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Background: COVID-19 disease caused by SARS-CoV-2, has changed life as we know it, causing millions of deaths worldwide. Reported risk factors for mortality include advanced age, obesity, hypertension, diabetes mellitus, and chronic obstructive pulmonary disease. Although asthma is a chronic obstructive disease, most evidence reveals a protective effect between asthma, eosinophilia and COVID-19. La Paz University Hospital, in Madrid, has developed one of the largest cohorts in Europe, with more than 3500 patients with COVID-19. Our aim was to evaluate post-COVID-19 evolution at 6 and 12 months in asthmatic patients. Method(s): We selected the asthmatic patients in this cohort. We obtained information from their clinical history, including sex, age and comorbidities. We classified patients by T2 or non-T2 asthma and collected pre-COVID19 information: treatment, control (measured by asthma control test (ACT) and number of exacerbations), pulmonary lung function, eosinophils in blood and immunoglobulin E levels. Post-COVID-19 data after 6 and 12 months were recorded: symptoms (chest pain, cough, expectoration and dyspnea), ACT, number of exacerbations, the need to intensify the asthma treatment, and the pulmonary lung function. Result(s): Significant association was found between COVID-19 pneumonia in asthmatic patients and the risk of having chest pain after 6 months (p = 0.009). Fewer eosinophilic count was associated with dyspnea 6 months post-covid (p = 0.043). Asthmatic smokers had an increased risk of thromboembolism 12 months after COVID-19 (p = 0.025). Although significant association standards were not met nor demonstrated, thoracic pain was more frequent 6 months post-COVID-19 in non-T2 asthmatic patients (44.4%) than T2 patients (20.3%) (p = 0.064). Eosinophilic asthma (eosinophil counts higher than 250/ mcl), presented lower prevalence of chest pain 12 months post-COVID-19 (p = 0.081). Conclusion(s): This is the first study that demonstrates the association between risk of chest pain and dyspnea after 6 months in asthmatic patients with COVID-19 pneumonia. It was also found that if these patients smoked, there was an increased risk of thromboembolism at 12 months. Further studies, with a higher number of patients are needed to explore deeply the impact of COVID-19 in asthma outcomes.
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Background: Rhinovirus is the most common trigger for exacerbations of asthma. Alveolar macrophages (AM) are a major site of RV infection and can also be infected by SARS-CoV-2. The pandemic caused by the SARS-CoV-2 raised concerns that patients with severe asthma (SA) would be at particularly high risk of developing severe disease. To date, evidence for poor outcomes in asthma remains limited suggesting a differential immune response to these two viruses. Method(s): Alveolar macrophages (AM) were isolated from bronchoalveolar lavage samples from patients with SA and infected with RV (n=13), SARS-CoV-2 alpha (B.1.1.7) (n=9) and delta (B.1.627.2)(n=8) variants. Antiviral mediators representing NF-KB-induced interferon-driven mRNAs (IL6 and IL8, RIGI and MDA5, respectively) were measured by qPCR, normalised to GAPDH and compared between infected AM and controls. Result(s): RV infected AM showed significant increases in mRNA expression of RIGI (4.39 fold change +/-4.68, p<0.001 vs control), MDA5 (2.96 fold change +/- 2.93, p=0.002 vs control) and IL6 (1.88 fold change +/- 0.98, p=0.006) compared to AM treated with control media alone, whilst IL8 did not significantly change. However, AM infected with SARS-CoV-2 alpha or delta variants showed no difference in levels of antiviral mediators compared to controls. Longitudinal analysis of AMs infected with SARS-CoV-2 alpha or delta variants showed no antiviral response. Conclusion(s): AM from subjects with severe asthma produce a pattern of anti-viral responses following RV infection that is absent when exposed to SARS-CoV-2 variants currently in circulation.
