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.

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.

Economic evaluation of 5-HT3 receptor antagonists in combination with dexamethasone for the prevention of ‘overall’ nausea and vomiting following highly emetogenic chemotherapy in Chinese adult patients

2016 ◽  
Vol 23 (6) ◽  
pp. 403-412 ◽  
Author(s):  
Qiong Du ◽  
Qing Zhai ◽  
Bin Zhu ◽  
Xiao-Le Xu ◽  
Bo Yu
Keyword(s):  
Economic Evaluation ◽  
Cost Effective ◽  
Emetogenic Chemotherapy ◽  
Adult Patients ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Highly Emetogenic Chemotherapy ◽  
Chinese Adult ◽  
Cost Effective Treatment ◽  
The Impact

Background Two pivotal Phase III trials compared the efficacy of palonosetron, ondansetron and granisetron, combined with dexamethasone, for the prevention of nausea and vomiting following highly emetogenic chemotherapy. However, an economic evaluation of these three regimens in the real-world setting of Chinese adult patients has not been determined. Objectives To estimate, from the perspective of the Chinese healthcare system, which of these frequently used strategies consisting of 0.25 mg palonosetron (0.25P), 16 mg ondansetron (Onda), and 3 mg granisetron (Gran), is the most cost-effective option in patients following highly emetogenic chemotherapy. Methods A Markov decision-analytic model was developed. The health and economic outcomes of the three strategies; 0.25P, Onda, and Gran were investigated. The clinical and utility data were taken from published studies. The cost data were calculated according to current local Chinese practices. Sensitivity analyses were performed to determine the impact of uncertainty regarding the results. Results The base-case analysis showed that the 0.25P strategy yielded maximum health benefits compared with the other two strategies. However, the probabilistic sensitivity analysis demonstrated that the Gran strategy was the most cost-effective approach when the willingness-to-pay threshold was not more than US$22,515/quality-adjusted life year. Moreover, palonosetron is not cost-effective in preventing ‘overall’ nausea and vomiting following highly emetogenic chemotherapy in Chinese patients. Conclusions Our analysis suggests that, compared with palonosetron and ondansetron, 3 mg granisetron may be a cost-effective treatment option in the current Chinese healthcare setting.

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 The Role of Nicotinamide in Cancer Chemoprevention and Therapy

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 477 ◽  
Author(s):  
Ilias P. Nikas ◽  
Stavroula A. Paschou ◽  
Han Suk Ryu
Keyword(s):  
Clinical Trials ◽  
Cancer Chemoprevention ◽  
Cost Effective ◽  
Water Soluble ◽  
Sirtuin 1 ◽  
Phase Iii ◽  
Soluble Form ◽  
Vitamin B3 ◽  
Preclinical Research ◽  
Phase Iii Clinical Trials

Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value.

scholarly journals Evaluation of the pharmacoeconomics of drugs used for the treatment of long-term complications of sulfur mustard

2016 ◽  
Vol 10 ◽  
Author(s):  
Yunes Panahi ◽  
Mostafa Ghanei ◽  
Milad Vakili Zarch ◽  
Zohreh Poursaleh ◽  
Shahram Parvin ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Inhaled Corticosteroids ◽  
Sulfur Mustard ◽  
Cost Effective ◽  
Chemical Warfare Agent ◽  
Pulmonary Complications ◽  
High Dose ◽  
Chemical Injuries ◽  
Long Acting

Sulfur mustard (SM), a cytotoxic vesicant chemical warfare agent, has powerful irritant and blistering effects on the skin, eyes and respiratory tract. Since during the Iraq-Iran war, many Iranian soldiers and civilians were exposed to SM, there are several victims still suffering from long-term cutaneous, ocular and pulmonary complications. Currently, there is no definite treatment for long-term complications of SM, and only supportive medical care is being taken to minimize the symptoms. In this study, we compared the cost-effectiveness of common drugs that are used against long-term SM-induced complications in Iranian patients. In this review article, electronic databases were checked using the following key words: sulfur mustard, lung, skin, eye, cost-effectiveness, pharmacoeconomics and treatment. Abstracts of non-English papers and proceedings of congresses on SM were also assessed. Among the studied drugs, high-dose oral N-acetyl cysteine and long-acting inhaled corticosteroids against respiratory complications, topical corticosteroids and oral antihistamines against cutaneous complications and NSAIDS and corticosteroids ophthalmic drops against ocular complications were found to be cost-effective. Usage of different drugs in the treatment of SM injuries in Iran, have imposed a significant economic burden to patients and their families because many drugs that are effective against chemical injuries are not covered by insurance. In addition, development of more effective drugs in this field is considered as an urgent demand that should be noticed by the pharmaceutical industry.

