ABSTRACT
Introduction/Aim: Treatable traits based personalised medicine has been shown to improve outcomes in severe asthma clinic. We assessed the feasibility of a randomised controlled trial of protocolised 'focused' and 'extended' treatable trait guided asthma management in patients not under a severe asthma clinic. Method(s): Ten week single-group cohort study. Participants had a doctor's diagnosis of asthma, asthma control questionnaire (ACQ) score >1, and a history of exacerbation in the last year. Patients already under the care of a severe asthma clinic or receiving high-dose inhaled corticosteroids, biological therapy or maintenance oral corticosteroids were excluded. Intervention(s): asthma medication according to application of a 'focused' treatable trait algorithm, targeting type-2 inflammation and airflow obstruction. Feasibility outcomes: recruitment rates, acceptability of intervention, willingness to enrol in a full RCT, need for 'extended' trait assessment after 10 weeks, and estimation of trait prevalence. Result(s): Recruitment ceased after 14 months with 30/50 participants due to difficulties associated with COVID-19. 92% found the intervention acceptable and were willing to be randomised in a future study. 65% remained not well-controlled with an ACQ >1 after 10 weeks and would have required the 'extended' algorithm. Participants had a mean (SD) 4.8(2.3) of 13 traits assessed. Participation in the study was associated with clinically important improvements in ACQ, -1.0 (1.5) units;St George Respiratory Questionnaire, -15.1 (14.7) units;Asthma Quality of Life Questionnaire, +1.0 (1.1) units;and FEV1, +0.4 (0.4) L. Post-bronchodilator airflow obstruction reduced from 60% of participants at study commencement to 35%. 53% of participants were allocated continuous oral corticosteroids at some point during the study. Conclusion(s): Protocolised treatable trait management was acceptable, associated with significant clinical benefit and a full trial appears feasible. Targeting two traits was insufficient to control asthma in the majority of patients over the timeframe of this study, despite significant corticosteroid exposure.
ABSTRACT
Background: In our multi-disciplinary airways service, we assess refractory breathlessness due to suspected inducible laryngeal obstruction (ILO) and/or breathing pattern disorder (BPD). A significant proportion of patients have evidence of uncontrolled co-morbidity, including rhinitis and asthma, which aggravate airway symptoms. Aim(s): To identify the impact of rhinitis management on i) nasal symptoms ii) asthma control and iii) cough control, for individuals referred with suspected ILO +/- BPD and evidence of rhinitis. Method(s): Patient demographics/clinical data were collected between January 2021 and January 2022. Symptoms were recorded using the Total Nasal Symptom Score (TNSS), Asthma Control Questionnaire (ACQ) in those with asthma and a 10-point self-rating scale in chronic refractory cough (CRC). Result(s): Data were available for 43 patients [72% female, 18% atopic, median (IQR) age 54 (41-64) years] with symptoms of rhinitis, confirmed by nasendoscopy in 41% (not all patients had nasendoscopy due to COVID-19 pandemic). Co-morbidities included asthma 54% (39%, of whom were on biologic treatment), CRC (21%), ILO (35%) and BPD (35%). Rhinitis management comprised education (100%), nasal corticosteroids (91%), saline nasal douche (49%) and antihistamines (10%). TNSS scores improved [from 5 (4-6) to 3 (2-4), p<0.001] following intervention. In those with asthma, there was improvement in ACQ [2.98 (2.15-3.70) to 2.00 (0.95-3.05), p<0.001], and in those with chronic refractory cough in self-rating score [8 (4-9) to 2 (2-6), p=0.11]. Conclusion(s): Optimisation of medical treatment for individuals with rhinitis is important and can improve outcomes in patients with asthma, CRC, ILO and BPD.
