Treatment Of Severe Persistent Asthma Research Articles

Can anti-IgE and anti-IL-5 monoclonal antibodies be protective against household transmission of SARS-CoV-2?

Coronavirus disease 2019 (COVID-19) is the general term used for pneumonia caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Keeping the infected individuals in quarantine is very effective in preventing the spread of the disease but isolation and quarantine period increase the risk of household transmission. By December 2020, the rate of household transmission of SARS-CoV-2 has reached up to 85%. Both omalizumab and mepolizumab are used for the treatment of severe persistent asthma. In addition, omalizumab also has an indication for use in chronic urticaria. Both medications have been shown to have some antiviral effects. So, we aimed to discuss potential protective effects of these agents against household transmission of SARS-CoV-2 by reporting six different patients who remained uninfected despite PCR (Polymerase Chain Reaction) (+) SARS-CoV-2 individuals at home and were being treated with monoclonal antibodies.

Contributing Factors for Underutilization of Inhaled Corticosteroids Among Asthmatic Patients Attending at Adama Hospital Medical College, Adama, Ethiopia.

IntroductionInhaled corticosteroids (ICSs) are a cornerstone medicine for preventive therapy of persistent severe asthma. Although ICs are very effective for the treatment of severe persistent asthma, the majority of the prescribers worldwide aren’t aware of ICs use for the treatment of severe persistent asthma.ObjectiveTo evaluate factors contributing to underutilization of ICS by asthmatic patients.MethodsPatient interview was conducted among asthmatic patients using a cross-sectional study design who were attending at the Adama Hospital Medical College from March 1 to July 25, 2017. The total number of patients involved in the study was 94. Semi-structured questionnaire through patient interview was used for data collection and data from physicians who were working at the chest clinic of AHMC were collected by self-administered semi-structured questionnaire focusing their perspectives and experiences on patients’ ICS.ResultsGenerally 73.5% of underutilization of ICS was reported from the total number of patients involved in the study according to the patient’s perception. Monthly income, comorbid disease, and behaviors of ICS use were the main factors contributing to underutilization of ICS. According to patient’s report, some of the reasons for underutilization of ICS were unaffordability, using the drugs only when symptoms appear, inaccessibility, side effects and recommendation by physicians. There were also similar reports by the physicians working in the AHMC.ConclusionIn our study setting, prevalence of underutilization of ICS was high and the contributing factors were increased cost of ICS, inaccessibility of ICS, poor knowledge of the patients on asthma disease and ICS, bad attitude toward ICS, and lack of recently reviewed local guideline for asthma treatment. Thus, concerned experts need to take actions that guarantee accessibility of ICS at a reasonable price and increase awareness of patients about asthma disease and use of ICS.

Treatment of severe persistent asthma with IL-6 receptor blockade

Treatment of severe persistent asthma with IL-6 receptor blockade

Bronchial Thermoplasty: A Decade of Experience: State of the Art

Bronchial thermoplasty (BT) delivers targeted radiofrequency energy to bronchial airway walls and results in the partial ablation of the airway smooth muscle that is responsible for bronchoconstriction. It is approved for the treatment of severe persistent asthma. Multiple, large clinical trials including a recent "real-world" study demonstrate significant improvements in asthma-related quality of life, reduction in asthma exacerbations, emergency department visits, and hospitalizations after BT that is sustained out to 5 years. In this article, we review the state of the art of BT treatment in severe persistent asthma and share a decade of BT research and clinical experience. We share our personal experience and introduce the three "I"s (identification, implementation, and intense follow-up) that we believe promote successful patient outcomes and help build a successful BT program.

Cost-Effectiveness Analysis of Omalizumab for the Treatment of Severe Persistent Asthma in Real Clinical Practice in Spain.