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99441 – [Telephone evaluation and management service by a physician or other qualified healthcare professional who may report evaluation and management services provided to an established patient, parent, or guardian not originating from a related E/M service provided within the previous seven days nor leading to an E/M service or procedure within the next 24 hours or soonest available appointment;Five-10 minutes of medical discussion.] Cellular Partners of Mast Cells and Basophils in Homeostasis and Allergic Disease You can find a full list of 2020 Virtual Annual Meeting sessions, including pricing for special sessions, by visiting the AAAAI Continuing Education Center at education.aaaai.org.Earn CME Credit with Select AAAAI Podcast Episodes The AAAAI is excited to offer free CME credit for members who listen to select episodes of our podcast, Conversations from the World of Allergy. Episodes offering CME credit will be identified with a CME icon and CME language in the podcast description.Lay Organizations The AAAAI places a high value on its relationships with patient advocacy organizations in support of our mutual concern for the needs of people with allergy, asthma and immunologic disease and their families. Allergy & Asthma Network allergyasthmanetwork.org American Partnership for Eosinophilic Disorders (APFED) apfed.org Asthma & Allergy Foundation of America (AAFA) aafa.org Alaska Chapter: aafaalaska.com California Chapter: aafa-ca.com Greater Kansas City Chapter: aafakc.org Maryland/Washington DC Chapter: aafa-md.org Michigan Chapter: aafamich.org New England Chapter: asthmaandallergies.org Texas Chapter: aafatexas.org St. Louis Chapter: aafastl.org Campaign Urging Research for Eosinophilic Disease (CURED) curedfoundation.org Food Allergy and Anaphylaxis Connection Team (FAACT) foodallergyawareness.org Food Allergy Research & Education (FARE) foodallergy.org Immune Deficiency Foundation (IDF) primaryimmune.org International FPIES Association fpies.org The Mastocytosis Society (TMS) tmsforacure.org US Hereditary Angioedema Association (HAEA) haea.org You Can Now Use Our Internet Point-of-Care Activity to Earn MOC The COVID-19 pandemic has altered the way we see patients and conduct research.
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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
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.
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Introduction:Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). We have previously identified that a suboptimal response to the eosinophil targeting anti-IL5/5R mAbs mepolizumab and benralizumab is seen in 27% and 14% of patients with SEA respectively1,2. The mechanism of this is not well-understood. It is unknown whether such patients respond in a clinically meaningful way following a switch to dupilumab. Methods:We performed a retrospective analysis of the clinical effectiveness of dupilumab (minimum 6 months treatment) in patients with SEA at our tertiary severe asthma centre who had failed to adequately respond to at least one of the anti-IL-5/5R mAbs. Change in the annualised exacerbation rate (AER), maintenance oral corticosteroids (mOCS) requirements, ACQ-6 and mAQLQ was recorded. Results:Thirty-two patients (mean age 41.2, 68.8% female, 71.9% atopic) were included in the analysis. 13/32(40.6%) had co-morbid nasal polyposis and 5/32(15.6%) had eczema. The baseline FeNO was 60ppb(IQR 39.6-87.5) and peak eosinophil count prior to any mAb was 0.6(IQR 0.5-0.9). 23/32(71.8%) were switched from benralizumab, of whom, 12/23(52.2%) had also failed to respond to at least one other anti-IL5 mAb previously. At six months, the daily median mOCS dose in those requiring mOCS at baseline (n=18) fell from 10mg(IQR 5-25mg) to 3mg(IQR 0-5mg), p≤0.001. 4/18(22%) were able to stop mOCS completely. Mean(SD) AER improved from 2.34(1.89) to 0.44(0.95), p≤0.001. There were also significant improvements in ACQ6 and mAQLQ that exceeded twice the MCID for both measures: mean (SD) ACQ6 improved from 3.04(1.26) to 1.82(1.28), p≤0.001;mAQLQ improved from 3.90(SD 1.40) to 5.36(SD 1.05), p≤0.001. Due to the COVID-19 pandemic, FEV1 data was only available for 8 patients. However, there was nonetheless a significant rise in FEV1 (%predicted) from 55.6% (9.78) to 68.5%(16.9), p=0.011. One patient discontinued dupilumab during the follow-up period. Conclusion: A minority of individuals with SEA have a suboptimal response to eosinophil targeted therapy with an anti-IL5/5R mAb. In these patients, we report significant clinical improvements following initiation with dupilumab suggesting an important role for the IL-4/-13 pathway in these patients. Further research is required to understand whether these patients represent a distinct subphenotype of T2-high asthma.
