Severe asthma is a subtype of asthma that is difficult to treat and control. By conservative estimates, severe asthma affects approximately 5–10% of patients with asthma worldwide. Severe asthma impairs patients' health-related quality of life, and patients are at risk of life-threatening asthma attacks. Severe asthma also accounts for the majority of health care expenditures associated with asthma. Guidelines recommend that patients with severe asthma be referred to a specialist respiratory team for correct diagnosis and expert management. This is particularly important to ensure that they have access to newly available biologic treatments. However, many patients with severe asthma can suffer multiple asthma attacks and wait several years before they are referred for specialist care. As global patient advocates, we believe it is essential to raise awareness and understanding for patients, caregivers, health care professionals, and the public about the substantial impact of severe asthma and to create opportunities for improving patient care. Patients should be empowered to live a life free of symptoms and the adverse effects of traditional medications (e.g., oral corticosteroids), reducing hospital visits and emergency care, the loss of school and work days, and the constraints placed on their daily lives. Here we provide a Patient Charter for severe asthma, consisting of six core principles, to mobilize national governments, health care providers, payer policymakers, lung health industry partners, and patients/caregivers to address the unmet need and burden in severe asthma and ultimately work together to deliver meaningful improvements in care.
Publisher's version (útgefin grein) ; Background: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour. Methods: ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC; comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (=18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR's collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics and Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders. Conclusions: ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally. ; The International Severe Asthma Registry is conducted by Optimum Patient Care Global Limited, and co-funded by Optimum Patient Care Global Limited and AstraZeneca. ISAR is supported by grants from AstraZeneca and Optimum Patient Care (OPC) Global (a not-for-profit social enterprise). The ISAR steering committee (ISC) was involved in the development of the protocol and is responsible for approving research proposals via a democratic voting process. In addition to 47 clinicians and researchers with an interest and experience in severe asthma, the ISC also includes members of OPC and four medical experts from AstraZeneca. AstraZeneca reviewed the draft before submission; however, decision to submit was made by the authors. Medical writing support was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). ; Peer Reviewed
Bronchial thermoplasty is an intervention developed for the treatment of asthma through the delivery of radio frequency energy to the airways [1, 2]. Evidence for the efficacy and safety of bronchial thermoplasty in severe asthma is based on the results of three randomised controlled trials [3–5]. Two trials compared bronchial thermoplasty with usual care, the Asthma Intervention Research (AIR) trial [3] and the Research in Severe Asthma (RISA) trial [4], whereas the third trial (AIR2) compared bronchial thermoplasty with a sham procedure [5]. The AIR2 trial reported improved asthma quality of life questionnaire (AQLQ) scores, reduced severe exacerbations and decreased emergency department visits in the post-bronchial thermoplasty treatment period [5]. Bronchial thermoplasty was associated with a short-term increase in asthma-related symptoms and hospital admissions for asthma during the treatment phase [3–5]. Follow-up observational studies to date support the long-term safety of the procedure, based on unchanged rates of respiratory adverse events, lung function, serial computed tomography scans and rates of hospital admissions or emergency department visits in years 2–5 following the AIR [6], RISA [7] and AIR2 trials [8]. A Cochrane systematic review of the trials concluded that there was a modest clinical benefit in asthma quality of life and a reduction in exacerbation rates 12 months after bronchial thermoplasty [9]. In 2010, the Food and Drug Administration (FDA) gave premarket approval for the Alair bronchial thermoplasty system (Boston Scientific, Marlborough, MA, USA) as a treatment for severe persistent asthma in patients 18 years and older whose asthma is not well controlled with inhaled corticosteroids and a long-acting β-agonist [10]. Bronchial thermoplasty is also approved for the treatment of asthma in the European Union and in many countries worldwide.
