Biologic Therapies for Severe Asthma

2022 ◽  
Vol 386 (2) ◽  
pp. 157-171
Author(s):  
Guy G. Brusselle ◽  
Gerard H. Koppelman
Keyword(s):  
Severe Asthma ◽  
Biologic Therapies

Applying personalized medicine to adult severe asthma

2021 ◽  
Vol 42 (1) ◽  
pp. e8-e16 ◽  
Author(s):  
Angelica Tiotiu
Keyword(s):  
Personalized Medicine ◽  
Severe Asthma ◽  
Negative Impact ◽  
Target Therapy ◽  
Asthma Management ◽  
Future Research ◽  
Biologic Therapies ◽  
Eosinophilic Asthma ◽  
Definition Of ◽  
Structured Approach

Background: Severe asthma is a heterogeneous disease that consists of various phenotypes driven by different pathways. Associated with significant morbidity, an important negative impact on the quality of life of patients, and increased health care costs, severe asthma represents a challenge for the clinician. With the introduction of various antibodies that target type 2 inflammation (T2) pathways, severe asthma therapy is gradually moving to a personalized medicine approach. Objective: The purpose of this review was to emphasize the important role of personalized medicine in adult severe asthma management. Methods: An extensive research was conducted in medical literature data bases by applying terms such as “severe asthma” associated with “structured approach,” “comorbidities,” “biomarkers,” “phenotypes/endotypes,” and “biologic therapies.” Results: The management of severe asthma starts with a structured approach to confirm the diagnosis, assess the adherence to medications and identify confounding factors and comorbidities. The definition of phenotypes or endotypes (phenotypes defined by mechanisms and identified through biomarkers) is an important step toward the use of personalized medicine in asthma. Severe allergic and nonallergic eosinophilic asthma are two defined T2 phenotypes for which there are efficacious targeted biologic therapies currently available. Non-T2 phenotype remains to be characterized, and less efficient target therapy exists. Conclusion: Despite important progress in applying personalized medicine to severe asthma, especially in T2 inflammatory phenotypes, future research is needed to find valid biomarkers predictive for the response to available biologic therapies to develop more effective therapies in non-T2 phenotype.

scholarly journals Clinical and economic burden of severe asthma among US patients treated with biologic therapies

2021 ◽  
Author(s):  
Joan Reibman ◽  
Laren Tan ◽  
Chris Ambrose ◽  
Yen Chung ◽  
Pooja Desai ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Economic Burden ◽  
Biologic Therapies

scholarly journals Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-215168
Author(s):  
David J Jackson ◽  
John Busby ◽  
Paul E Pfeffer ◽  
Andrew Menzies-Gow ◽  
Thomas Brown ◽  
...  
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Symptom Control ◽  
Unmet Need ◽  
High Dose ◽  
Blood Eosinophil ◽  
Biologic Therapies ◽  
Exacerbation Rate ◽  
The Uk ◽  
Blood Eosinophils

BackgroundThe UK Severe Asthma Registry (UKSAR) is the world’s largest national severe asthma registry collecting standardised data on referrals to UK specialist services. Novel biologic therapies have transformed the management of type 2(T2)-high severe asthma but have highlighted unmet need in patients with persisting symptoms despite suppression of T2-cytokine pathways with corticosteroids.MethodsDemographic, clinical and treatments characteristics for patients meeting European Respiratory Society / American Thoracic Society severe asthma criteria were examined for 2225 patients attending 15 specialist severe asthma centres. We assessed differences in biomarker low patients (fractional exhaled nitric oxide (FeNO) <25 ppb, blood eosinophils <150/μL) compared with a biomarker high population (FeNO ≥25 ppb, blood eosinophils ≥150/µL).ResultsAge (mean 49.6 (14.3) y), age of asthma onset (24.2 (19.1) y) and female predominance (62.4%) were consistent with prior severe asthma cohorts. Poor symptom control (Asthma Control Questionnaire-6: 2.9 (1.4)) with high exacerbation rate (4 (IQR: 2, 7)) were common despite high-dose treatment (51.7% on maintenance oral corticosteroids (mOCS)). 68.9% were prescribed biologic therapies including mepolizumab (50.3%), benralizumab (26.1%) and omalizumab (22.6%). T2-low patients had higher body mass index (32.1 vs 30.2, p<0.001), depression/anxiety prevalence (12.3% vs 7.6%, p=0.04) and mOCS use (57.9% vs 42.1%, p<0.001). Many T2-low asthmatics had evidence of a historically elevated blood eosinophil count (0.35 (0.13, 0.60)).ConclusionsThe UKSAR describes the characteristics of a large cohort of asthmatics referred to UK specialist severe asthma services. It offers the prospect of providing novel insights across a range of research areas and highlights substantial unmet need with poor asthma control, impaired lung function and high exacerbation rates. T2-high phenotypes predominate with significant differences apparent from T2-low patients. However, T2-low patients frequently have prior blood eosinophilia consistent with possible excessive corticosteroid exposure.

