Mepolizumab versus placebo for asthma

Powell, Colin; Milan, Stephen J; Dwan, Kerry; Bax, Lynne; Walters, Nicola

doi:10.1002/14651858.cd010834.pub2

Cited by 51 publications

(36 citation statements)

References 124 publications

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“…115 A Cochrane review was published in 2015. 116 The literature search was performed in 2013 and updated in 2014. Eight studies on 1,707 individuals were selected.…”

Section: Mepolizumabmentioning

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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“…115 A Cochrane review was published in 2015. 116 The literature search was performed in 2013 and updated in 2014. Eight studies on 1,707 individuals were selected.…”

Section: Mepolizumabmentioning

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

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“…Most of these results were expected [26,27], but a global meta-analysis was lacking. Here, we selected significant studies and aggregated the results.…”

Section: Probability Of the Best Increase In Fevmentioning

confidence: 99%

Comparison of anti‐interleukin‐5 therapies in patients with severe asthma: global and indirect meta‐analyses of randomized placebo‐controlled trials

Cabon

Molinari

Marin

et al. 2016

Clin Experimental Allergy

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SummaryInconsistent results have been reported regarding IL-5 blockade treatment in asthma. There were no direct between-treatment comparisons. Only differences between each drug and placebo were studied. We identified all RCTs with anti-IL5 treatments for patients with asthma over the 1990-September 2015 period. RCTs were searched on Medline, Cochrane and Embase. At least 50 patients were enrolled in each study. Outcomes considered were exacerbation rate reduction, FEV 1 changes, ACQ-5 improvement, adverse events and serious adverse events. A global meta-analysis was first conducted followed by an indirect comparison of each IL-5-targeting drug: benralizumab, reslizumab and mepolizumab. Further eosinophilic subgroup analysis and sensitivity analysis were also conducted in case of heterogeneity. Ten trials involving 3421 patients were eligible for meta-analysis. IL-5 blockade significantly reduced annual exacerbation rates vs. placebo by 40% [29-50] (P < 0.01, I 2 = 0.61). ACQ-5 was significantly improved vs. placebo but below the recognized MCID level (À0.31 [À0.41, À0.21], P < 0.01, I 2 = 0.11). FEV 1 changes from baseline were improved vs. placebo by 0.09 L [0.05-0.12] (P < 0.01, I 2 = 0.28). The subgroup analysis identified a slight additional improvement in mean treatment effects in eosinophilic (> 300 mm 3 /L) patients with severe asthma. Similar patterns and rates of adverse events and severe adverse events were reported with the three drugs. The data interpretations were not affected by the sensitivity analysis. IL-5 blockade appears to be a relevant treatment strategy to improve severe asthma management, particularly for eosinophilic patients. No clear superiority appeared between the drugs when appropriate doses were compared.

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“…However, since varied baseline of patients among studies, it is not possible to draw a firm conclusion. Different from previous systematic reviews that only included studies of on mepolizumab [38, 39], we included trials about mepolizumab and other two anti-interleukin-5 antibodies-reslizumab and benralizumab. Additionally, the results should be interpreted with caution due to with the relatively small sample sizes and small number of included trials.…”

Section: Discussionmentioning

confidence: 99%

“…Only three or four studies reported detailed data, therefore we could not draw exact conclusions for these two parameters due to the insufficient data. Previous two systematic reviews failed to show a significant effect in FEV 1 , likely due to small number of trials analyzed [38, 39]. Liu et al [39] converted and pooled continuous variable data such as blood and sputum eosinophils.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Anti-Interleukin-5 Therapy in Patients with Asthma: A Systematic Review and Meta-Analysis

et al. 2016

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BackgroundRecent trials have assessed the efficacy and safety of novel monoclonal antibodies such as reslizumab and benralizumab. However, the overall efficacy and safety anti—interleukin (IL) 5 treatment in asthma have not been thoroughly assessed.MethodsRandomized controlled trials (RCTs) of anti-IL-5 treatment on patients with asthma published up to October 2016 in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) that reported pulmonary function, quality of life scores, asthmatic exacerbation rate, blood and sputum eosinophil counts, short-acting β-agonist (SABA) rescue use, and adverse events were included. The pooled mean difference, and relative risks (RR), and 95% confidence intervals (CIs) were calculated using random-effects models.ResultsTwenty studies involving 7100 patients were identified. Pooled analysis revealed significant improvements in FEV1 (first second forced expiratory volume) (MD = 0.09, 95% CI: 0.06–0.12, I2 = 10%), FEV1% (MD = 3.75, 95% CI: 1.66–5.83, I2 = 19%), Asthma Quality of Life Questionnaire (AQLQ) score (MD = 0.22, 95% CI: 0.15–0.30, I2 = 0%), decreased blood, sputum eosinophils and asthmatic exacerbation (RR = 0.66, 95% CI: 0.59–0.73, I2 = 51%); peak expiratory flow (PEF) (MD = 5.45, 95% CI: -2.83–13.72, I2 = 0%), histamine PC20 (MD = -0.62, 95% CI: -1.92–0.68, I2 = 0%) or SABA rescue use (MD = -0.11, 95% CI: -0.3–0.07, I2 = 30%) were unaffected; adverse events were not increased (RR = 0.93, 95% CI: 0.89–0.98, I2 = 46%). No publication bias was observed (Egger's P = 0.78).ConclusionsAnti-interleukin 5 monoclonal therapies for asthma could be safe for slightly improving FEV1 (or FEV1% of predicted value), quality of life, and reducing exacerbations risk and blood and sputum eosinophils, but have no significant effect on PEF, histamine PC20, and SABA rescue use. Further trials required to establish to clarify the optimal antibody for different patients.

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Mepolizumab versus placebo for asthma

Cited by 51 publications

References 124 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

Comparison of anti‐interleukin‐5 therapies in patients with severe asthma: global and indirect meta‐analyses of randomized placebo‐controlled trials

Efficacy and Safety of Anti-Interleukin-5 Therapy in Patients with Asthma: A Systematic Review and Meta-Analysis

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