Pierluigi Paggiaro,1 Simona Barbaglia,2 Stefano Centanni,3,4 Davide Croce,5 Enrico Desideri,6 Saffi Giustini,7,8 Claudio Micheletto,9 Antonino Musarra,10 Nicola Scichilone,11 Ugo Trama,12 Maria Teresa Zedda,7,13 Giorgio Walter Canonica14 1Department of Surgery, Medicine, Molecular Biology, and Critical Care, University of Pisa, Pisa, Italy; 2Associazione Nazionale Pazienti "Respiriamo Insieme", Padova, Italy; 3Department of Health Sciences, Università degli Studi di Milano, Milan, Italy; 4Respiratory Unit, ASST Santi Paolo e Carlo, Milan, Italy; 5Center for Health Economics, Social and Health Care Management, LIUC-Università Cattaneo, Castellanza, Italy; 6Fondazione Innovazione e Sicurezza in Sanità, Rome, Italy; 7Italian General Practitioners' Association "SIMG", Florence, Italy; 8Local Health Unit of Montale, Pistoia, Italy; 9Cardio-Thoracic Department, Respiratory Unit, Integrated University Hospital, Verona, Italy; 10Allergy Unit, National Healthcare System, Reggio Calabria, Italy; 11Biomedical Department of Internal and Specialist Medicine, University of Palermo, Palermo, Italy; 12Dirigente UOD 06 Politica del Farmaco e Dispositivi, Naples, Italy; 13General Practice, Cagliari, Italy; 14Personalized Medicine Asthma & Allergy Clinic, Humanitas University and Research Hospital-IRCCS, Milan, ItalyCorrespondence: Pierluigi PaggiaroDepartment of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Via Paradisa No. 2, Pisa, 56124, ItalyTel +39 050 995365Fax +39 050 580124Email pierluigi.paggiaro@unipi.itIntroduction: People with severe asthma (SA) often have poor disease control and quality of life, and are at high risk of exacerbations, lung function decline and asthma-related death. The present expert opinion article aimed to identify unmet needs in the management of SA in Italy, and propose possible solutions to address these needs.Methods: At five multidisciplinary events in Italy, attendees identified factors that interfered with the effective management of SA and suggested how these barriers could be overcome. A core group of 12 Italian experts (pulmonologists, general practitioners, allergists, payers and patients) identified the main issues and proposed possible solutions based on the results from the meetings and relevant articles from the literature.Results and Conclusions: We reviewed the gap between real-world practice and guidelines, oral corticosteroid overuse, SA-related mortality, and barriers to effective SA treatment. Common themes were lack of awareness about SA among both patients and clinicians, and lack of networking/information exchange between those involved in the treatment of SA. Participants agreed on the need to implement patient education and create multidisciplinary groups of specialists to improve SA management through multidisciplinary educational initiatives, meetings with local experts, development of a flow chart for referral/connection with local experts and specialized centers. Clinical instruments that might help specialists improve SA management included referral networks, integrated care pathways, phenotyping and treatment algorithms, exacerbation tracking, and examination of electronic medical records for patients with uncontrolled asthma. The following actions need to be implemented in Italy: i) maximize the use of advanced therapies, eg, biologics; ii) increase/improve education for physicians and patients; iii) improve multidisciplinary communication and care coordination; iv) introduce regional and local protocols for SA diagnosis and treatment; and v) change the structure of healthcare services to reduce specialist waiting times and facilitate access to biologic therapies.Keywords: biologic therapy, expert opinion, oral corticosteroids, severe asthma, unmet needs
