scholarly journals Severe eosinophilic bronchial asthma: new therapeutic options

2018 ◽  
pp. 44-52 ◽  
Author(s):  
N. M. Nenasheva
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Asthma ◽  
Bronchial Asthma ◽  
Biological Agents ◽  
Therapeutic Options ◽  
Clinical Use ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma

Eosinophilic asthma is a common phenotype of severe asthma, occurring in at least half of patients. In recent years, there have been significant changes in the approaches to the treatment of severe bronchial asthma and, above all, eosinophilic asthma. The article discusses the role of eosinophils in the pathogenesis of severe asthma, the detection of the phenotype of severe eosinophilic asthma, and modern approaches to targeting severe asthma with an eosinophilic phenotype using biological agents. A special emphasis is placed on preparations of monoclonal antibodies to interleukin-5, in particular, mepolizumab, recently approved for clinical use in our country.

scholarly journals Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial

2019 ◽  
Vol 5 (3) ◽  
pp. 00009-2019 ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Jonathan Corren ◽  
Elisabeth H. Bel ◽  
Jorge Maspero ◽  
Liam G. Heaney ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Asthma Control ◽  
Severe Asthma ◽  
Maintenance Phase ◽  
Phase Iii ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Link Type ◽  
Related Quality

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody approved in several countries for the add-on maintenance treatment of patients with severe eosinophilic asthma aged 12 years and older. In the 28-week Phase III ZONDA trial (ClinicalTrials.gov identifier: NCT02075255), benralizumab produced a median 75% reduction from baseline in oral corticosteroid (OCS) dosage (versus 25% for placebo) while maintaining asthma control for patients with OCS-dependent severe asthma. This manuscript presents the detailed protocol for the Phase IIIb PONENTE (ClinicalTrials.gov identifier: NCT03557307), a study that will build on the findings from ZONDA.As the largest steroid-sparing study undertaken in severe asthma, PONENTE has a faster steroid tapering schedule for prednisone dosages ≥7.5 mg·day−1 than previous studies, and it includes an evaluation of adrenal insufficiency and an algorithm to taper OCS dosage when prednisone dosage is ≤5 mg·day−1. It also has a longer maintenance phase to assess asthma control for up to 6 months after completion of OCS tapering.The two primary endpoints are whether patients achieve 100% reduction in daily OCS use and whether patients achieve 100% reduction in daily OCS or achieve OCS dosage ≤5 mg·day−1, if adrenal insufficiency prevented further reduction, both sustained over ≥4 weeks without worsening of asthma. Safety and change from baseline in health-related quality of life will also be assessed.PONENTE should provide valuable guidance for clinicians on tapering OCS dosage, including the management of adrenal insufficiency, following benralizumab initiation for the treatment of patients who are OCS-dependent with severe, uncontrolled eosinophilic asthma.

scholarly journals Severe eosinophilic asthma: therapeutic potential of Reslizumab

2018 ◽  
pp. 70-75
Author(s):  
R. S. Fassakhov
Keyword(s):  
Quality Of Life ◽  
Monoclonal Antibodies ◽  
Therapeutic Potential ◽  
Asthma Prevalence ◽  
Frequency Of Occurrence ◽  
Eosinophilic Inflammation ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma

The review discusses the problems associated with the treatment of patients with severe resistant to therapy asthma: prevalence, socio-economic burden, impact on quality of life. The phenotype of bronchial asthma with eosinophilic inflammation, frequency of occurrence, clinical features, and modern approaches to therapy are discussed in detail, including the use of a drug of monoclonal antibodies against interleukin 5-reslizumab.

scholarly journals The effectiveness of Reslizumab in severe asthma treatment: a real-world experience

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
H. Ibrahim ◽  
R. O’Sullivan ◽  
D. Casey ◽  
J. Murphy ◽  
J. MacSharry ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Asthma Severity ◽  
Oral Steroid ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Prednisolone Dose ◽  
Exacerbation Frequency ◽  
Efficacy Parameters