scholarly journals Global Initiative for Asthma (GINA) Strategy 2021 - Executive summary and rationale for key changes

2021 ◽  
pp. 2102730
Author(s):  
Helen K. Reddel ◽  
Leonard B. Bacharier ◽  
Eric D. Bateman ◽  
Christopher E. Brightling ◽  
Guy G. Brusselle ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Age Groups ◽  
Skills Training ◽  
Mild Asthma ◽  
Executive Summary ◽  
Global Initiative For Asthma ◽  
Global Initiative ◽  
Long Acting ◽  
Beta2 Agonist

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes.GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting beta2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as- needed combination ICS-formoterol reduces severe exacerbations by >60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function and inflammatory outcomes as daily ICS plus as-needed SABA.Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as-needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, MART) in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting beta2-agonist (LABA) (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11  years, new treatment options are added at Steps 3-4.Across all age-groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment and review remain essential to optimize asthma outcomes.

scholarly journals Algorithm of biophenotyping and choice of medication for targeted therapy of severe uncontrolled asthma with eosinophilic type of airways inflammation

2017 ◽  
Vol 14 (3) ◽  
pp. 5-18
Author(s):  
N I Ilina ◽  
N M Nenasheva ◽  
S N Avdeev ◽  
Z R Aisanov ◽  
V V Arkhipov ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Clinical Studies ◽  
Inhaled Corticosteroids ◽  
Uncontrolled Asthma ◽  
Treatment Regimens ◽  
Expert Opinions ◽  
Beta Agonists ◽  
Biomarker Testing ◽  
High Doses ◽  
Long Acting

The article is based on the resolution of the Expert Council, including experts from Russian Association of Allergists and Clinical Immunologists (RAACI) and Russian Respiratory Society (RRS) dated November 20, 2016, and the review of clinical studies results and publications on the biomarker-based diagnosis and biological treatment of severe uncontrolled asthma. The aim of this work is to develop a phenotype-oriented algorithm of diagnostics and treatment of severe asthma, supported by the biomarker testing for subsequent selection of appropriate immunobiological treatment. The article constitutes the summary of results of clinical studies and expert opinions on the treatment of asthma in patients who do not achieve disease control with standard treatment regimens including high doses of inhaled corticosteroids in the combination with long-acting beta-agonists, tiotropium, and medications from other pharmacological groups according to Russian Respiratory Society (2016) and GINA (2016-2017) guidelines. The article summarizes the results of international randomized clinical studies performed to assess safety and efficacy of new class of biological treatments, monoclonal antibodies acting against major cytokines that are responsible for inflammation, in patients with severe asthma, including a new anti-IL-5 antibody, reslizumab (Cinqaero).

scholarly journals Pro: Inhaled corticosteroids for chronic obstructive pulmonary disease

2019 ◽  
Vol 2 (1) ◽  
pp. 35-40
Author(s):  
Donald A. Mahler
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Mechanisms Of Action ◽  
Phase Iii ◽  
Chronic Obstructive ◽  
Exacerbation Rate ◽  
Obstructive Pulmonary Disease ◽  
Long Acting

Background: Controversy exists about the use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD). Although ICS are not approved as monotherapy for COPD, four ICS molecules, beclomethasone, budesonide, fluticasone furoate, and fluticasone propionate, are used widely in combination with long-acting bronchodilators to treat patients with this disease. Objectives: (1) To review the mechanisms of action of ICS therapy that contribute to the clinical benefits in COPD; and (2) to describe improvements in lung function, relief of dyspnea, increase in exercise tolerance, and the reduction in exacerbations with ICS use in COPD. Methods: A critical review of phase III and IV randomized clinical trials that evaluated ICS therapy in patients with COPD. Results: ICS have two major mechanisms of action in human airways: a reduction in edema and inflammation, and a decrease in airway hyperresponsiveness. ICS monotherapy significantly increases the morning peak expiratory flow rate and forced expiratory volume in 1 second (peak and trough) as early as the first day of treatment. Discontinuation of ICS therapy leads to deterioration in lung function. Treatment with ICS, alone and in combination with a long-acting bronchodilator, reduces dyspnea related to daily activities, whereas withdrawal increases breathing difficulty. Patients with COPD exhibit a significant increase in exercise duration with ICS therapy. The combination of ICS with one or more bronchodilators significantly reduces the exacerbation rate compared with bronchodilator therapy alone. The major serious adverse effect is an increased risk of pneumonia. Conclusion: Randomized controlled trials demonstrate that ICS therapy improves both physiologic and clinical outcomes in patients with COPD. These benefits are enhanced when ICS molecules are combined with one or more long-acting bronchodilators.

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