Acknowledgements The authors thank the following individuals who contributed to the initial set-up of ISAR, provided input to the development of the protocol and/or were involved in local implementation of ISAR: Elisabeth Bel, Roland Buhl, Sverre Lehmann, Stelios Loukidis, Richard Martin, Juno Pak, Pearlanne Zelar ney, Joy Zimmer, Christena Kolakowski, Margo Brown, Jessica Cummings, Jennifer Brandorff, Seth Skelton, John Upham, Philip Bardin, Paul Reynolds, David Langton, Peter Middleton, Belinda Cochrane, Katya Vasileva Noleva, Plamen Hristov Yakovliev, Sonya Metodieva Genova, Violina Milchova Vasi leva, Darina Petrova Dimova, Nadezhda K Takovska, Cvetantka Hristova Odz hakova, Eleonora M Stamenova, Diana X Hristova, Vincente Plaza, Ian Hirsch, Cekomir Vodenicharov, Alexandrina Vodenicharova and Magdalena Alexandrova. Medical writing support was provided by Michelle Rebello, PhD, and Liam Gillies, PhD, of Cactus Communications (Mumbai, India). Funding The International Severe Asthma Registry is conducted by Optimum Patient Care Global Limited, and co-funded by Optimum Patient Care Global Limited and AstraZeneca. ISAR is supported by grants from AstraZeneca and Optimum Patient Care (OPC) Global (a not-for-profit social enterprise). The ISAR steering committee (ISC) was involved in the development of the protocol and is responsible for approving research proposals via a democratic voting process. In addition to 47 clinicians and researchers with an interest and experience in severe asthma, the ISC also includes members of OPC and four medical experts from AstraZeneca. AstraZeneca reviewed the draft before submission; however, decision to submit was made by the authors. Medical writing support was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). ; Peer reviewed ; Publisher PDF
U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p
AbstractIndoor air pollution is increasingly recognized as a significant risk for respiratory illness, particularly in vulnerable populations. Thirty-six children aged 6–14 years with moderate/severe asthma from inner city areas in New York City were studied for 2-week periods (summer and winter) using diaries and spirometry. Seven-day integrated indoor samples of PM10, PM2.5, trace elements, elemental/organic carbon, black carbon, and criteria gases (NO2, SO2, and O3) were collected in the subjects' residences. Asthma outcomes included cough and wheeze severity, albuterol use, and pulmonary function. Mixed effects regression models for longitudinal data were used to relate weekly indoor pollutant concentrations to asthma outcomes. Odds ratios (ORs) were calculated for ordinal outcomes. During winter, significant positive associations for average weekly symptom severity scores were seen for NO2(OR = 2.83;p = 0.02), calcium (OR = 3.29;p = 0.02), and silicon (OR = 3.64;p = 0.04). In summer, chlorine was associated with average weekly symptom scores (OR = 1.85;p = 0.004). Average albuterol puff use per day in winter was associated with NO2(OR = 5.89;p = 0.009), nickel (OR = 2.27;p = 0.05), and silicon (OR = 5.59;p = 0.05). Albuterol use was not associated with indoor pollutants in summer. Asthma severity was associated with specific indoor pollutants. Seasonal differences were observed by pollutant and by clinical index studied.
Søren E Pedersen,1 Niyati Prasad,2 Udo-Michael Goehring,3 Henrik Andersson,4 Dirkje S Postma5 1Pediatric Research Unit, Kolding Hospital, University of Southern Denmark, Kolding, Denmark; 2Vertex, Phase IV & Global Strategy, London, UK; 3Vifor Pharma Ltd, Clinical Research & Biometrics, Glattbrugg, Switzerland; 4Swedish Social Insurance Agency, Government Offices of Sweden, Stockholm, Sweden; 5Department of Pulmonology, Griac Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Background: The inhaled corticosteroid (ICS) ciclesonide (Cic), controls asthma symptoms in the majority of patients at the recommended dose