Omalizumab is a humanized monoclonal antibody that targets circulating immunoglobulin E molecules to treat severe uncontrolled asthma. The aim of this study was to determine the cost effectiveness of omalizumab compared with standard treatment for the control of severe persistent asthma according to data from patients treated in a specialized asthma unit. This was an observational, retrospective, single-center study in the setting of the Pulmonology and Respiratory Allergy Service, Thorax Institute, Hospital Clínic de Barcelona, Barcelona, Spain. Data were collected by review of medical records of 86 uncontrolled severe persistent asthma patients treated with omalizumab from January 2005 to April 2014. Effectiveness was assessed by the reduction in asthma exacerbations and 3-point increases in the Asthma Control Test (ACT) score. The economic evaluation was performed from the societal perspective, including direct health costs (resource use and drug treatments) and indirect costs (disease impact on labor productivity) in 2016 Euros. The time horizon was 12months before and after the initiation of treatment with omalizumab. Results were expressed using the incremental cost-effectiveness ratio (ICER). Taking into account only direct costs, the ICERs were €1487.46 (95% confidence interval [CI] 1241.21-1778.34) per exacerbation avoided and €5425.13 (95% CI 4539.30-6551.03) per 3-point increase in the ACT. When indirect costs were included, the ICERs were €1130.93 (95% CI 909.08-1392.86) per exacerbation avoided, and €4124.79 (95% CI 3281.69-5186.73) per 3-point increase in the ACT. The results of this study confirm the effectiveness of the addition of omalizumab to standard therapy in patients with uncontrolled severe persistent asthma.

Efficacy and Safety of Tiotropium in the Treatment of Severe Persistent Asthma:Meta-analysis.

To evaluate the efficacy and safety of tiotropium in treatment of severe persistent asthma. Reports of randomized controlled trials (RCTs) describing tiotropium for treatment of severe persistent asthma published from January 1946 to February 2015 were searched in Cochrane Library, ClinicalTrials.gov, PubMed, Ovid Medline, CNKI, and CSJD. The data of the included RCTs were extracted and the data quality was evaluated. Meta-analyses were performed with Revman 5.3 software. Five RCTs including 1433 patients were analyzed. Meta-analysis of the data showed that compared with the placebo group, tiotropium treatment significantly improved the patients' peak forced expiratory volume in one second (FEV1) [weighted mean difference (WMD): 0.13 L, 95% confidence interval (CI): 0.10-0.16 L, P<0.00001], trough FEV1 (WMD: 0.09 L, 95%CI: 0.06-0.12 L, P<0.00001), peak forced vital capacity (FVC) (WMD: 0.10 L, 95%CI: 0.06-0.14 L, P<0.00001), trough FVC (WMD: 0.12 L, 95%CI: 0.08-0.17 L, P<0.00001), morning peak expiratory flow (PEF) (WMD: 9.21 L/min, 95%CI: 4.2-14.23 L/min, P=0.0003), evening PEF (WMD: 22.06 L/min, 95%CI 13.05-31.08 L/min, P<0.00001). The scores of asthma control questionnaire (ACQ) (WMD: 0.01, 95% CI: -0.07-0.09, P=0.86) or asthma quality of life questionnaire (AQLQ)(WMD: 0.06, 95% CI:-0.18-0.06, P=0.33) were not affected by tiotropium. No significant difference with adverse events between tiotropium group and placebo group were reported in these included studies (P>0.05). Tiotropium for severe persistent asthma treatment can improve FEV1, FVC, and PEF but may not improve the quality of life of the patients. Tiotropium is well tolerated and can be an add-on therapy for severe persistent asthma.

