Mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/body mass index: meta-analysis of MENSA and MUSCA

Albers, Frank C.; Papi, Alberto; Taillé, Camille; Bratton, Daniel J.; Bradford, Eric; Yancey, Steven W.; Kwon, Namhee

doi:10.1186/s12931-019-1134-7

Cited by 39 publications

(36 citation statements)

References 24 publications

(39 reference statements)

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“…Other studies evaluated some socio-demographic factors (ie, allergy, BMI, eosinophils, and lung function at baseline, age, sex, and smoking habits) and 2 of them identified potential predictive factors of MEPO response. 25 , 30 , 31 A supervised cluster analysis with a recursive partitioning approach applied to the Dose Ranging Efficacy And safety with Mepolizumab (DREAM) data identified BMI as a predictor. 30 However, the data on this topic are rather controversial, and there is no general agreement as to the role of BMI as a predictive factor of outcome.…”

Section: Discussionmentioning

confidence: 99%

Real-life effectiveness of mepolizumab in patients with severe refractory eosinophilic asthma and multiple comorbidities

Crimi

Campisi

Cacopardo

et al. 2020

World Allergy Organization Journal

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Background Data on mepolizumab in patients with severe eosinophilic asthma (EA) and comorbidities are needed to assess whether randomized controlled trial results are applicable in the real world. Objective To evaluate real-life effectiveness and the presence/absence of predictors of treatment response in patients with one or more comorbidities (nasal polyps, allergic rhinitis, gastro-esophageal reflux disease, nonallergic rhinitis with eosinophilia syndrome, obesity, bronchiectasis) who received mepolizumab (MEPO) for the treatment of severe EA. Methods We performed a single-center retrospective study in patients with severe asthma and presence of comorbidities treated with mepolizumab at the respiratory outpatient clinic, Policlinico-Vittorio Emanuele, Catania, Italy. Health records of 31 severe asthmatic patients were retrieved and analyzed. Asthma control test (ACT) score, blood eosinophil count, forced expiratory volume in 1 s (FEV 1 ), FEV 1 % of predicted and FEV 1 /FVC (Forced Vital Capacity) ratio, oral corticosteroid (OCS) dosage, and exacerbations were recorded at baseline (T0), after 3 (T1), 6 (T3), 9 (T6), and 12 months (T12). Clinical response was defined when 3 of these 4 criteria were fulfilled: i) 30% exacerbation decrease; ii) 80% blood eosinophilia reduction; iii) 3 point ACT increase; iv) FEV 1 increase ≥200 mL. Results 83.87% of patients were classified as responsive to MEPO treatment. Substantial depletion of the blood eosinophils (>80%) was found in 87.1% of patients, FEV 1 > 200 mL was seen in 54.84% of patients, a 3-point ACT improvement from baseline was recorded in 80.65% 25 of patients and a 30% reduction of exacerbations rates was seen in 96.77% of patients. Moreover, the majority 38.71% of patients met 3/4 parameters after 12 months. Neither the comorbidities nor other characteristics (sex, BMI, age, smoking) influenced treatment response. Conclusions MEPO in patients with severe EA is effective regardless of the presence of comorbidities.

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Section: Discussionmentioning

confidence: 99%

Real-life effectiveness of mepolizumab in patients with severe refractory eosinophilic asthma and multiple comorbidities

Crimi

Campisi

Cacopardo

et al. 2020

World Allergy Organization Journal

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“…Other studies evaluated some socio-demographic factors (e.g. allergy, BMI, eosinophils and lung function at baseline, age, sex and smoking habits) and two of them identified potential predictive factors of MEPO response [25,30,31]. A supervised cluster analysis with a recursive partitioning approach applied to the Dose Ranging Efficacy And safety with Mepolizumab (DREAM) data identified BMI as a predictor.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of mepolizumab in a real-life cohort of patients with severe refractory eosinophilic asthma and multiple comorbidities