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Introduction: The increase in drugs available for severe uncontrolled asthma and the lifestyle of these patients make it necessary to implement self-administration programs of these therapies at home. Benralizumab, a monoclonal antibody targeting IL5R, was authorized in Spain for poorly controlled severe eosinophilic asthma. The possibility of administration at home was approved in March 2020 in Spain. The aim of the Auto-Benra study was to evaluate the usability and satisfaction of the benralizumab prefilled syringe and autoinjector and assessing the effectivity of these devices in uncontrolled severe eosinophilic asthma (SEA) in home-self administration. Methods: This is a retrospective, observational multicenter study uncontrolled SEA patients treated with benralizumab at least with 3 doses self-administered at home before April 30, 2021. Reliability and satisfaction with benralizumab at home were evaluated with subcutaneous administration assessment questionnaire (SQAAQ) and visual analogic scales (VAS). Effectiveness was evaluated in all patients with asthma control test (ACT), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), annual exacerbation rate, oral corticosteroid treatment (OCS) and asthma-related hospitalizations and emergency visits. Results: Fifty-four patients across 9 hospitals in Spain were included. The mean SQAAQ score was 6.89 (±0.16) points. Patients and their caregivers and doctors report excellent satisfaction by VAS, with no differences between benralizumab devices used (prefilled syringe and autoinjector). Severe exacerbation rate decreased by 65% (p = 0.0007) after benralizumab treatment. ACT score improved on average 6.27 ± 5.35 points (p < 0.0001) and the mean MiniAQLQ increased up to 1.58 ± 1.47 points (p < 0.0001). Twenty-four patients were OCS-dependent and at the end of study 14 patients get complete OCS withdrawal. Conclusion: AUTO-BENRA study supports the use of benralizumab at home given the excellent results of satisfaction and usability by patients and their caregivers.
ABSTRACT
We report a case of a patient affected by severe eosinophilic asthma with nasal polyps (SEA+NP) who developed coronavirus disease 2019 (COVID-19) six months after starting benralizumab as add-on therapy. Both SEA and NP were under control with no exacerbations at the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient was hospitalized for four months, during which the treatment with benralizumab was interrupted. Despite the onset of bilateral interstitial pneumonia, developed as a consequence of the SARS-CoV-2 infection, the patient was discharged without complications, with a significant improvement in the chest CT scan following the administration of systemic corticosteroids (SCS) and low-flow oxygen therapy. The treatment with benralizumab was reintroduced at the regular dosing regimen immediately after his discharge. Lung function was assessed three months after the discharge and showed normal levels as before the development of COVID-19 symptoms. A long-term follow-up after 26 months from the introduction of benralizumab showed a normal lung function and well-controlled asthma, without exacerbations or the need for corticosteroid bursts.
ABSTRACT
Benralizumab is a humanized, afucosylated IgG1k monoclonal antibody directed against the α subunit of IL-5R. It inhibits IL-5, the main regulator of the biology of eosinophils, from binding to its specific receptor. Moreover, it directly targets and depletes eosinophils and other IL-5R + cells by inducing antibody-dependent cell-mediated cytotoxicity, differentiating it from the other IL-5 ligand targeted therapies. We report a case of a 61-year-old woman with severe eosinophilic asthma and rhinosinusitis, referred to our department in 2014. Blood eosinophilia (560 cells/μL) and normal total IgE levels (57 kU/L) were present. She was on GINA step-5 treatment with additional aminophylline 225mg twice daily. Control was not achieved despite good compliance with frequent asthma exacerbations requiring emergency department visits, multiple systemic corticosteroid courses and hospitalizations. Maintenance therapy with prednisolone 5mg daily was attempted with only a slight improvement. Although no more hospitalizations were required, she continued to have several asthma exacerbations. Treatment with subcutaneous Benralizumab 30mg was started in October 2020. The subsequent administration was skipped because the patient had COVID-19. An interval of approximately 3 months (82 days) separated the first 2 administrations. Regardless of our recommendation, the patient decided to discontinue systemic corticosteroids and aminophiline. Evaluation before the 2nd administration showed that blood eosinophils decreased to 0 cells/μL and clinical improvement that was established by disease control and health-related quality of life questionnaires (see table I) Although maintained eosinopenia after an isolated intravenous administration of Benralizumab has been reported, to our knowledge this is the first case related to a single subcutaneous administration in a previously eosinophilic patient. Additionally, clinical improvement was sustained in spite of stepping down her maintenance therapy. This case raises questions regarding the possibility and success of patient-oriented scheduling of Benralizumab administration as an alternative to the current treatment regimen. (Table Presented).
