Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies

Ortega, Héctor; Yancey, Steven W.; Mayer, Bhabita; Gunsoy, Necdet; Keene, Oliver N.; Bleecker, Eugene R.; Brightling, Christopher E.; Pavord, Ian D.

doi:10.1016/s2213-2600(16)30031-5

Cited by 470 publications

(381 citation statements)

References 26 publications

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“…A post hoc analysis performed in subjects treated with mepolizumab reported a greater reduction of asthma exacerbations in subjects with blood eosinophils 500 / mL compared to those with lower blood eosinophils levels. 40,44,45 Similarly, reslizumab has also been shown to lead to substantial improvements in those with eosinophils 400-500 cells/ mL; 46,47 however, trials that have included only those with blood eosinophils 400/ mL have not shown that further stratification of blood eosinophils beyond this cut off predicted greater improvements in FEV 1 , 48 or in the rate of exacerbations. 35,48 One trial assessed the effect of a single dose of benralizumab after an emergency department (ED) visit for an exacerbation and found a decreased exacerbation rate in all individuals, regardless of their baseline serum eosinophil count.…”

Section: Biomarkers Associated With Th2 Inflammationmentioning

confidence: 99%

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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Section: Biomarkers Associated With Th2 Inflammationmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…Five studies that included relevant subgroup analysis were identified, three regarding mepolizumab [30–32], and two regarding reslizumab [33,34]. In total, we included 13 studies for further analysis, and eight of those were included in the meta-analysis (see literature selection flow chart in Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma – a systematic review and meta-analysis

Henriksen

Bødtger

Sidenius³

et al. 2018

European Clinical Respiratory Journal

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Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging.Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma.Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab.Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53% (95% CI 46; 59) in favour of anti-IL-5, corresponding to –0.94 annual exacerbations (95% CI –1.08;–0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25% reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0%). One study (N = 135) contributed with data on percentage of patients experiencing ≥50% reduction inoral corticosteroid treatment, showing an effect of 20% (95% CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10%. Quality of evidence was considered low.Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome.Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures.

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“…Retrospective analyses of large phase III trials of inhaled corticosteroids in patients with moderate and severe COPD have shown that the benefit of inhaled corticosteroids added to long-acting beta agonists 21,46,47 or alone 48 on exacerbation numbers and decline in lung function are confined to patients with a blood eosinophil count > 2%. The use of the blood eosinophil count to facilitate personalized management in patients with asthma has not yet been explored extensively, but there is compelling evidence that it is a prognostic marker 26,49 and is associated with a positive response to anti-IL-5 26,50 .…”

Section: Does Personalized Management Results In Better Outcomes?mentioning

confidence: 99%

Practising Personalized Medicine in Asthma

Hynes¹,

Shrimanker²,

Pavord³

2016

BRN

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Asthma is a common and, in many cases, serious condition. After rapid improvement in outcomes following the introduction of the first guidelines in 1990, progress in this area has stalled. Current treatments follow a "one size fits all" approach without acknowledgement of the many different underlying disease mechanisms that drive the morbidity of asthma. Personalized medicine allows us to instead direct treatments at these specific causal mechanisms, targeting the exact pathology present in each patient. We believe that with this approach not only will we improve patient outcomes, we will also open the door to novel areas of research and drug discovery. In this article we describe where we are presently with the move towards personalized medicine in asthma, firstly explaining why we believe our current approach is insufficient, and secondly outlining in practical terms how physicians can adopt this novel approach when treating patients with asthma in clinics today. (BRN Rev. 2016;2:229-38) Corresponding author: Ian Pavord, Ian.pavord@ndm.ox.ac.uk

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Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies

Cited by 470 publications

References 26 publications

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

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

Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma – a systematic review and meta-analysis

Practising Personalized Medicine in Asthma

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