ABSTRACT
SESSION TITLE: Imaging Across the Care Spectrum SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Eosinophilic airway inflammation and mucus plugs are common in asthma patients. Eosinophil depletion may reduce mucus plugging and improve airway patency and airflow distribution. This study will investigate the short-term benefits of sustained depletion of airway eosinophils by benralizumab, an anti-IL-5Rα monoclonal antibody, on airway structure and dynamics using functional respiratory imaging (FRI) in adults with severe eosinophilic asthma (SEA). METHODS: A multicenter, single-arm, open-label, phase 4 study enrolling approximately 138 patients. Screening will be followed by a run-in period of up to 21 days, before administration of subcutaneous benralizumab 30 mg at Weeks 0, 4 and 8, final assessment at Week 13, and a 2-week follow-up period. RESULTS: Key inclusion criteria: age 18-70 years with diagnosed SEA inadequately controlled by high-dose inhaled corticosteroid and long-acting β2-agonist (ICS-LABA) treatment +- oral corticosteroids (OCS) or other asthma controllers;documented post-bronchodilator (BD) reversibility;≥2 exacerbations in prior 12 months;baseline peripheral blood eosinophil count ≥300/μL (≥150 cells/μL if OCS-dependent);pre-BD forced vital capacity (FVC) <65% predicted, pre-BD FEV1 <80% predicted and Asthma Control Questionnaire (ACQ-6) ≥1.5. Key exclusion criteria: exacerbation/pulmonary infection 6 weeks pre-screening;smokers or ex-smokers who stopped smoking ≤12 months pre-screening and/or history of >10 pack-years;positive for COVID-19 at or ≤6 weeks before screening, or severe COVID-19 at any time.The primary endpoint is mean change from baseline in specific airway volume measured at total lung capacity. Secondary objectives include change from baseline in airway dynamics (lung, airway and blood vessel volumes, airflow distribution, airway resistance, air trapping, ventilation/perfusion mapping) and mucus plug scores, and correlations with conventional lung function measurements (FVC, FEV1) at baseline and Week 13. FRI will be via computed tomography scans assessed using computer modelling. Exploratory objectives include: relationships between airway dynamics and patient-reported outcomes (PROs) such as the Asthma Impairment and Risk Questionnaire (AIRQ), ACQ-6, and St George's Respiratory Questionnaire (SGRQ) at baseline, from baseline to Week 13, and change from baseline in Central/Peripheral (C/P) lung deposition ratio of inhaled drugs. Safety and tolerability will also be assessed. CONCLUSIONS: This study will advance understanding of the eosinophil-depletion effects of benralizumab on airway structure, dynamics, and mucus plugs and could provide additional useful insights into the relationship of PROs with changes in airway dynamics and structure. CLINICAL IMPLICATIONS: Our results may help further characterize physiologic changes resulting from eosinophil depletion with benralizumab and better delineate the impact of changes in lung function and structure on PROs. DISCLOSURES: stockholder relationship with AstraZeneca Please note: 2 years Added 03/31/2022 by Donna Carstens, value=Salary No relevant relationships by Wilfried De Backer Employee relationship with AstraZeneca LP Please note: Since 2014 by Eduardo Genofre, value=Salary Shareholder relationship with AstraZeneca LP Please note: Since 2014 by Eduardo Genofre, value=LTIs Employee relationship with FLUIDDA Inc Please note: Aug 2021 - Present Added 04/12/2022 by Patrick Muchmore, value=Salary Advisory Committee Member relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Consultant relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with AstraZeneca Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/20 2 by Reynold Panettieri Advisory Committee Member relationship with RIFM Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Consultant relationship with RIFM Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Equillium Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Equillium Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Genetech Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with Genetech Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with Sanofi/Regeneron Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Consultant relationship with Bayer Please note: 24 months by Reynold Panettieri, value=Honoraria Advisory Committee Member relationship with Theravance Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with Novartis Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Contracted Research relationship with Optikira Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Medimmune Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Contracted Research relationship with Maven Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Contracted Research relationship with Evelobio Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Contracted Research relationship with Johnson & Johnson Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with AstraZeneca;RIFM;Equillium;Genentech;Thervance Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Consultant relationship with AstraZeneca;RIFM;Equillium;Bayer Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with AstraZeneca;Sanofi/Regeneron;Genentech Please note: 24 months by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Research grant recipient relationship with