of 160 µg/day. However, the relationship between the level of asthma control and increasing doses of Cic is unknown. This study investigated whether long-term treatment with higher doses of Cic would further improve asthma symptoms in patients with uncontrolled asthma despite ICS use. Patients and methods: In a double-blind, randomized, parallel-group study, 367 patients were allocated to one of three treatment arms (Cic 160, 320 and 640 μg/day). After a single-blind, 3-week baseline period with Cic 160 µg/day, eligible patients were randomized to receive 52 weeks of treatment with Cic 160, 320 or 640 μg/day (double-blind period) during which forced expiratory volume in 1 second (FEV1), exacerbations and Asthma Control Questionnaire (ACQ) scores were measured. Results: Treatment with all the three doses was associated with significant improvements in ACQ scores, FEV1 and asthma symptoms (P<0.01). There were no statistically significant differences between the three doses. The results of the primary end point analysis showed a numerical improvement in the ACQ score with Cic 640 μg/day compared with Cic 160 μg/day (least square [LS] mean: -0.122; two-sided P-value: 0.30). Post hoc subgroup analyses showed that the improvement in the ACQ score with Cic 640 μg/day compared with Cic 160 μg/day was statistically significant in subjects who experience at least one exacerbation per year (LS mean: -0.586; 95% confidence interval: -1.110, -0.062, P=0.0285). Adverse events were low and consistent with the known safety profile of Cic. Conclusion: In patients with persistent, uncontrolled asthma, increasing the Cic dose from 160 to 640 µg/day provided no clear additional effect. Patients who experience more than one exacerbation per year may benefit from higher doses; however, further studies are necessary to confirm this. All Cic doses were well tolerated. Keywords: dose-response, asthma control
PURPOSE: Reducing the risk of exacerbation is a long-term goal of managing moderate-to-severe asthma. The use of fluticasone propionate/formoterol fumarate dihydrate (FP/FORM) pressurized metered-dose (pMDI, Flutiform(®)), a type of inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) fixed-dose combination, has been associated with lower oral corticosteroid-requiring exacerbation rates than other ICS/LABA fixed-dose combinations, fluticasone propionate/salmeterol xinafoate (FP/SAL) and budesonide/formoterol fumarate (BUD/FORM). This study presents the first budget impact analysis of drug and exacerbation management cost savings associated with the increased access to FP/FORM compared to the currently available ICS/LABAs for treating moderate-to-severe asthma in Singapore. PATIENTS AND METHODS: A budget impact model showed changes to annual drug and exacerbation costs over 5 years for patients with moderate-to-severe asthma in Singapore, following the inclusion of FP/FORM on a government subsidy list. The eligible patient population was identified based on national statistics data. Different treatment costs pertaining to the population were applied according to the usage data (IQVIA Singapore National Sales Data) for different scenarios. Drug costs were obtained from public-sector hospitals. Exacerbation management costs were obtained from literature searches. RESULTS: The analysis showed that increased access to FP/FORM as a result of switching from FP/SAL could help achieve drug (S$1,042,289) and exacerbation management (S$223,550) cost savings over 5 years. In the scenario where patients switched from BUD/FORM, greater drug (S$2,572,797) and exacerbation management (S$256,781) cost savings were observed over 5 years. CONCLUSION: The analysis provides a perspective that the increased access to FP/FORM could help achieve drug and exacerbation cost savings for the treatment of moderate-to-severe asthma.