ABSTRACT
Background: Under the restriction of direct access to specialized health care, COVID-19 pandemic, has created an “iceberg” regarding disease control data in severe Bronchial Asthma (BA). We aimed to evaluate indicators of asthma control, in severe persistent BA, consequences of pandemic and in-person visits limitations among this patient population. Method: A cross-sectional study, obtained data from 86 patients with yearly pre-pandemic hospitalizations, at the only tertiary hospital center for severe persistent BA in Albania. Descriptive data analysis was performed through anamnestic and clinical records. Standardized and validated questionnaires for inhalers adherence and asthma control, have been performed though phone interview during January 2021. Patients under treatment with biologic drugs (anti-IgE) and allergen specific immunotherapy have been excluded. Results: 64% were classified as high TH2 phenotype, predominating late-onset eosinophilic asthma (30.2%), and in low TH2 phenotype, with predominance of obesity associated asthma (18.6 %). 66,3 % were females with mean age of 49.3 ± 13.9. Overall Asthma Control Test (ACT= 19.5 ± 3.8), 43% controlled (20-25 points), with no statistically significant differences, between sex and phenotypes. Among early onset allergic asthma phenotype (25,6%), lower ACT score (18.5 ± 1.5) resulted in outdoor + indoor allergen polysensitization, compared to monosensitization (p < 0.05). Seasonal influenza vaccination rate was 16.2%, ACT score between vaccinated and unvaccinated groups, with significant difference (p = 0.03). Prevalence of confirmed COVID-19 was 15.1%, only 1,2% severe. ATC score, between confirmed or suspected post COVID-19 severe ABs and COVID-19 negative, was not statistically significant. Coexistence of sporadic and intentional nonadherence affected ACT score (p = 0.01), between controlled (ACT, 20-25) and uncontrolled group (ACT<20 points). Conclusion: Asthma control in severe persistent BA population was <50%, affected by sensitization profile, seasonal flu vaccination and type of non-adherence to inhalers. Differences of disease control in ACT score, were not statistically related with phenotype, sex or post COVID-19 infection condition. Particularly, Severe Persistent Bronchial Asthma needs a periodic specialist care to reach disease control and to lower the burden of indirect pandemic effects on disease progression.