Cost effectiveness of bronchial thermoplasty in patients with severe uncontrolled asthma

Rationale: Based on its clinical effectiveness, bronchial thermoplasty (BT) was approved by the Food and Drug Administration in 2010 for the treatment of severe persistent asthma in patients 18 years and older whose asthma is not well-controlled with inhaled corticosteroids and long-acting beta-agonist medicines. Objective: Assess the 10 year cost-effectiveness of BT for individuals with severe uncontrolled asthma. Methods: Using a Markov decision analytic model, the cost-effectiveness of BT was estimated. The patient population involved a hypothetical cohort of 41-year-old patients comparing BT to usual care over a 10-year time frame. The main outcome measure was cost in 2013 dollars per additional quality adjusted life year (QALY). Results: Treatment with BT resulted in 6.40 QALYs and $7512 in cost compared to 6.21 QALYs and $2054 for usual care. The incremental cost-effectiveness ratio for BT at 10 years was $29 821/QALY. At a willingness to pay per QALY of $50 000, BT continues to be cost effective unless the probability of severe asthma exacerbation drops below 0.63 exacerbation per year or the cost of BT rises above $10 384 total for all three bronchoscopic procedures needed to perform thermoplasty and to cover the entire bronchial tree (baseline = $6690). Conclusions: BT is a cost-effective treatment for asthmatics at high risk of exacerbations. Continuing to follow asthmatics treated with BT beyond 5 years will help inform longer efficacy and support its cost-effectiveness.

Salmeterol Xinafoate.

Salmeterol xinafoate is a potent and a long-acting β2-adrenoceptor agonist. It is prescribed for the treatment of severe persistent asthma and chronic obstructive pulmonary disease. Different methods were used to prepare (R)-(-)-salmeterol such as: mixing a sample of 4-benzyloxy-3-hydroxymethyl-ω-bromoacetophenone with sodium lauryl sulfate and the mixture was added to the microbial culture of Rhodotorula rubra, treatment of p-hydroxyacetophenone with Eschenmoser's salt and carbonate exchange resin followed by a sequence of supported reagents and scavenging agents or via Rh-catalyzed asymmetric transfer hydrogenation. The enantioselective synthesis of (S)-salmeterol was achieved via asymmetric reduction of the azidoketone 4 by Pichia angusta yeast. Physical characteristics of salmeterol xinafoate were confirmed via: X-ray powder diffraction pattern, thermal analysis and UV, vibrational, nuclear magnetic resonance, and mass spectroscopical data. Initial improvement in asthma control may occur within 30 min following oral inhalation of salmeterol in fixed combination with fluticasone propionate. Clinically important improvements are maintained for up to 12 h in most patients. It is extensively metabolized in the liver by hydroxylation, thus increased plasma concentrations may occur in patients with hepatic impairment.

PRS41 - Integrating the Long-Term Health Burden of Oral Corticosteroids in the Cost-Effectiveness of Omalizumab

Omalizumab offers an alternative to maintenance oral corticosteroids (OCS) in the treatment of severe persistent asthma. Despite widespread recognition of the adverse effects from OCS, there is little quantitative evidence on their health burden or costs. Failing to account for the adverse effects of OCS may underestimate the cost-effectiveness of innovative steroid-sparing medicines such as omalizumab. This study aims to explore the possibilities for integrating evidence on the burden of OCS in cost-effectiveness analysis using omalizumab as a case study. A model was developed to evaluate the long-term cost-effectiveness of omalizumab in patients requiring maintenance OCS. Costs were from a health service perspective and outcomes were measured as quality-adjusted life years (QALYs). The burden from maintenance use of OCS was quantified with population-based approach, with a decision model and with threshold analysis. The incremental cost-effectiveness ratio (ICER) was £37,987 per QALY gained, which is above conventional thresholds used in the UK. Threshold analysis showed that the annual health losses from maintenance use of oral corticosteroids would need to be 0.12 QALYs per year. This is double the quantifiable health losses with the population-based approach and with the decision model and 10% of the health gains achieved with omalizumab. The burden from maintenance OCS can be integrated in cost-effectiveness analysis but the extent to which these estimates account for their full impact on health depends on the approach used and underlying assumptions. The challenges arise from sparse randomised evidence, time lag in the adverse effects and unclear relationship between risk and long-term steroid load. These are empirical questions which can be answered with further research. Such research would be valuable not only for decision making in severe asthma but also for other conditions treated with maintenance OCS.

