussionmentioning

confidence: 75%

The association between blood eosinophil count and benralizumab efficacy for patients with severe, uncontrolled asthma: subanalyses of the Phase III SIROCCO and CALIMA studies

Goldman

Hirsch

Zangrilli

et al. 2017

Current Medical Research and Opinion

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Section: Reslizumabmentioning

confidence: 99%

“…52,53,118 Benralizumab has also been associated with a significant reduction in oral prednisone dose. 118 In phase 3 clinical trials, benralizumab also improved pre-bronchodilator FEV 1 by approximately 100-160 mL compared to placebo, asthma-specific QoL symptom score as measured by the AQLQ by 0.08 -0.23, and asthma control as measured by the ACQ-6. 52,53 After three induction doses at four weekly intervals the administration of benralizumab every 8 weeks seems to be more effective than every 4 weeks, which may have theoretical advantages for patient care compared to medications requiring more frequent administration.…”

Section: Reslizumabmentioning

confidence: 99%

“…52,53,118 Serious adverse events deemed to be related to the study treatment, included: worsening asthma, allergic granulomatous angiitis, panic attack, paresthesia, pneumonia, heart failure, urticaria, and herpes zoster. Two serious adverse events deemed to be related to the study treatment in the placebo group: non-cardiac chest pain, injection-site erythema.…”

Section: Reslizumabmentioning

confidence: 99%

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Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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RATIONALE: While severe asthma affects approximately 5% of all individuals with asthma, this small minority of individuals accounts for a large proportion of the asthma-related costs. Greater understanding of the pathophysiology of asthma combined with the emergence of novel biologic therapies for severe asthma supported the need for a thorough review of the diagnosis, investigation, phenotyping, and management of severe asthma. OBJECTIVES: We aimed to propose a practical approach to distinguish uncontrolled asthma due to inadequate asthma management from severe asthma despite optimal asthma management. Moreover, based on emerging scientific evidence, we sought to provide guidance for characterizing individuals with severe asthma and considering a phenotype-specific management. We also aimed to review other novel new potential therapeutic approaches. METHODS: We systematically reviewed the relevant literature focusing on randomized controlled trials and when available, systematic reviews of randomized controlled trials. The proposed key messages, based on scientific evidence and expert opinion, were agreed upon by unanimous consensus. MAIN RESULTS: We defined severe asthma and outlined its significant impact from the societal and patient perspectives. We outlined a practical approach to distinguish severe from uncontrolled but not severe asthma, based on stepwise investigation and management of potential reasons for uncontrolled asthma. After reviewing the current evidence we concluded that: 1) Several biomarkers (e.g. sputum or blood eosinophil count, total IgE, or FeNO) can help identify potential responders to new therapeutic options; 2) Tiotropium may be considered as an add-on therapy for individuals 12 years of age and over with severe asthma uncontrolled despite combination ICS/LABA therapy; 3) The chronic use of macrolides may decrease asthma exacerbations in individuals 18 years of age and over with severe asthma independent of their inflammatory profile; 4) Children aged 6 years and older and adults who are sensitized to at least one relevant perennial allergen and who remain poorly controlled asthmatics despite high dose ICS and a second controller can benefit from the addition of anti-IgE therapy to reduce asthma exacerbations; due to the known risk of side effects associated with high-dose ICS in children, omalizumab should also be considered in children and adolescents who repeatedly exacerbate or have poor control when therapy is stepped down from high-dose to moderate-dose ICS and at least one other controller; 5) Anti-IL5 therapies may be considered for adults 18 years of age and over with severe eosinophilic asthma who experience recurrent asthma exacerbations in spite of high doses of ICS in addition to at least one other controller; and 6) Although bronchial thermoplasty has shown a decrease in asthma exacerbations in one study, its role in the treatment of severe asthma remains uncertain. CONCLUSIONS: After reviewing existing and emerging therapies for severe asthma, we developed ke...

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“…Many trials have verified a statistically significant and clinically meaningful reduction in daily maintenance OCS use compared with placebo for patients with severe, uncontrolled OCS‐dependent asthma receiving molecularly targeted treatment 1, 2. Although molecularly targeted treatment shows dramatic efficacy that cannot be experienced with ICS, it does not necessarily show effectiveness in all cases.…”

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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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Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma

Abstract: Benralizumab showed significant, clinically relevant benefits, as compared with placebo, on oral glucocorticoid use and exacerbation rates. These effects occurred without a sustained effect on the FEV. (Funded by AstraZeneca; ZONDA ClinicalTrials.gov number, NCT02075255 .).

Cited by 856 publications

References 18 publications

The association between blood eosinophil count and benralizumab efficacy for patients with severe, uncontrolled asthma: subanalyses of the Phase III SIROCCO and CALIMA studies

The association between blood eosinophil count and benralizumab efficacy for patients with severe, uncontrolled asthma: subanalyses of the Phase III SIROCCO and CALIMA studies

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

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

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