Severe refractory asthma: current treatment options and ongoing research

Menzella, Francesco; Bertolini, Francesca; Biava, Mirella; Galeone, Carla; Scelfo, Chiara; Caminati, Marco

doi:10.7573/dic.212561

Cited by 26 publications

(22 citation statements)

References 111 publications

(117 reference statements)

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“… 12 In fact, those who had experience with anti-IL5 therapy did not think that any of the anti-IL5 medications were superior to the others, but they preferred a more precision-based approach for each patient. 27 , 28 More interestingly, doctors with previous anti-IL5 experience did not believe that switching to another anti-IL5 following an incomplete response to anti-IL5 treatment would be beneficial, despite some conflicting evidence. 15 Those with previous anti-IL5 experience were confident that anti-IL5 drugs can be beneficial in concomitant nasal polyposis and, in fact, a recent review concluded that omalizumab, mepolizumab, and reslizumab are effective in improving nasal polyposis.…”

Section: Discussionmentioning

confidence: 99%

Beliefs and preferences regarding biological treatments for severe asthma

Bikov

Oğuzülgen

Baiardini

et al. 2020

World Allergy Organization Journal

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Background Severe asthma is a serious condition with a significant burden on patients' morbidity, mortality, and quality of life. Some biological therapies targeting the IgE and interleukin-5 (IL5) mediated pathways are now available. Due to the lack of direct comparison studies, the choice of which medication to use varies. We aimed to explore the beliefs and practices in the use of biological therapies in severe asthma, hypothesizing that differences will occur depending on the prescribers’ specialty and experience. Methods We conducted an online survey composed of 35 questions in English. The survey was circulated via the INterasma Scientific Network (INESNET) platform as well as through social media. Responses from allergists and pulmonologists, both those with experience of prescribing omalizumab with (OMA/IL5) and without (OMA) experience with anti-IL5 drugs, were compared. Results Two hundred eighty-five (285) valid questionnaires from 37 countries were analyzed. Seventy-on percent (71%) of respondents prescribed biologics instead of oral glucocorticoids and believed that their side effects are inferior to those of Prednisone 5 mg daily. Agreement with ATS/ERS guidelines for identifying severe asthma patients was less than 50%. Specifically, significant differences were found comparing responses between allergists and pulmonologists (Chi-square test, p < 0.05) and between OMA/IL5 and OMA groups (p < 0.05). Conclusions Uncertainties and inconsistencies regarding the use of biological medications have been shown. The accuracy of prescribers to correctly identify asthma severity, according to guidelines criteria, is quite poor. Although a substantial majority of prescribers believe that biological drugs are safer than low dose long-term treatment with oral steroids, and that they must be used instead of oral steroids, every effort should be made to further increase awareness. Efficacy as disease modifiers, biomarkers for selecting responsive patients, timing for outcomes evaluation, and checks need to be addressed by further research. Practices and beliefs regarding the use of asthma biologics differ between the prescriber's specialty and experience; however, the latter seems more significant in determining beliefs and behavior. Tailored educational measures are needed to ensure research results are better integrated in daily practice.

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Section: Discussionmentioning

confidence: 99%

Beliefs and preferences regarding biological treatments for severe asthma

Bikov

Oğuzülgen

Baiardini

et al. 2020

World Allergy Organization Journal

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“…Furthermore, even in patients with fixed airflow obstruction and obesity, a significant improvement of lung function has been observed during benralizumab treatment course 38. Benralizumab also demonstrated a greater steroid-sparing effect in comparison with other anti IL-5 drugs 4…”

Section: Target Population: Potential Predictors Of Efficacymentioning

confidence: 93%

“…Eosinophilic asthma is a relevant subtype of asthma associated with increased risk of severe exacerbations and a difficult control, despite high doses of oral and inhaled corticosteroids. In the last decades, that asthma phenotype has been extensively explored, and the increasing evidence concerning the underlying inflammation mechanisms has highlighted new potential therapeutic targets and subsequently has paved the way to new selective drugs 4. In the next few years further biologic and bio-similar molecules selectively addressing eosinophils and Th2 inflammation will become available on the market, substantially enlarging the treatment options for the patients with severe eosinophilic asthma 4.…”

Section: Introductionmentioning

confidence: 99%

“…In the last decades, that asthma phenotype has been extensively explored, and the increasing evidence concerning the underlying inflammation mechanisms has highlighted new potential therapeutic targets and subsequently has paved the way to new selective drugs 4. In the next few years further biologic and bio-similar molecules selectively addressing eosinophils and Th2 inflammation will become available on the market, substantially enlarging the treatment options for the patients with severe eosinophilic asthma 4. On the other hand, the lack of biomarkers specifically predicting the good clinical response to each biologic, which is currently a potential limitation in the field, may hamper the selection of the right drug for the right patient 5.…”