Bronchial Thermoplasty: Therapeutic Success in Severe Asthma Associated with Persistent Airflow Obstruction

Introduction. Severe persistent asthma is a disabling condition associated with significant morbidity and rising mortality worldwide. The recent advent of bronchial thermoplasty (BT) has offered a revolutionary therapeutic option for the treatment of severe persistent asthma. This minimally invasive bronchoscopic procedure focuses on anatomical manipulation of bronchial smooth muscle to attenuate airway hyperresponsiveness. Case report. This case report describes treatment of a 42-year-old female with BT for her debilitating asthma. Following a complicated treatment course of BT, she attained significant relief from her symptoms and had noticeably improved functionality. Conclusion. This case represents BT success and a change to the traditional paradigm governing the treatment of refractory asthma.

Omalizumab for the treatment of severe persistent allergic asthma in children aged 6–11 years

This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of omalizumab for the treatment of severe persistent asthma in children aged 6-11 years, based upon the evidence submission from Novartis Pharmaceutical UK Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The manufacturer's submission was generally considered to be of good quality. The submission was based primarily on a preplanned subgroup IA-05 EUP (European Union Population) from the IA-05 trial, with outcomes including the number of clinically significant (CS) and clinically significant severe (CSS) exacerbations. Omalizumab therapy was associated with a statistically significant reduction in the rate of CS exacerbations, but the reduction in the rate of CSS exacerbations was not statistically significant. The benefit in terms of CS exacerbations was achieved mainly in patients with more than three exacerbations per year at baseline. The manufacturer found no previous published cost-effectiveness studies of omalizumab in children aged 6-11 years, so their de novo economic evaluation formed the basis of the submitted economic evidence. The economic model was considered appropriate for the decision problem. The results from the model indicated that omalizumab in addition to standard therapy compared with standard therapy alone did not appear cost-effective in either the overall population or a subgroup of patients hospitalised in the year prior to enrollment, with incremental cost-effectiveness ratios of £ 91,169 and £ 65,911 per quality-adjusted life-year, respectively. These findings were found to be robust across a wide range of alternative assumptions through one-way sensitivity analyses. The guidance issued by NICE states that omalizumab is not recommended for the treatment of severe persistent allergic asthma in children aged 6-11 years.

Omalizumab for the treatment of severe persistent allergic asthma in children aged 6–11 years

This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of omalizumab for the treatment of severe persistent asthma in children aged 6–11 years, based upon the evidence submission from Novartis Pharmaceutical UK Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The manufacturer’s submission was generally considered to be of good quality. The submission was based primarily on a preplanned subgroup IA-05 EUP (European Union Population) from the IA-05 trial, with outcomes including the number of clinically significant (CS) and clinically significant severe (CSS) exacerbations. Omalizumab therapy was associated with a statistically significant reduction in the rate of CS exacerbations, but the reduction in the rate of CSS exacerbations was not statistically significant. The benefit in terms of CS exacerbations was achieved mainly in patients with more than three exacerbations per year at baseline. The manufacturer found no previous published cost-effectiveness studies of omalizumab in children aged 6–11 years, so their de novo economic evaluation formed the basis of the submitted economic evidence. The economic model was considered appropriate for the decision problem. The results from the model indicated that omalizumab in addition to standard therapy compared with standard therapy alone did not appear cost-effective in either the overall population or a subgroup of patients hospitalised in the year prior to enrolment, with incremental cost-effectiveness ratios of £91,169 and £65,911 per quality-adjusted life-year, respectively. These findings were found to be robust across a wide range of alternative assumptions through one-way sensitivity analyses. The guidance issued by NICE states that omalizumab is not recommended for the treatment of severe persistent allergic asthma in children aged 6–11 years.