ABSTRACT
In 2012 a 25-year-old man presented to our outpatient clinic for severe atopic dermatitis (AD) and severe allergic eosinophilic asthma in polisensitivity (house dust mite, cat, gramineous plants, birch, milk protein and, in particular, Alternaria). His clinical history was also characterized by gastro-esophageal reflux disease and chronic rhinitis without polyposis, with septal deviation and turbinate hypertrophy, worthy of surgical intervention. History taking revealed egg and cow milk protein allergy and severe asthma since the first months of life, with frequent hospital admissions due to exacerbations. AD was severe and diffuse, involving especially face, neck, back and superior limbs, often complicated by impetigo. The esthetic, social and psychological impact led him to quit his job as a barman. At presentation, the Eczema Area and Severity Index (EASI) score was 72/72. Laboratory tests showed eosinophilic count ranging between 1.060 and 2.140/mm3, and high serum levels of total Immunoglobulin E (5.939 kUI/L). Tryptase levels were normal and autoantibody analysis was negative. Parasite stool examination was negative. Nasal swab tested positive for Staphylococcus aureus, which was treated with Sulfamethoxazole-Trimethoprim. Asthma Control Test was 15/25, pulmonary function tests (PFTs) showed mild obstruction (FEV1 4.43 L, 103%, FEV1/FVC 69%), with positive bronchodilator testing (FEV1 5.12 L, + 670 mL, + 16%). Firstly, he was treated with topical steroids and sometimes with oral corticosteroids, with poor response. Then, in July 2019, he initiated therapy with cyclosporine 3-5 mg/kg. Soon, the drug had to be discontinued due to adverse effects (gastrointestinal symptoms and infections). In November 2019, at the age of 32 years, he started therapy with monoclonal antibody anti-IL-5 receptor alpha (benralizumab 30 mg 1 subcutaneous vial every 4 weeks for the first three administrations and then every 8 weeks), with a terrific clinical improvement of AD since the first administrations and with benefit on asthma control (ACT after the first administration increased up to 25/25;PFTs could not be performed, due to SARS-CoV-2 pandemic). This therapy has always been well tolerated. The eosinophilic count decreased to 0/mm3 after the first administration. At the moment, after one year of therapy, AD is almost fully disappeared (EASI SCORE 4/72), despite being in free diet, and the quality of life of the patient has definitely improved.
ABSTRACT
Background: Mepolizumab, a humanized monoclonal antibody against IL-5, is a therapeutic option in patients with severe eosinophilic asthma. Its efficacy has been shown in clinical trials. Our aim is to present data from our center to corroborate this evidence in the complexity of real-life patients. Method: A retrospective study of patients with severe eosinophilic asthma treated with mepolizumab in our center was performed. We collected data regarding demographics, eosinophilic blood count, FEV 1 , fractional exhaled nitric oxide (FeNO), clinically significant exacerbations [need to start or increase oral corticosteroids (OCS), emergency department visit and/or hospitalization], OCS and safety profile, before and after patients started mepolizumab. Results: A total of 12 patients were included (9 female, mean age 53.7 ± 8.9 years old);10 patients had concomitant chronic rhinosinusitis with nasal polyps. Mepolizumab was administered in a dose of 100 mg every 4 weeks, except for 2 patients diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) (300 mg every 4 weeks). The mean duration of treatment was 13.75 months [3 - 28 months]. Due to COVID-19 pandemics restriction it was not possible to assess absolute eosinophilic count in 2 patients, as well as FeNO and FEV 1 in 2 different patients after treatment. The mean value before and after treatment for each outcome were the following: absolute eosinophilic blood count, from 537.5/μl to 116/μl ( p = 0.005);FEV 1 , from 1.44L to 1.84L ( p = 0.036);FeNO, from 62.27ppm to 41.8ppm ( p = 0.260);clinically significant exacerbations, from 2.83 in the previous year to 0.25 ( p = 0.007). Prior to treatment, 8 patients were treated with daily OCS, and after starting mepolizumab 3 of them were able to stop OCS and the others reduced daily dose (mean dose reduction 64.7%, ranging from 25% to 98.5%). The only side effect reported was sporadic headache, and no one discontinued treatment. Conclusion: In our sample, we observed a significant reduction in eosinophilic blood count, clinically significant exacerbations and OCS use, as well as improvements in FEV 1 , in patients with severe eosinophilic asthma treated with mepolizumab, with a good safety profile. This information supports data from clinical trials and early real-life experience in other populations.
ABSTRACT
Severe asthma can be associated with eosinophilic or allergic phenotypes or both. Eosinophilic inflammation is associated with exacerbations and disease severity due to biological activity of interleukin-5 (IL-5). Patients with severe asthma have reported reduced lung function and poor health-related quality of life (HRQoL) and may require systemic corticosteroids for its management. Thus, treatment targeting IL-5 can help improve quality of life and reduce the use of systemic corticosteroids in severe asthma. Mepolizumab is approved for treating severe eosinophilic asthma as it helps reduce exacerbations, improve lung function and asthma control, and reduce the use of systemic glucocorticoids. This further helps in enhancing HRQoL of these patients. This case series includes four adult patients suffering from severe eosinophilic asthma who were treated with mepolizumab.