scholarly journals The Role of Omalizumab in the Treatment of Severe Allergic Asthma

2006 ◽  
Vol 13 (suppl b) ◽  
pp. 1B-9B ◽  
Author(s):  
Kenneth R Chapman ◽  
Andre Cartier ◽  
Jacques Hébert ◽  
R Andrew McIvor ◽  
R Robert Schellenberg
Keyword(s):  
Severe Asthma ◽  
Adjunctive Therapy ◽  
Conventional Therapy ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
Severe Disease ◽  
Phase Iii ◽  
High Dose ◽  
Two Phase ◽  
Long Acting

BACKGROUND: A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.OBJECTIVE: To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.METHODS: A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use.RESULTS: Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or fourweek intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumabtreated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment.RECOMMENDATIONS: Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.

scholarly journals The Role of Omalizumab in the Treatment of Severe Allergic Asthma

2006 ◽  
Vol 13 (suppl b) ◽  
pp. 1B-9B ◽  
Author(s):  
Kenneth R Chapman ◽  
Andre Cartier ◽  
Jacques Hébert ◽  
R Andrew McIvor ◽  
R Robert Schellenberg
Keyword(s):  
Severe Asthma ◽  
Adjunctive Therapy ◽  
Conventional Therapy ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
Severe Disease ◽  
Phase Iii ◽  
High Dose ◽  
Two Phase ◽  
Long Acting

BACKGROUND: A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.OBJECTIVE: To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.METHODS: A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use.RESULTS: Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or fourweek intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumab-treated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment.RECOMMENDATIONS: Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.

Diagnosis and Management of Severe Asthma

2018 ◽  
Vol 39 (01) ◽  
pp. 091-099 ◽  
Author(s):  
Kian Fan Chung
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
High Dose ◽  
Blood Eosinophil ◽  
Exhaled Breath ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Asthma Patients ◽  
Long Acting

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

scholarly journals Canadian Thoracic Society Asthma Management Continuum – 2010 Consensus Summary for Children Six Years of Age and Over, and Adults

2010 ◽  
Vol 17 (1) ◽  
pp. 15-24 ◽  
Author(s):  
M Diane Lougheed ◽  
Catherine Lemière ◽  
Sharon D Dell ◽  
Francine M Ducharme ◽  
J Mark FitzGerald ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
Action Plan ◽  
Age Groups ◽  
Asthma Management ◽  
Accurate Diagnosis ◽  
Objective Measures ◽  
High Dose ◽  
Adult Asthma ◽  
Long Acting

BACKGROUND/OBJECTIVE: To integrate new evidence into the Canadian Asthma Management Continuum diagram, encompassing both pediatric and adult asthma.METHODS: The Canadian Thoracic Society Asthma Committee members, comprised of experts in pediatric and adult respirology, allergy and immunology, emergency medicine, general pediatrics, family medicine, pharmacoepidemiology and evidence-based medicine, updated the continuum diagram, based primarily on the 2008 Global Initiative for Asthma guidelines, and performed a focused review of literature pertaining to key aspects of asthma diagnosis and management in children six years of age and over, and adults.RESULTS: In patients six years of age and over, management of asthma begins with establishing an accurate diagnosis, typically by supplementing medical history with objective measures of lung function. All patients and caregivers should receive self-management education, including a written action plan. Inhaled corticosteroids (ICS) remain the first-line controller therapy for all ages. When asthma is not controlled with a low dose of ICS, the literature supports the addition of long-acting beta2-agonists in adults, while the preferred approach in children is to increase the dose of ICS. Leukotriene receptor antagonists are acceptable as second-line monotherapy and as an alternative add-on therapy in both age groups. Anti-immunoglobulin E therapy may be of benefit in adults, and in children 12 years of age and over with difficult to control allergic asthma, despite high-dose ICS and at least one other controller.CONCLUSIONS: The foundation of asthma management is establishing an accurate diagnosis based on objective measures (eg, spirometry) in individuals six years of age and over. Emphasis is placed on the similarities and differences between pediatric and adult asthma management approaches to achieve asthma control.

scholarly journals Bronchial Thermoplasty in the Treatment of Severe Asthma

2020 ◽  
pp. 1-9
Author(s):  
Nightingale Syabbalo ◽  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Airway Disease ◽  
Airflow Limitation ◽  
Response To Treatment ◽  
High Dose ◽  
Eosinophilic Asthma ◽  
Bronchial Thermoplasty ◽  
Long Acting ◽  
Refractory Asthma