Novartis;Optikira;Medimmune;Maven;Evelobio Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Research grant recipient relationship with Johnson & Johnson;AstraZeneca;RIFM;Equillium;Genentech Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Research grant recipient relationship with Theravance Please note: 24 months by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with AstraZeneca Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with AstraZeneca Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with AstraZeneca Please note: $1001 - $5000 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with MedImmune Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 0 /29/2022 by Reynold Panettieri Principal Investigator relationship with MedImmune Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Reseaerch Institute for Fragrance Materials Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with Reseaerch Institute for Fragrance Materials Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Equillium Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with Equillium Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Theravance Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Removed 03/29/2022 by Reynold Panettieri Advisory Committee Member relationship with Avillion Please note: $1001 - $5000 by Reynold Panettieri, value=Consulting fee Speaker/Speaker's Bureau relationship with Sanofi/Regeneron Please note: $1001 - $5000 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Speaker/Speaker's Bureau relationship with Genentech Please note: $1001 - $5000 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationship with Genentech Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Principal Investigator relationshipwith OncoArendi Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Metera Please note: $20001 - $100000 by Reynold Panettieri, value=Grant/Research Support Removed 03/29/2022 by Reynold Panettieri Consultant relationship with TEVA Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Removed 03/29/2022 by Reynold Panettieri Consultant relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Advisory Committee Member relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Speaker/Speaker's Bureau relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with AstraZeneca Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Consultant relationship with RIFM Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Advisory Committee Member relationship with RIFM Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with RIFM Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Advisory Committee Member relationship with Genentech Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with Genentech Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Consultant relationship with TEVA Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Principal Investigator relationship with TEVA Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Equillium Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Novartis Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Medimmune Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator r lationship with Origo Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with ACTIV-1 Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Janssen Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Principal Investigator relationship with Vault Health Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Grant/Research Support Speaker/Speaker's Bureau relationship with Sanofi Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Speaker/Speaker's Bureau relationship with Merck & Co Please note: 24 months Added 03/29/2022 by Reynold Panettieri, value=Honoraria Employee No relevant relationships by Vivian Shih Shareholder relationship with AstraZeneca Please note: >5 years by Frank Trudo, value=Shares
ABSTRACT
It is hard to make a conclusion about relationship between Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Bronchoobstructive Syndrome (BOS) in the postcovid period based on the literature. The aim. To determine the optimal treatment approaches by conducting a comprehensive assessment of clinical, laboratory and functional parameters, taking into account the risk factors for the development of BOS. Methods. 10,456 patients with Coronavirus Disease-19 (COVID-19) were examined, and 7,459 patients were randomized into 2 groups with a newly diagnosed BOS. Group 1 (n = 3,245) was prescribed beclomethasone/formoterol (BDP/FORM) as Maintenance And Reliever Therapy (MART). Group 2 (n = 4,252) was prescribed budesonide suspension (BUD) and salbutamol solution (SAL). The study assessed severity of COVID-19, presence of atopy and frequency of acute respiratory viral infections (SARS) in the medical history, spirometric parameters, blood eosinophils, Asthma Control Questionnaire-5 (ACQ-5) score, use of pro re nata medications, and adverse events. Results. Patients who had mild COVID-19 were diagnosed with BOS at weeks 8 – 24 (73.3%), while patients with moderate or severe COVID-19 were diagnosed at week 4 (54.9%). Virus-induced BOS (VI BOS) was diagnosed in 71.8% of the cases. 13% of the patients with BOS in postcovid period were diagnosed with asthma. Conclusion. The incidence of BOS is significantly higher in patients with atopy and history of frequent SARS who had moderate or severe COVID-19. A fixed combination of extrafine BDP/FORM as MART was superior to nebulized BUD + SALM in the treatment of VI BOS.