Crimi

Campisi

Cacopardo

et al. 2020

Preprint

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Background: Patients with severe asthma often suffer from comorbidities whose impact on the course of biological therapy has not been elucidated yet. Objective: This study evaluated, for the first time, patients with one or more comorbidities who received mepolizumab (MEPO) for the treatment of severe eosinophilic asthma to assess its real-life effectiveness and to explore the presence/absence of predictors of treatment response. Methods: Health records of 31 patients prescribed with MEPO were retrospectively analysed. Asthma control test (ACT) score, blood eosinophil count, forced expiratory volume in 1 second (FEV1), FEV1% of predicted and FEV1/FVC (Forced Vital Capacity) ratio, oral corticosteroid (OCS) dosage and exacerbations were recorded at baseline (T0), after 3 (T1), 6 (T3), nine (T6) and 12 months (T12). A clinical response was defined as: i) 30% exacerbation decrease; ii) 80% blood eosinophilia reduction; iii) 3 point ACT increase; iv) FEV1 increase ≥ 200 mL. Results: At T12 blood eosinophil level decreased by 89.89% (p>0.0001), a minimally clinical important difference in ACT score (an improvement in ACT of 3 points from baseline) was recorded in 80.65% of patients (p>0.0001) and 96.77% of patients reduced by minimum 30% the number of exacerbations (p>0.0001). 84% of patients discontinued OCS (p>0.0001). FEV1 increased by 9% (p=0.0224) while FEV1/FVC was statistically significant only at T1. No significant differences were generally found among patients with a specific comorbidity. Patients without nasal polyps showed a greater blood eosinophilia reduction than patients with nasal polyps (p=0.0395), and patients with allergy, showed a greater ACT improvement than those without (p=0.048). The number of comorbidities did not influenced treatment with MEPO. Neither the comorbidities nor other characteristics of patients at baseline (sex, BMI, age, smoking, baseline eosinophil level) influenced MEPO therapy. Conclusions: These data indicate that MEPO effectiveness in patients with severe eosinophilic asthma, regardless the presence of one or more comorbidities.

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“…77 A recent meta-analysis has shown, however, that a fixed dose of mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/ BMI. 78 Contrary to fixed doses, the anti-IL-5 antibody reslizumab is dosed according to body weight. Thus, patients with obesity may require higher doses.…”

Section: Current Therapeutic Interventions: Where Do We Stand?mentioning

confidence: 99%

<p>Metabolic Dysfunction and Asthma: Current Perspectives</p>

Pité¹,

Aguiar²,

Morello³

et al. 2020

JAA

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The increasing knowledge of the mechanisms involved in metabolism is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Metabolic dysfunction is recognized in obesity-associated asthma, but other metabolic conditions have been shown to be independently related to asthma. Novel insights have also recently been brought by metabolomics in this filed. The purpose of this review is to discuss current perspectives regarding metabolic dysfunction in asthma, from obesity-related asthma to other metabolic conditions and the role of current pharmacological therapeutic strategies and lifestyle interventions. Obesity is a well-recognized risk factor for asthma across the lifespan, which is generally associated with poorer response to current available treatments, rendering a more severe, refractory disease status. Besides the epidemiological and clinical link, untargeted metabolomics studies have recently supported the obesity-associated asthma phenotype at the molecular level. Not only obesity-related, but also other aspects of metabolic dysregulation can be independently linked to asthma. These include hyperinsulinemia, dyslipidemia and hypertension, which need to be taken into account, even in the non-obese patient. Untargeted metabolomics studies have further highlighted several other metabolic pathways that can be altered in asthma, namely regarding oxidative stress and systemic inflammation, and also suggesting the importance of microbiota in asthma pathogenesis. Considering the reduced response to corticosteroids, other pharmacologic treatments have been shown to be effective regardless of body mass index. Non-pharmacologic treatments (namely weight reduction and dietary changes) may bring substantial benefit to the asthmatic patient. Taken together, this evidence points towards the need to improve our knowledge in this filed and, in particular, to address the influence of environmental factors in metabolic dysfunction and asthma development. Personalized medicine is definitely needed to optimize treatment, including a holistic view of the asthmatic patient in order to set accurate pharmacologic therapy together with dietary, physical exercise and lifestyle interventions.

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Mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/body mass index: meta-analysis of MENSA and MUSCA

Cited by 39 publications

References 24 publications

Real-life effectiveness of mepolizumab in patients with severe refractory eosinophilic asthma and multiple comorbidities

Real-life effectiveness of mepolizumab in patients with severe refractory eosinophilic asthma and multiple comorbidities

Effectiveness of mepolizumab in a real-life cohort of patients with severe refractory eosinophilic asthma and multiple comorbidities

<p>Metabolic Dysfunction and Asthma: Current Perspectives</p>

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