Super-Responders to Biologic Treatment in Type 2–High Severe Asthma: Passing Fad or a Meaningful Phenotype?

Portacci, Andrea; Dragonieri, Silvano; Carpagnano, Giovanna Elisiana

doi:10.1016/j.jaip.2023.01.021

Cited by 16 publications

(10 citation statements)

References 25 publications

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“…In patients with SEA only, data reporting baseline symptoms in super-responder patients are discordant. While some evidence suggests that lower baseline ACQ scores could foreshadow a greater response to biologics [ 5 , 6 ], other studies reported different results [ 26 , 27 ]. A possible explanation could be related to higher T0 BEC in super-responders, which could explain their worse baseline clinical status.…”

Section: Discussionmentioning

confidence: 99%

“…However, clinical response to monoclonal antibodies can be heterogeneous, challenging clinicians to define which cluster of patients has the greatest improvement after a course of treatment. As a matter of fact, SEA “super-responders” have been variously defined according to multiple clinical, functional and biological features [ 5 ]. According to current literature, there are two generally accepted criteria to define a super-responder: the lack of asthma exacerbations and the discontinuation of oral corticosteroids (OCS) after ≥12 months of biologic treatment [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Real-world characteristics of “super-responders” to mepolizumab and benralizumab in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis

Portacci,

Campisi,

Buonamico

et al. 2023

ERJ Open Res

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BackgroundCurrent definition of Severe Eosinophilic Asthma (SEA) Super-Responders (SR) to biologic treatment does not include patients with other eosinophils-based comorbidities. Whereas Eosinophilic Granulomatosis with Polyangitis (EGPA) is frequently associated with SEA, we lack data on a possible super-response to biologic treatments in patients suffering from these two diseases. We aim to assess SR features in real-life patients with SEA and EGPA treated with Mepolizumab and Benralizumab.MethodsWe enrolled 39 patients with SEA and EGPA eligible to treatment with Mepolizumab or Benralizumab. SR assessment was performed considering OCS cessation, the lack of exacerbations, FEV1 and ACT improvement.ResultsSR showed worse clinical baseline characteristics than non-SR patients, with a greater improvement in severe asthma exacerbations, OCS dose reduction and ACT score increase. Definition of SR was consistent only considering a 12-months course of monoclonal antibody, lacking sensitivity in earlier evaluations.ConclusionMepolizumab and Benralizumab are safe and effective in patients with EGPA and SEA, since a consistent part of patients show a super-response after 12 months of treatment. Further studies will address specific criteria for SR assessment in these patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Real-world characteristics of “super-responders” to mepolizumab and benralizumab in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis

Portacci,

Campisi,

Buonamico

et al. 2023

ERJ Open Res

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“…The timely improvement in respiratory function and other observed remission features strongly indicate that these therapies have a fast-acting potential in inducing severe asthma CliR. As previously postulated, the path leading to CliR seems to follow a specific timeline since a real difference in main asthma clinical items (exacerbations, OCS, symptoms) between remittent and non-remittent patients becomes clinically visible only after at least 3 months of biologic therapy ( 17 ). Moreover, lung function improvement seems to be affected by biologic therapies earlier than other clinical features.…”

Section: Discussionmentioning

confidence: 82%

Features of severe asthma response to anti-IL5/IL5r therapies: identikit of clinical remission

Carpagnano,

Portacci,

Nolasco

et al. 2024

Front. Immunol.