Asthma is a chronic inflammatory airway disease with several distinct phenotypes, characterized by different immunopathological pathways, clinical presentation, severity of the disease, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma. Approximately 3.6-10% of patients with asthma have severe refractory disease, which is unresponsive to high dose inhaled corticosteroids (ICS), and long-acting β2-agonists (LABA). Most patients with eosinophilic asthma are responsive to corticosteroids, and interleukintargeted biologics, whereas, patients from other phenotypes, such as neutrophillic and paucigranullocytic asthma are resistant to treatment with ICS and biotherapeutics. The hallmark of severe refractory asthma is airway hyperresponsiveness, and remodeling. Histopathologically, patients with severe asthma have airway smooth muscle (ASM) hyperplasia and hypertrophy; subepithelial basement membrane thickening and fibrosis; all which contribute to fixed airflow limitation. Severe refractory asthma is very difficult to treat pharmacologically. It requires innovative therapies, such as bronchial thermoplasty which reduces the hypertrophied ASM mass and relieves the AHR, and broncoconstriction. Bronchial thermoplasty has been shown to improve asthma control, reduce severe exacerbations, hospitalizations, emergency room visits, and improve the quality of life, which persist up to 5 years following the procedure

scholarly journals Managing Severe Asthma: A Role for the Long-Acting Muscarinic Antagonist Tiotropium

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Eckard Hamelmann
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Gain Control ◽  
Clinical Trial Data ◽  
Cost Effective ◽  
Phase Iii ◽  
Muscarinic Antagonist ◽  
Phase Iii Clinical Trials ◽  
Cost Effective Treatment ◽  
Long Acting

Severe asthma is associated with substantial morbidity and mortality. Therapies must be maximized to gain control of a patient’s severe asthma; however, avoiding overtreatment is also important. The mainstays of asthma maintenance treatment are inhaled corticosteroids (ICS) and long-acting β2-agonsits (LABAs), with the option of supplementary add-on treatments. New add-on treatments for severe asthma have emerged over the past two decades, including personalized biological therapies that are guided by a patient’s asthma phenotype. In addition, the long-acting muscarinic antagonist tiotropium has been recommended as an add-on treatment for severe asthma. Phase III clinical trials have shown tiotropium in combination with ICS/LABA to be efficacious in patients with severe asthma. Further analyses of clinical trial data have indicated that there is no benefit in stratifying patients by phenotype to predict tiotropium efficacy. Furthermore, health economic studies suggest tiotropium to be a cost-effective treatment in patients with severe asthma. This review will present the evidence surrounding the role of tiotropium in severe asthma and will discuss the use of tiotropium add-on therapy before personalized medicine strategies in the stepwise process of gaining asthma control.

Asthma: Anti-Immunoglobulin E Therapy with Omalizumab for Asthma

2007 ◽  
Vol 41 (9) ◽  
pp. 1397-1410 ◽  
Author(s):  
Leslie Hendeles ◽  
Christine A Sorkness
Keyword(s):  
Clinical Trials ◽  
Cost Effectiveness ◽  
Randomized Clinical Trials ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
Data Extraction ◽  
Symptom Control ◽  
High Dose ◽  
Search Term ◽  
Ige Mediated

Objective: To evaluate data on anti-immunoglobulin E (anti-IgE) therapy for asthma. Data Sources: Information was selected from PubMed from 1989 to May 2007 using the search term omalizumab and included randomized, controlled trials. These studies evaluated asthma treatment with omalizumab and focused on its efficacy, tolerability, and cost-effectiveness in this population. Study Selection and Data Extraction: All randomized clinical trials were reviewed (23 were identified and 19 were included; 3 were not relevant and 1 contained duplicative data). Other articles using the search words anti-IgE therapy and cost-effectiveness were evaluated; relevant information was extracted. Data Synthesis: IgE-dependent mechanisms play an important role in the development and maintenance of airway inflammation in asthma. Omalizumab is a subcutaneously administered monoclonal anti-IgE antibody that reduces unbound IgE concentrations and promotes down-regulation of IgE receptors. Results from clinical trials in adults, adolescents, and children with poorly controlled IgE-mediated asthma have shown that omalizumab improves symptom control and allows patients to be managed with lower doses of inhaled corticosteroids (ICS). It has been well tolerated in clinical trials lasting as long as 52 weeks, but injection-site reactions are common (45% in omalizumab group vs 43% in placebo group) and anaphylaxis has occurred in 0.2% of patients. A consensus expert panel has recommended that omalizumab should be considered for patients 12 years of age or older with allergic asthma who are inadequately controlled on guideline-based therapy and require maintenance therapy with systemic corticosteroids or high-dose ICSs, or who have poor adherence to ICS therapy. Conclusions: Anti-IgE therapy provides an effective and generally safe approach to the treatment of patients with IgE-mediated asthma who are not adequately controlled by conventional guideline-based medications. However, the potential benefit must be weighed against the cost and inconvenience of this new therapy.