Sebastien Boisseau,1 Murtaza Qasuri,1 Weng Tong Ho,1 Wrik Ghosh,2 Yacine Hadjiat1 1Mundipharma Singapore Holding Pte Limited, Singapore; 2Costello Medical Singapore Pte Ltd, SingaporeCorrespondence: Yacine HadjiatMundipharma Singapore Holding Pte Limited, 12 Marina View, #22-01 Asia Square Tower 2, 018961, SingaporeTel +65 65111165Fax +65 65111167Email Yacine.Hadjiat@mundipharma.com.sgPurpose: Reducing the risk of exacerbation is a long-term goal of managing moderate-to-severe asthma. The use of fluticasone propionate/formoterol fumarate dihydrate (FP/FORM) pressurized metered-dose (pMDI, Flutiform®), a type of inhaled corticosteroid (ICS) and long-acting β 2 agonist (LABA) fixed-dose combination, has been associated with lower oral corticosteroid-requiring exacerbation rates than other ICS/LABA fixed-dose combinations, fluticasone propionate/salmeterol xinafoate (FP/SAL) and budesonide/formoterol fumarate (BUD/FORM). This study presents the first budget impact analysis of drug and exacerbation management cost savings associated with the increased access to FP/FORM compared to the currently available ICS/LABAs for treating moderate-to-severe asthma in Singapore.Patients and Methods: A budget impact model showed changes to annual drug and exacerbation costs over 5 years for patients with moderate-to-severe asthma in Singapore, following the inclusion of FP/FORM on a government subsidy list. The eligible patient population was identified based on national statistics data. Different treatment costs pertaining to the population were applied according to the usage data (IQVIA Singapore National Sales Data) for different scenarios. Drug costs were obtained from public-sector hospitals. Exacerbation management costs were obtained from literature searches.Results: The analysis showed that increased access to FP/FORM as a result of switching from FP/SAL could help achieve drug (S$1,042,289) and exacerbation management (S$223,550) cost savings over 5 years. In the scenario where patients switched from BUD/FORM, greater drug (S$2,572,797) and exacerbation management (S$256,781) cost savings were observed over 5 years.Conclusion: The analysis provides a perspective that the increased access to FP/FORM could help achieve drug and exacerbation cost savings for the treatment of moderate-to-severe asthma.Keywords: ICS/LABA, asthma exacerbation, treatment cost, Flutiform®, Fluticasone/formoterol, reimbursement
Aim: We investigated cost effectiveness of benralizumab vs. standard of care (SOC) plus oral corticosteroids (OCS) for patients with severe, eosinophilic OCS-dependent asthma in Sweden. Materials and methods: A three-state, cohort-based Markov model of data from three Phase III benralizumab clinical trials (ZONDA [NCT02075255], SIROCCO [NCT01928771], and CALIMA [NCT01914757]) was used to assess the incremental cost-effectiveness ratio of benralizumab vs. SOC plus OCS. Health outcomes were estimated in terms of quality-adjusted life-years (QALYs). The model included costs and disutilities associated with extrapolated OCS-related adverse events. Patients with severe asthma were defined as those receiving OCS >= 5 mg/day. Results: Benralizumab demonstrated a cost-effectiveness ratio vs. SOC plus OCS of 2018 Swedish Kronor (SEK) 366,855 (euro34,127) per QALY gained, based on increases of 1.33 QALYs and SEK 488,742 (euro45,344) per patient. Benralizumab treatment costs contributed most to incremental costs. The probability of benralizumab's being cost-effective with willingness-to-pay (WTP) thresholds between SEK 429,972 (euro40,000) and SEK 752,452 (euro70,000) ranged from 75% to 99%. Limitations: Potential limitations of these analyses include the use of combined data from three different clinical trials, a one-way sensitivity analysis that did not include mortality and transition estimates, and Observational & Pragmatic Research Institute (OPRI) data from the UK as a proxy of the Swedish health care system. Conclusions: The results of these analyses demonstrate that benralizumab has a high probability of being cost-effective compared with SOC plus OCS for a subgroup of patients with severe, eosinophilic asthma receiving regular OCS treatment and may support clinicians, payers and patients in making treatment decisions.
ObjectiveWe investigate the association between adult asthma and wealth, testing whether the disease impairs wealth accumulation (social selection model) or if wealth protects against asthma (social causation model).MethodsWe use the National Longitudinal Survey of Youth (n = 7,644) and linear and logistic regressions to estimate the association between wealth and asthma. Changes in relative wealth following an asthma diagnosis and asthma status by increases in wealth through inheritance provide evidence on the causal direction.ResultsAsthma, particularly severe asthma, is associated with lower wealth. Wealth ranking does not change after a diagnosis of asthma, but inheriting a substantial sum is associated with a lower risk of severe asthma.ConclusionWealth appears to protect against severe asthma, supporting the social causation model of disease.
