Factors reducing omalizumab response in severe asthma

Sposato, Bruno; Scalese, Marco; Milanese, Manlio; Masieri, Simonetta; Cavaliere, Carlo; Latorre, Manuela; Scichilone, Nicola; Matucci, Andrea; Vultaggio, Alessandra; Rícci, Alberto; Cresti, Alberto; Santus, Pierachille; Perrella, Antonio; Paggiaro, Pierluigi

doi:10.1016/j.ejim.2018.01.026

Cited by 50 publications

(40 citation statements)

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“…Several novel biologic treatments approved for use in patients with differing severe asthma phenotypes have demonstrated reduced efficacy in patients who are obese. For example, a recent retrospective study in patients with severe asthma ( N = 340) found that obesity may reduce the effectiveness of the anti-immunoglobulin E mAb omalizumab, independent of other asthma-influencing factors [15]. In addition, a post hoc pooled analysis of the Phase 3 SIROCCO and CALIMA trials demonstrated that the effects of the anti-IL-5 receptor mAb benralizumab on the annual rate of exacerbations and lung function in patients with severe eosinophilic asthma were less robust in obese individuals than in those who were of normal weight [16].…”

Section: Discussionmentioning

confidence: 99%

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

Albers¹,

Papi

Taillé

et al. 2019

Respir Res

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Background We assessed the efficacy of the licensed mepolizumab dose (100 mg subcutaneously [SC]) in patients with severe eosinophilic asthma according to body weight/body mass index (BMI). Methods This was a post hoc individual patient-level meta-analysis of data from the Phase 3 studies MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318). Patients aged ≥12 years with severe eosinophilic asthma and a history of exacerbations were randomised to 4-weekly placebo, mepolizumab 75 mg intravenously (IV) or 100 mg SC (MENSA) or placebo or mepolizumab 100 mg SC (MUSCA) for 32 (MENSA) or 24 (MUSCA) weeks. The primary endpoint was the annual rate of clinically significant exacerbations; other outcomes included the proportion of patients with no exacerbations, lung function, St George’s Respiratory Questionnaire (SGRQ) and Asthma Control Questionnaire-5 (ACQ-5) scores and blood eosinophil counts. Analyses were performed by baseline body weight and BMI (≤60, > 60–75, > 75–90, > 90, < 100, ≥100 kg; ≤25, > 25–30, > 30, < 36, ≥36 kg/m 2 ). Results Overall, 936 patients received placebo or mepolizumab 100 mg SC. Across all body weight/BMI categories, mepolizumab reduced the rate of clinically significant exacerbations by 49–70% versus placebo. Improvements with mepolizumab versus placebo were also seen in lung function in all body weight/BMI categories except > 90 kg; improvements in SGRQ and ACQ-5 scores were seen across all categories. Conclusions Mepolizumab 100 mg SC has consistent clinical benefits in patients with severe eosinophilic asthma across a range of body weights and BMIs. Data show that the fixed-dose regimen of mepolizumab is suitable, without the need for weight-based dosing. Trial registration This manuscript is a post hoc meta-analysis of data from the Phase 3 studies MENSA and MUSCA. ClinicalTrials.gov, NCT01691521 (MEA115588; MENSA). Registered September 24, 2012. ClinicalTrials.gov, NCT02281318 (200862; MUSCA). Registered November 3, 2014. Electronic supplementary material The online version of this article (10.1186/s12931-019-1134-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

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

Albers¹,

Papi

Taillé

et al. 2019

Respir Res

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“…However, a recent study on factors associated with omalizumab response suggested that obesity (versus normal weight) is a determinant condition for unchanged/increased level of concomitant asthma medication. 76 This has not been confirmed by others. 75 Data comparing regular corticosteroid-sparing effect of all available monoclonal antibodies in obese versus non-obese severe asthmatics is lacking.…”

Section: Literature Review and Discussionmentioning

confidence: 70%

“…Regarding the currently available biologic treatments approved for asthma, the anti-immunoglobulin E (IgE) antibody omalizumab has significantly reduced asthma exacerbations and improved asthma control in obese patients with severe allergic persistent asthma, 75 but obesity may reduce the effectiveness of this monoclonal antibody. 76 Interestingly, a supervised cluster analysis has suggested that the subgroup of asthmatic patients that benefited the most from the more recently approved anti-IL-5 monoclonal antibody mepolizumab is characterized by raised blood eosinophils, obesity and a mean duration of disease of 18 years, which could thus represent the early-onset type 2 obese-asthmatic patients. 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.…”

Section: Literature Review and Discussionmentioning

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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“…Moreover, use of omalizumab and reslizumab is limited with respect to obese patients, since their doses are adjusted for weight [38]. In this sense, a very recent retrospective real-life study suggests that obesity is a risk factor for the lack of response to omalizumab [75].…”

Section: How Obese Asthma Patients Respond To Pharmacological Therapymentioning

confidence: 99%

Obesity and Asthma: Key Clinical Questions

García‐Río¹,

Alvarez-Puebla²,

Esteban-Gorgojo³

et al. 2019

J Investig Allergol Clin Immunol

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Obesity is an asthma common comorbidity and is associated not only with its development, but also with a poorer control and higher severity of it. Recent prospective evidence supports the idea that body weight gain precedes the development of asthma, but the debate is far from over. The objective of this document is to conduct a systematic review of 3 clinical questions related to asthma and obesity: 1. Obesity and asthma: the chicken or the egg? Clinical insights from epidemiological and phenotypes studies. 2. Is obesity a confounding factor in the diagnosis and management of asthma and especially in severe or difficult-to-control asthma? 3. How obese asthma subjects respond to pharmacological treatments, and to biological drugs? Do we have effective specific interventions?. Revised epidemiological, pathological and mechanistic evidence combined with data from the intervention clinical trials do not allow us to clearly state that obesity is an asthma-causative agent. However, the complexity and heterogeneity of these two illnesses make several clinical scenarios possible. Furthermore, the diagnosis of asthma in an obese patient represents an additional clinical challenge. Physicians need to be aware of the confounding effects created by the greater symptomatic perception, the alterations of lung function and the different comorbidities that the obese subjects present. A exhaustive phenotyping of the obese asthma patient should lead us to a rational therapeutic plan, including both, the pharmacological approach and anti-obesity specific therapies including a combined plan of diet and exercise and in extreme cases, bariatric surgery.

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Factors reducing omalizumab response in severe asthma

Cited by 50 publications

References 49 publications

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

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

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

Obesity and Asthma: Key Clinical Questions

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