Triple therapy in uncontrolled asthma: a network meta-analysis of Phase III studies

2021 ◽  
pp. 2004233
Author(s):  
Paola Rogliani ◽  
Beatrice Ludovica Ritondo ◽  
Luigino Calzetta
Keyword(s):  
Meta Analysis ◽  
Phase Iii ◽  
Fixed Dose ◽  
High Dose ◽  
Severe Exacerbation ◽  
Triple Combination ◽  
Combination Therapies ◽  
Uncontrolled Asthma ◽  
Long Acting ◽  
The Impact

Conflicting evidence is currently available concerning the impact on asthma exacerbation of triple inhaled corticosteroid (ICS), long-acting β2-adrenoceptor agonist (LABA), and long-acting muscarinic receptor antagonist (LAMA) fixed-dose combination (FDC). Since meta-analyses allow settling controversies of apparently inconsistent results, we performed a network meta-analysis of Phase III randomised controlled trials including 9535 patients to assess the effect of ICS/LABA/LAMA combinations in uncontrolled asthma. Triple combination therapies with an ICS administered at high dose (HD) were more effective (p<0.05) than medium dose (MD) ICS/LABA/LAMA FDC and both MD and HD ICS/LABA FDCs against moderate to severe exacerbation (relative risk [RR] from 0.61 to 0.80) and increasing trough forced expiratory volume in the 1st second (mL from +33 to +114). Triple combination therapies including HD ICS were superior (p<0.05) than MD ICS/LABA/LAMA FDC in preventing severe exacerbation (RR from 0.46 to 0.65), but not with respect to moderate exacerbation (p>0.05). Triple combination therapies were equally effective on asthma control, with no safety concerns. This quantitative synthesis suggests that ICS/LABA/LAMA FDCs are effective and safe in uncontrolled asthma, and that the dose of ICS in the combination represents the discriminating factor to treat patients with a history of moderate or severe exacerbation.

scholarly journals First analysis of the Severe Paediatric Asthma Collaborative in Europe registry

2020 ◽  
Vol 6 (4) ◽  
pp. 00566-2020
Author(s):  
Norrice M. Liu ◽  
Karin C.L. Carlsen ◽  
Steve Cunningham ◽  
Grazia Fenu ◽  
Louise J. Fleming ◽  
...  
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Suboptimal Control ◽  
High Dose ◽  
Asthma Control Test ◽  
European Respiratory Society ◽  
Paediatric Asthma ◽  
Global Initiative For Asthma ◽  
Global Initiative ◽  
Long Acting

New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe.Data from 80 children with a clinical diagnosis of severe asthma who were receiving both high-dose inhaled corticosteroid and long-acting β2-agonist were entered into the registry between January 2019 and January 2020. Suboptimal control was defined by either asthma control test, or Global Initiative for Asthma criteria, or ≥2 severe exacerbations in the previous 12 months, or a combination.Overall, 62 out of 80 (77%) children had suboptimal asthma control, of whom 29 were not prescribed a biologic. However, in 24 there was an option for starting a licensed biologic. 33 children with suboptimal control were prescribed a biologic (omalizumab (n=24), or mepolizumab (n=7), or dupilumab (n=2)), and for 29 there was an option to switch to a different biologic.We conclude that the SPACE registry provides data that will support the planning of studies of asthma biologics. Not all children on biologics achieve good asthma control, and there is need for new trial designs addressing biologic switching.

Wirksamkeit und Sicherheit von Dupilumab bei ganzjähriger allergischer Rhinitis und gleichzeitigem Asthma

2019 ◽  
Vol 7 (1) ◽  
pp. 27-28
Author(s):  
Susanne Lau
Keyword(s):  
Allergic Rhinitis ◽  
Inhaled Corticosteroids ◽  
Persistent Asthma ◽  
High Dose ◽  
Specific Response ◽  
Pivotal Phase ◽  
Runny Nose ◽  
Asthma Patients ◽  
Long Acting ◽  
Snot 22

Background: Dupilumab, an anti-IL-4 receptor a mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting b2-agonists. Objective: To examine dupilumabʼs effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR). Methods: A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE >0.35 Ku/L). Results: Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, 25.98; 95% CI, 210.45 to 21.51; P 5.009) and all 4 AR-associated symptoms evaluated (nasal blockage, 20.60; 95% CI, 20.96 to 20.25; runny nose, 20.67; 95% CI, 21.04 to 20.31; sneezing, 20.55; 95% CI, 20.89 to 20.21; postnasal discharge, 20.49; 95% CI, 20.83 to 20.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (21.82; 95% CI, 26.46 to 2.83; P 5 .443 vs placebo) and in each ARassociated symptom. In patients without PAR, no differences were observed for these measures versus placebo. Conclusions: Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.

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