Section: Introductionmentioning

confidence: 99%

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<p>New horizons for the treatment of severe, eosinophilic asthma: benralizumab, a novel precision biologic</p>

Caminati

Bagnasco

Vaia

et al. 2019

BTT

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In the last decades, the increasing evidence concerning inflammation mechanisms underlying severe eosinophilic asthma has highlighted new potential therapeutic targets and has paved the way to new selective biologic drugs. Understanding the mechanism of action and the clinical outcomes of a particular drug along with the clinical and biological characteristics of the patient population for which that drug was intended may ensure appropriate selection of patients that will respond to that drug. Under this perspective, the present review will focus on the mechanisms of action and clinical evidence of benralizumab as a treatment option for severe eosinophilic asthma, in order to provide a concise overview and a reference for clinical practice. Benralizumab is a fully humanized afucosylated IgG1κ mAb that binds to an epitope on IL-5 Rα, and inhibits IL-5 signaling. Benralizumab also sustains antibody-directed cell-mediated cytotoxicity (ADCC) of eosinophils and basophils and consequently depletes IL-5Rα-expressing cells. As a result, it is responsible for a substantial depletion of blood, tissue, and bone marrow eosinophilia. This unique mechanism of action may account for a more complete and rapid action profile. Randomized clinical trials have demonstrated that benralizumab provides an optimal safety profile, and is able to significantly reduce asthma exacerbations, oral steroid intake, and to improve lung function. Some clinical predictors of enhanced clinical response to benralizumab have also been identified, including: a level of blood eosinophils ≥300 μL −1 , oral steroids use, the presence of nasal polyposis, FVC <65% of predicted, and a history of three or more exacerbations per year at baseline. These results can be helpful in identifying the best responder patients to benralizumab. As a step forward, the definition of the responder profile for each of the available biological treatment options will potentially support even more the pathway to precision medicine and the critical matching of the right drug with the right patient.

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“…Omalizumab, a monoclonal antibody (mAb) that specifically targets IgE, was the first mAb approved for the treatment of severe asthma, in a specific subpopulation of patients with uncontrolled IgE-mediated allergic asthma. Recently, new options, such as anti-IL-5 mAbs and anti-IL-4/IL-13, are available or will be in the near future 11. Asthma is increasingly recognized as a syndrome with similar clinical presentations rather than a single disease.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and steroid-sparing effect of benralizumab: has it an advantage over its competitors?

Menzella¹,

Biava

Bagnasco

et al. 2019

DIC

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Severe refractory asthma is characterized by a higher risk of asthma-related symptoms, morbidities, and exacerbations. This disease also determines much greater healthcare costs and deterioration in health-related quality of life (HR-QoL). Another concern, which is currently much discussed, is the high percentage of patients needing regular use of oral corticosteroids (OCS), which can lead to several systemic side effects. Airway eosinophilia is present in the majority of asthmatic patients, and elevated levels of blood and sputum eosinophils are associated with worse control of asthma. Regarding severe refractory eosinophilic asthma, interleukin-5 (IL-5) plays a fundamental role in the inflammatory response, due to the profound effect on eosinophils biology. The advent of the biological therapies provided an effective strategy, even if the increased number of molecules with different targets raised the challenge of choosing the right therapy and avoid overlapping. When considering severe refractory eosinophilic asthma and anti-IL-5 treatments, it is not easy to define which drug to choose between mepolizumab, reslizumab, and benralizumab. In this article, we carried out an indirect comparison among literature data, especially between OCS reduction studies (ZONDA-SIRIUS) and pivotal studies (SIROCCO-MENSA), evaluating whether the clinical efficacy and the steroid-sparing effect of benralizumab may represent an advantage over other compounds. This data could help the clinician in the decision process of treatment choice, within the different available therapeutic options for eosinophilic refractory severe asthma.

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Severe refractory asthma: current treatment options and ongoing research

Cited by 26 publications

References 111 publications

Beliefs and preferences regarding biological treatments for severe asthma

Beliefs and preferences regarding biological treatments for severe asthma

<p>New horizons for the treatment of severe, eosinophilic asthma: benralizumab, a novel precision biologic</p>

Efficacy and steroid-sparing effect of benralizumab: has it an advantage over its competitors?

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