Abstract Background Increased numbers of blood and sputum eosinophils are associated with higher exacerbation frequency and increased asthma severity. In clinical trials, targeting Interleukin-5 has been shown to be a useful therapeutic strategy for patients with severe eosinophilic asthma. Methods Twenty-six patients have been commenced on Reslizumab in our institution since early 2017. Safety and clinical efficacy parameters were recorded at regular intervals. Results Mean ACQ-6 score at the start of treatment was 3.5. The average number of exacerbations in the year preceding treatment was 8.3 per person. 30% of patients had been admitted to hospital at least once over the 12 months preceding therapy. 54% of our patients were on long term oral steroid. Our data showed sustained improvement of Asthma control (Mean improvement in ACQ-6 was 1.7 at 1 year, and 2.0 at 2 years, P = 0.0001). Of the patients who were on long term systemic steroids, 35.7% discontinued steroids completely, with a mean reduction of prednisolone dose of 5.2 mg at 1 year. There was a 79% reduction in the annual exacerbation frequency at 1 year, and 88% at 2 years (P = < 0.0001). Modest, albeit statistically significant increases in creatine kinase which seemed to plateau by 1 year were noted. Conclusions Overall, Reslizumab was well tolerated with discontinuation of treatment due to side effects recorded in only one patient. Our data confirm the utility of anti-IL5 therapy in a carefully selected phenotype of severe asthma with evidence of eosinophilic airway inflammation.

scholarly journals Severe eosinophilic asthma: from the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab

2017 ◽  
Vol Volume 11 ◽  
pp. 3137-3144 ◽  
Author(s):  
Corrado Pelaia ◽  
Alessandro Vatrella ◽  
Maria Teresa Busceti ◽  
Luca Gallelli ◽  
Rosa Terracciano ◽  
...  
Keyword(s):  
Therapeutic Action ◽  
Pathogenic Role ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma

scholarly journals Successful management of severe bronchial asthma: the right choice of biologic therapy in properly selected patients

2019 ◽  
pp. 22-28
Author(s):  
R. S. Fassakhov
Keyword(s):  
Quality Of Life ◽  
Monoclonal Antibodies ◽  
Severe Asthma ◽  
Bronchial Asthma ◽  
Interleukin 5 ◽  
Leading Role ◽  
The Difference ◽  
The Right ◽  
The Impact

Severe asthma along with the impact on the quality of life of those suffering from this disease leads to significant medical and social damage. Studies of the last decade indicate the leading role of eosinophilic inflammation of the bronchi as the basis of the pathogenesis of the T2 phenotype of bronchial asthma, which led to the development of targeted therapy. The most effective in this direction were preparations of humanized monoclonal antibodies directed against the main pro-inflammatory cytokines involved in respiratory tract inflammation in bronchial asthma, one of the most significant among which is interleukin 5. Refinement of the definition of severe asthma, selection of these patients among patients with difficult to treat bronchial asthma allows to clearly determine the contingent with a predicted positive effect these highly effective drugs precision therapy. On clinical examples, the difference between difficult to treat and severe bronchial asthma is discussed. The stages of clinical trials of the preparation of monoclonal antibodies against interleukin 5 Mepolizumab are analyzed in detail, the search for effective prognostic biological markers available in normal practice, allowing to select patients suitable for the treatment of patients with severe eosinophilic bronchial asthma. The effectiveness of the approach based on the allocation of two threshold values of the number of eosinophils in the peripheral blood is convincingly confirmed by the results indicating a significant reduction in the number of exacerbations, improved of lung function and an increase of the quality of life in patients, including with steroiddependent bronchial asthma, obtained not only in randomized clinical studies, but also in studies in real clinical practice.

scholarly journals Severe Eosinophilic Asthma

2019 ◽  
Vol 8 (9) ◽  
pp. 1375 ◽  
Author(s):  
Bakakos ◽  
Loukides ◽  
Bakakos
Keyword(s):  
Quality Of Life ◽  
Severe Asthma ◽  
Airway Remodeling ◽  
Severe Case ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Medication Side ◽  
The Right

Asthma is a heterogeneous disease with varying severity. Severe asthma is a subject of constant research because it greatly affects patients’ quality of life, and patients with severe asthma experience symptoms, exacerbations, and medication side effects. Eosinophils, although at first considered insignificant, were later specifically associated with features of the ongoing inflammatory process in asthma, particularly in the severe case. In this review, we discuss new insights into the pathogenesis of severe asthma related to eosinophilic inflammation and the pivotal role of cytokines in a spectrum that is usually referred to as “T2-high inflammation” that accounts for almost half of patients with severe asthma. Recent literature is summarized as to the role of eosinophils in asthmatic inflammation, airway remodeling, and airway hypersensitivity. Major advances in the management of severe asthma occurred the past few years due to the new targeted biological therapies. Novel biologics that are already widely used in severe eosinophilic asthma are discussed, focusing on the choice of the right treatment for the right patient. These monoclonal antibodies primarily led to a significant reduction of asthma exacerbations, as well as improvement of lung function and patient quality of life.