Persistence of effectiveness of bronchial thermoplasty in patients with severe asthma

Bronchial thermoplasty (BT) has been demonstrated to be safe and effective in the treatment of severe persistent asthma out to at least 1 year. Preclinical studies have demonstrated that the reduction in airway smooth muscle after bronchial thermoplasty persists out to at least 3 years. To examine the persistence of effectiveness of BT 2 years posttreatment in subjects with severe asthma. Subjects participating in the long-term safety follow-up phase of the Asthma Intervention Research 2 (AIR2) Trial were evaluated by comparing the proportion of subjects who experienced exacerbations, adverse events, or healthcare utilization during the first year (year 1) after BT treatment with the proportion of subjects who experienced the same during the subsequent 12 months (year 2). Severe exacerbations, respiratory adverse events, emergency department visits for respiratory symptoms, and hospitalizations for respiratory symptoms (proportion of subjects experiencing and rates of events), and stability of pre- and post-bronchodilator forced expiratory volume in 1 second (FEV(1)), were comparable between years 1 and 2. The proportion of subjects experiencing severe exacerbations in year 2 after BT was 23.0%, compared with 30.9% in year 1. The reduction in the proportion of subjects experiencing severe exacerbations after BT is maintained for at least 2 years. Bronchial thermoplasty provides beneficial long-term effects on asthma outcomes in patients with severe asthma. clinicaltrials.gov, Identifier: NCT00231114.

Anti-IgE bei respiratorischen Erkrankungen: Klinische Evidenz zu Wirksamkeit und Sicherheit bei allergischem Asthma

Anti-IgE (omalizumab) reduces the allergic airway inflammation by binding of circulating, free immunoglobulin E. This leads to a significant improvement of allergic asthma. Seven Phase III studies in juveniles and adults demonstrate that omalizumab offers an effective and safe, new therapeutic option in the treatment of severe persistent asthma, not sufficiently controlled by standard therapy according to recent guidelines. It appears that even with regard to cost-effectiveness omalizumab could be a valuable new therapeutic option in severe persistent asthma, providing a significant reduction of asthma symptoms, asthma medication, rate of asthma exacerbations and emergency treatment, and improvement of asthma-related quality of life. Severe adverse effects are very rare.

Comparison of the efficacy and safety of nebulized beclometasone dipropionate and budesonide in severe persistent childhood asthma

Inhaled steroids are recommended for long-term control of asthma, but their use may be limited in young children because of difficulties in using the associated inhaler device. The use of nebulizers may help to overcome this issue, without compromising therapeutic efficacy or safety. This 14-week, multicentre, randomized, controlled, open-label, parallel-group study compared the efficacy and safety of nebulized corticosteroids in paediatric patients (aged 6 months to 6 years) with severe persistent asthma. Beclometasone dipropionate (BDP) 800 μg day −1 suspension for nebulization and budesonide (BUD) 750 μg day −1 given by nebulization in a twice-daily regimen, and when used in addition to the usual maintenance therapy, resulted in comparable clinical efficacy across all parameters. The primary efficacy endpoint was the number of patients who did not experience any major exacerbation, this being 40·4% and 51·7% in the BDP and BUD groups respectively in the ITT population ( P=0·28), and the mean number of global exacerbations (major plus minor) decreased respectively by −37.5% in the BDP group and −23.3% in the BUD group. Both treatments were also associated with marked reductions in the number of nights with wheezing and the number of days of oral steroid use. Moreover, the two treatment groups had a similar adverse-event incidence and profile. Only 11 adverse events were reported, and no serious adverse events were related to treatment. Urinary cortisol and the time course of height and weight were unaffected by both treatments, and BDP was confirmed to have a neutral effect on bone metabolism. In conclusion, this study demonstrates that both BDP 800 μg day −1 suspension for nebulization and BUD 750 μg day −1 administered by nebulization are effective, with an acceptable safety profile, for treatment of severe persistent asthma in infants and young children.