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IntroductionClinical remission (CliR) achievement has been recognized as a new potential outcome in severe asthma. Nevertheless, we still lack a detailed profile of what features could better identify patients undergoing clinical remission. In this study, we aim to address this issue, tracing a possible identikit of patients fulfilling remission criteria.MethodsWe enrolled 266 patients with severe eosinophilic asthma (SEA) treated with a 12-month course of anti-IL5/IL5 receptor (IL5r) monoclonal antibodies. Patients with no exacerbation, OCS withdrawal, ACT ≥ 20 and FEV1 ≥ 80% after 1 year of biologic treatment were classified as in clinical remission.Results30.5% of the enrolled patients achieved remission after biologic administration. CliR group showed a lower number of baseline asthma exacerbations and better lung function parameters, with a trend for higher ACT scores and a less frequent history of a positive skin prick test. CliR achievement was unlikely in presence of a higher BMI, a positive skin prick test, an increased number of asthma exacerbations before biologic treatment, anti-muscarinic administration, and a previous diagnosis of EGPA, bronchiectasis or osteoporosis. In contrast, a better lung function, an increased blood eosinophilic count, the presence of chronic rhinosinusitis with nasal polyps and a more frequent use of reliever therapy predicts remission development. Changes in exacerbations number, OCS use, ACT scores and FEV1% between remittent and non-remittent patients arise at specific follow up timepoints and are positively associated with CliR achievement.Discussionanti-IL5/IL5r biologics can induce CliR in a proportion of patients with SEA. Patients achieving remission demonstrate specific clinical, functional and inflammatory features, as well as a specific moment of improvement in all the CliR items.

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“…Recent evidence has identified a new phenotype, super-responders, for patients taking biologic treatments. Super responders are defined by a group of patients with a more rapid response to a certain treatment leading to better asthma control and quality of life ( Portacci et al, 2023 ). The super responder rate is estimated to be between 14% and 44% and more commonly is observed in patients with male sex, no smoking history, a lower BMI, higher T2 biomarker levels, and a later age of disease onset ( Jane McDowell et al, 2023 ; Portacci et al, 2023 ).…”

Section: Biological Therapies In Type-2 High Asthmamentioning

confidence: 99%

“…Super responders are defined by a group of patients with a more rapid response to a certain treatment leading to better asthma control and quality of life ( Portacci et al, 2023 ). The super responder rate is estimated to be between 14% and 44% and more commonly is observed in patients with male sex, no smoking history, a lower BMI, higher T2 biomarker levels, and a later age of disease onset ( Jane McDowell et al, 2023 ; Portacci et al, 2023 ). Obesity influences potential for asthma remission on biological therapies, with a 47% lower frequency of remission in patients with obesity compared to patients without obesity ( Jane McDowell et al, 2023 ).…”

Section: Biological Therapies In Type-2 High Asthmamentioning

confidence: 99%

Effects of biological therapies on patients with Type-2 high asthma and comorbid obesity

Garg,

Que,

Ingram

2024

Front. Pharmacol.

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Over 20 million adults and 6 million children in the United States (US) have asthma, a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, and mucus hypersecretion. Obesity, another highly prevalent disease in the US, is a major risk factor for asthma and a significant cause of diminished asthma control, increased submucosal eosinophilia, and reduced quality of life. A large subgroup of these patients experiences severe symptoms and recurrent exacerbations despite maximal dosage of standard asthma therapies. In the past two decades, the development of biological therapies has revolutionized the field and advanced our understanding of type 2 inflammatory biomarkers. However, patients with obesity and comorbid asthma are not principally considered in clinical trials of biologics. Large landmark cluster analyses of patients with asthma have consistently identified specific asthma phenotypes that associate with obesity but may be differentiated by age of asthma onset and inflammatory cell profiles in sputum. These patterns suggest that biologic processes driving asthma pathology are heterogenous among patients with obesity. The biological mechanisms driving pathology in patients with asthma and comorbid obesity are not well understood and likely multifactorial. Future research needs to be done to elicit the cellular and metabolic functions in the relationship of obesity and asthma to yield the best treatment options for this multiplex condition. In this review, we explore the key features of type 2 inflammation in asthma and discuss the effectiveness, safety profile, and research gaps regarding the currently approved biological therapies in asthma patients with obesity.

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Super-Responders to Biologic Treatment in Type 2–High Severe Asthma: Passing Fad or a Meaningful Phenotype?

Cited by 16 publications

References 25 publications

Real-world characteristics of “super-responders” to mepolizumab and benralizumab in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis

Real-world characteristics of “super-responders” to mepolizumab and benralizumab in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis

Features of severe asthma response to anti-IL5/IL5r therapies: identikit of clinical remission

Effects of biological therapies on patients with Type-2 high asthma and comorbid obesity

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