scholarly journals Precision medicine applications for severe asthma

2019 ◽  
Vol 6 (4) ◽  
pp. 117-135
Author(s):  
Orit Gourgy Hacohen ◽  
Shai Cohen
Keyword(s):  
Precision Medicine ◽  
Severe Asthma ◽  
Oral Corticosteroid ◽  
Treatment Options ◽  
Current Evidence ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Beneficial Effects ◽  
New Treatment

Asthma is a heterogeneous condition in which multiple pathological pathways manifest with similar symptoms. Severe asthma (SA) is challenging to manage and comprises a significant health and economic burden. Many studies have been conducted in an attempt to define different clinical phenotypes that translate into biological endotypes, with the goal of tailoring treatment based on precision medicine. This review summarizes the current evidence for the treatments of SA, and in particular, the biologic treatments that are currently available: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. We found only limited high-quality direct evidence regarding treatment with anti-IgE (omalizumab) in SA patients. Data regarding anti-interleukin (IL)-5 (mepolizumab, reslizumab and benralizumab) showed beneficial effects in severe eosinophilic asthma (SEA) with different levels of blood eosinophils used in clinical trials. Dupilumab, anti-IL-4/IL-13, was shown to be effective in SEA and is the only agent currently FDA-approved for the indication of oral corticosteroid dependent asthma, regardless of the blood eosinophil level. This review also summarizes the existing knowledge regarding the characteristics of the patient who may respond to the different therapies. As of today, more studies are needed to better understand the diverse mechanisms that underlie SA phenotypes. We have not yet adequately reached the goal of precision medicine. Additional studies are necessary in order to find novel surrogate markers that can predict the response to a specific biologic therapy, especially in patients who are oral corticosteroid dependent. In addition, efforts must be invested into research looking for new treatment options for patients with non-type-2 inflammation SA. Statement of novelty: we review the current evidence regarding tailored treatment therapies in SA, with a particular focus on the knowledge regarding patient selection for specific biologic treatments.

Biologics for oral corticosteroid-dependent asthma

2020 ◽  
Vol 41 (3) ◽  
pp. 151-157
Author(s):  
İnsu Yılmaz
Keyword(s):  
Severe Asthma ◽  
Oral Corticosteroid ◽  
Real Life ◽  
Severe Atopic Dermatitis ◽  
Double Blind ◽  
Eosinophilic Asthma ◽  
Asthma Phenotype ◽  
Severe Eosinophilic Asthma ◽  
Term Administration

Background: Oral corticosteroid (OCS) dependent asthma is one of the severe asthma phenotypes that requires personalized treatment. Objective: To review the role of biologic treatments in OCS-dependent asthma. Methods: A nonsystematic review was performed of emerging multiple novel biologics for potential treatment of OCS-dependent asthma. Results: The serious adverse effects of OCS can be seen as a result of their regular long-term administration. Anti‐interleukin (IL) 5 (mepolizumab), anti‐IL-5R (benralizumab), and anti‐IL-4Rα (dupilumab) are the therapies of choice for OCS-dependent severe asthma. Results of studies showed the efficacy of mepolizumab, benralizumab, and dupilumab, especially in patients with the OCS-dependent severe eosinophilic asthma phenotype and with nasal polyps. Dupilumab may be the therapy of choice of monoclonal antibodies in cases of moderate-severe atopic dermatitis accompanied by OCS-dependent severe asthma. For reslizumab and omalizumab, placebo controlled double-blind studies conducted with OCS-dependent patient populations are needed. Conclusion: Biologics are effective in the “OCS-dependent asthma” phenotype as add-on therapy. It seems that chronic OCS use in OCS-dependent asthma will be replaced by biologic agents that specifically target type 2 inflammation, along with a much better safety profile. However, real-life studies that compare these biologics in OCS-dependent severe asthma are urgently needed.

scholarly journals Efficacy of mepolizumab for patients with severe asthma and eosinophilic chronic rhinosinusitis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Takanori Numata ◽  
Katsutoshi Nakayama ◽  
Hirofumi Utsumi ◽  
Kenji Kobayashi ◽  
Haruhiko Yanagisawa ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Severe Asthma ◽  
Predictive Factors ◽  
Systemic Corticosteroid ◽  
Multivariate Logistic Regression Analysis ◽  
Patient Characteristics ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Eosinophilic Chronic Rhinosinusitis

Abstract Background Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice. Objective To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma. Methods From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations. Results The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [− 71.3 ± 37.0% vs − 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [− 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5–336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14). Conclusion Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.

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