ABSTRACT
RATIONALE: Around 4.6 million people in the United Kingdom (UK) have asthma, with an estimated 5.7% treated for severe asthma. Benralizumab is indicated for the treatment of severe eosinophilic asthma (SEA) in adults inadequately controlled despite appropriate maintenance therapy. The Connect 360 Patient Support Programme (PSP) for patients on benralizumab includes options for home-based drug administration, education and adherence support by trained nurses - of particular relevance during the COVID-19 pandemic. Limited evidence exists on the benefit of PSPs for asthma patients or those administering biological therapies at home. This study aims to describe patient characteristics, key outcomes and experience with the PSP using UK data from Connect 360. METHODS: A non-interventional, retrospective cohort study of patients, enrolled in the PSP (Oct-2019 onwards) and consenting to the use of personal data for research purposes (“study cohort”). Patients opting for additional support services with at least one nurse interaction within described study timeframes formed the clinical cohort. Patients were observed up to 48 weeks post-PSP enrolment (interim data taken on 31-Mar-2021;data collection ongoing) with study endpoints assessed at baseline (0-4 weeks), 24 (±4) weeks and 48 (±8) weeks post-PSP enrolment. Characteristics at enrolment are described for the study cohort. Patient-reported clinical outcomes (hospitalisations, maintenance oral corticosteroid [mOCS] use, Asthma Control Questionnaire [ACQ-6] scores) and service satisfaction (1-5 point scale, 5 being most satisfied) were analysed where available from routine PSP nurse calls/visits. Analysis was descriptive;Kaplan-Meier estimators were used to estimate PSP discontinuation rates. RESULTS: The study cohort was 611 patients (mean enrolment age: 54.1 years, 63.2% female [N=323]). Most (98.9%) were benralizumab users on maintenance dosing (8-weekly) at enrolment. The clinical cohort consisted of 149 (baseline), 175 (24 weeks) and 195 (48 weeks) patients. PSP discontinuation rates were 4.4% and 11.6% at 24 and 48 weeks. Proportion of patients reporting mOCS use was 49.7%, 44.0% and 32.8% at each timepoint and hospitalizations were 10.9% and 4.1% at 24 and 48 weeks. Mean ACQ-6 scores decreased over time. Mean (SD) satisfaction scores were 4.6 (0.7) and 4.8 (0.5) at 24 and 48 weeks, respectively. (Table 1). CONCLUSIONS: Overall patients' experience with the PSP was positive, evidenced by high satisfaction with and persistence to the PSP. Where data were available, proportion of patients reporting mOCS and hospitalizations at 48 weeks were numerically lower than previous timepoints and mean ACQ-6 scores improved, suggesting a positive impact of benralizumab treatment within the PSP.
ABSTRACT
INTRODUCTION: Only little is known about COVID-19 in patients with asthma. There is no data on COVID-19 in patients with severe asthma or patients with asthma who are treated with monoclonal antibodies. CASE STUDY: Here, we present the case of a severe eosinophilic asthmatic in whom benralizumab treatment, an anti-IL-5R monoclonal antibody, was initiated 2 years ago. Prior to benralizumab treatment, every viral infection had resulted in a prolonged course of oral corticosteroids (OCS). Since initiation of benralizumab, the patient has had good asthma control. Mid-March 2020, the patient developed high fever. RESULTS: A SARS-CoV-2-PCR (nasopharyngeal swab) was positive. The patient's symptoms subsided after few days. No OCS was needed. The asthma control questionnaire 6-item scale worsened moderately in the week of the infection and returned to normal levels thereafter. The asthma control test, measuring longer term asthma control, showed no decline. CONCLUSION: The course of COVID-19 was very mild in this particular patient with severe eosinophilic asthma. So far, there is no evidence that would suggest a more severe course of COVID-19 in patients with asthma. It is worth noting, that prior to the initiation of benralizumab this patient had multiple exacerbations per year triggered by viral infections (4/year), which all required OCS. Whilst only anecdotal, this case study provides the first evidence to support the current recommendation of continuing monoclonal antibodies in patients with severe asthma during the COVID-19 pandemic.