Lessons learned from clinical trials of asthma

2019 ◽  
Vol 40 (6) ◽  
pp. 410-413
Author(s):  
Paul A. Greenberger
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Immunoglobulin E ◽  
Environmental Control ◽  
Mild Asthma ◽  
Inhaled Corticosteroid ◽  
Biologic Therapies ◽  
Asthma Control Questionnaire ◽  
Exacerbation Rate ◽  
Sputum Eosinophilia

Exacerbations of persistent or intermittent asthma should be anticipated by physicians and health-care professionals. Patients who are likely to experience an exacerbation often have a history of an exacerbation in the previous year, and the absolute eosinophil count in peripheral blood is ≥ 400/μL. Similarly, expectorated or induced sputum eosinophilia of ≥2% is associated with exacerbations. These phenotypic findings have led to effective biologic therapies, which target eosinophils or immunoglobulin E or the T-helper type 2 phenotype, especially in children, adolescents, and adults with frequent exacerbations. In children, a reduced forced expiratory volume in the first second of expiration (FEV1) to forced vital capacity ratio can be associated with future exacerbations, although the FEV1 may be in the normal range, even with children who have persistent severe asthma. Asthma control questionnaires did not differentiate between children with or children without a future exacerbation. Alternatively, in adults, the lower baseline FEV1 (2.3 L [74% predicted] versus 2.5 L [78% predicted]) identified patients more likely to have a future exacerbation compared with patients who were not having an exacerbation. After correcting for FEV1, the asthma control questionnaire data were associated with exacerbations. In adolescents (ages ≥ 12 years) and adults with persistent mild asthma, most (73%) did not have sputum eosinophilia, and some of these patients responded well to the anticholinergic, tiotropium, which would argue differently from administration of an inhaled corticosteroid as first-line controller therapy. In a three-track study of patients with persistent mild asthma, as-needed budesonide-formoterol and scheduled budesonide were associated with approximately one-half of the annual exacerbation rate of as-needed albuterol. In patients with persistent moderate-to-severe asthma, tiotropium added to controller therapy caused an increase in FEV1 without improving the asthma control questionnaire findings. There were two studies that explored whether either quadrupling or quintupling the inhaled corticosteroid at the first sign of loss of control of asthma would provide meaningful reductions of severe exacerbations of asthma, but the findings did not support this strategy. Both biologic therapies and environmental control (dust mite impermeable encasings) have resulted in reductions of exacerbations in patients with persistent moderate and severe asthma.

scholarly journals Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option?

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Michael E. Wechsler ◽  
Chris E. Brightling
Keyword(s):  
Inflammatory Response ◽  
Airway Inflammation ◽  
Asthma Control ◽  
Severe Asthma ◽  
Human Monoclonal Antibody ◽  
Unmet Need ◽  
Blood Eosinophil ◽  
Biologic Therapies ◽  
Uncontrolled Asthma ◽  
Asthma Exacerbations

Abstract Despite treatment with standard-of-care medications, including currently available biologic therapies, many patients with severe asthma have uncontrolled disease, which is associated with a high risk of hospitalization and high healthcare costs. Biologic therapies approved for severe asthma have indications limited to patients with either eosinophilic or allergic phenotypes; there are currently no approved biologics for patients with eosinophil-low asthma. Furthermore, existing biologic treatments decrease exacerbation rates by approximately 50% only, which may be because they target individual, downstream elements of the asthma inflammatory response, leaving other components untreated. Targeting an upstream mediator of the inflammatory response may have a broader effect on airway inflammation and provide more effective asthma control. One such potential target is thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine released in response to multiple triggers associated with asthma exacerbations, such as viruses, allergens, pollutants and other airborne irritants. Mechanistic studies indicate that TSLP drives eosinophilic (including allergic) inflammation, neutrophilic inflammation and structural changes to the airway in asthma through actions on a wide variety of adaptive and innate immune cells and structural cells. Tezepelumab is a first-in-class human monoclonal antibody that blocks the activity of TSLP. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced asthma exacerbations by up to 71% compared with placebo in patients with severe, uncontrolled asthma across the spectrum of inflammatory phenotypes, and improved lung function and asthma control. Phase 3 trials of tezepelumab are underway. NAVIGATOR (NCT03347279), a pivotal exacerbation study, aims to assess the potential efficacy of tezepelumab further in patients with a broad range of severe asthma phenotypes, including those with low blood eosinophil counts. SOURCE (NCT03406078) aims to evaluate the oral corticosteroid-sparing potential of tezepelumab. DESTINATION (NCT03706079) is a long-term extension study. In addition, an ongoing phase 2 bronchoscopy study, CASCADE (NCT03688074), aims to evaluate the effect of tezepelumab on airway inflammation and airway remodelling in patients across the spectrum of type 2 airway inflammation. Here, we summarize the unmet therapeutic need in severe asthma and the current treatment landscape, discuss the rationale for targeting TSLP in severe asthma therapy and describe the current development status of tezepelumab.

Changing Paradigms in the Treatment of Severe Asthma: The Role of Biologic Therapies

2017 ◽  
Vol 5 (2) ◽  
pp. S1-S14 ◽  
Author(s):  
Rohit K. Katial ◽  
Greg W. Bensch ◽  
William W. Busse ◽  
Bradley E. Chipps ◽  
Joshua L. Denson ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Biologic Therapies

scholarly journals Biomarkers in the context of managing severe asthma

2019 ◽  
Vol 2 (1) ◽  
pp. 10-18
Author(s):  
Stanley J. Szefler
Keyword(s):  
Nitric Oxide ◽  
Severe Asthma ◽  
Clinical Application ◽  
Biologic Therapy ◽  
Asthma Management ◽  
Response To Treatment ◽  
Biologic Therapies ◽  
Uncontrolled Asthma ◽  
The Cost ◽  
Blood Eosinophils

Only recently have asthma strategies addressed biomarkers in asthma management, for example, as applied in the identification of severe asthmatics likely to respond to biologic therapy. Three biomarkers are readily available for clinical application in managing severe asthma including blood eosinophils, exhaled nitric oxide and serum IgE. While we have a limited number of biomarkers for clinical application, the available biomarkers have ushered in the era of personalized medicine for asthma. These three biomarkers are readily available for application in the clinic setting to select medications and to monitor response to treatment as well as medication adherence. These biomarkers can be used to modify the cost of uncontrolled asthma and also used to select those patients likely to respond to the available biologic therapies for severe asthma.

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