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1.
Chest ; 162(4):A2652-A2653, 2022.
Article in English | EMBASE | ID: covidwho-2060978

ABSTRACT

SESSION TITLE: Late Breaking Insights In Management of Asthma and COPD SESSION TYPE: Original Investigations PRESENTED ON: 10/18/2022 09:15 am - 10:15 am PURPOSE: SARS-CoV-2 vaccines have greatly reduced the impact of the COVID-19 pandemic. However, immune responses and their ability to protect against SARS-CoV-2 infection and severe clinical outcomes vary amongst vaccinees. Understanding who remains at high risk for severe infection despite vaccination and who may need additional vaccine boosters is critical for the control of this and future pandemics. We recently reported a reduced humoral immune response after mRNA SARS-CoV-2 vaccination in patients with severe asthma or atopic dermatitis on biologic therapies three months after the second vaccination, compared to healthy controls. The purpose of this study is to characterize the immune response of these patients six months after vaccination. METHODS: We conducted a prospective observational trial from February 2021 to February 2022 and enrolled 77 adults with severe asthma or atopic dermatitis treated with benralizumab, mepolizumab or dupilumab, receiving a SARS-CoV-2 mRNA vaccination, in addition to 45 healthy controls. We analyzed pseudovirus neutralization against wild-type, Delta variant and Omicron variant SARS-CoV-2, using a pseudotyped lentivirus. RESULTS: After excluding patients with prior COVID-19 or significant immunosuppression, we analyzed 28 patients (5 patients on benralizumab, 20 patients on dupilumab, 3 patients on mepolizumab) in addition to 34 healthy controls at 6 months after vaccination. We found that patients with severe asthma or atopic dermatitis treated with biologics had lower pseudovirus neutralization titer at 6 months, compared to healthy controls. The mean 50% inhibitory dilution against wild-type SARS-CoV-2 among patients on biologics were lower at 2.313 log10 compared to 2.743 log10 in the healthy control group, p-value <0.0001. Additionally, the patients on biologics had lower neutralizing antibody titers against Delta variant and Omicron variant SARS-CoV-2. CONCLUSIONS: Our data shows that patients with severe asthma or atopic dermatitis on biologic therapies have lower neutralization titer after SARS-CoV-2 mRNA vaccination compared to healthy controls 6 months after the second vaccination. Large population studies have recently shown that severe or active asthma is associated with worse COVID-19 outcomes and several studies have shown that lower humoral immunity after vaccination is associated with less protection against disease. It is therefore critical to provide booster vaccinations to these vulnerable patients. CLINICAL IMPLICATIONS: Clinicians should encourage patients with severe asthma or atopic dermatitis on biologic therapies to receive SARS-CoV-2 booster vaccinations as they may unknowingly remain at high risk for severe disease. DISCLOSURES: No relevant relationships by Fabliha Anam No relevant relationships by Suneethamma Cheedarla No relevant relationships by Narayanaiah Cheedarla No relevant relationships by John Daiss No relevant relationships by Natalie Haddad No relevant relationships by Ian Hentenaar No relevant relationships by Fernando Holguin No relevant relationships by Caroline Kim No relevant relationships by Pedro Lamothe No relevant relationships by Frances Lee No relevant relationships by ANDREW NEISH No relevant relationships by wendy neveu No relevant relationships by Rahulkumar Patel No relevant relationships by Carmen Polito No relevant relationships by Richard Ramonell No relevant relationships by Mayuran Ravindran No relevant relationships by John Roback No relevant relationships by Martin Runnstrom Consultant relationship with BLI, Inc. Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Royalty Consultant relationship with Bristol Meyers Squibb/Celgene Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee Speaker/Speaker's Bureau relationship with Bristol Meyers Squibb/Celgene Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=H noraria Consultant relationship with GlaxoSmithKline Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee Speaker/Speaker's Bureau relationship with GlaxoSmithKline Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Honoraria Consultant relationship with Janssen Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee Speaker/Speaker's Bureau relationship with Janssen Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Honoraria Consultant relationship with Visterra Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee Speaker/Speaker's Bureau relationship with Visterra Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Honoraria Consultant relationship with Kyverna Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee No relevant relationships by Sunita Sharma No relevant relationships by Colin Swenson No relevant relationships by Robert Swerlick

2.
Chest ; 162(4):A1-A5, 2022.
Article in English | EMBASE | ID: covidwho-2060532

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

3.
Case Reports in Dermatology ; 14(2):203-209, 2022.
Article in English | ProQuest Central | ID: covidwho-2027180

ABSTRACT

TEN/DRESS overlap syndrome can be difficult to diagnose, especially if it is masked by comorbidities in critically ill patients in intensive care units. The existing therapy for the two conditions is also a major challenge for the treating team. A possible alternative, especially for refractory cases, is benralizumab as an IL-5-receptor alpha-chain-specific humanized monoclonal antibody (IgG1k). We are able to show a successful treatment in this case report.

4.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927860

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.

5.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927846

ABSTRACT

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.

6.
J Allergy Clin Immunol Pract ; 10(10): 2588-2595, 2022 10.
Article in English | MEDLINE | ID: covidwho-1907243

ABSTRACT

BACKGROUND: At the beginning of the pandemic, there have been considerable concerns regarding coronavirus disease 2019 (COVID-19) severity and outcomes in patients with severe asthma treated with biologics. OBJECTIVE: To prospectively observe a cohort of severe asthmatics treated with biologics for the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and disease severity during the COVID-19 pandemic. METHODS: Physicians from centers treating patients with severe asthma all over Greece provided demographic and medical data regarding their patients treated with biologics. Physicians were also asked to follow up patients during the pandemic and to perform a polymerase chain reaction test in case of a suspected SARS-Cov-2 infection. RESULTS: Among the 591 severe asthmatics (63.5% female) included in the study, 219 (37.1%) were treated with omalizumab, 358 (60.6%) with mepolizumab, and 14 (2.4%) with benralizumab. In total, 26 patients (4.4%) had a confirmed SARS-CoV-2 infection, 9 (34.6%) of whom were admitted to the hospital because of severe COVID-19, and 1 required mechanical ventilation and died 19 days after admission. Of the 26 infected patients, 5 (19.2%) experienced asthma control deterioration, characterized as exacerbation that required treatment with systemic corticosteroids. The scheduled administration of the biological therapy was performed timely in all patients with the exception of 2, in whom it was postponed for 1 week according to their doctors' suggestion. CONCLUSION: Our study confirms that despite the initial concerns, SARS-CoV-2 infection is not more common in asthmatics treated with biologics compared with the general population, whereas the use of biologic treatments for severe asthma during the COVID-19 pandemic does not seem to be related to adverse outcomes from severe COVID-19.


Subject(s)
Asthma , Biological Products , COVID-19 , Adrenal Cortex Hormones , Asthma/drug therapy , Asthma/epidemiology , Biological Products/therapeutic use , Female , Humans , Male , Omalizumab/therapeutic use , Pandemics , SARS-CoV-2
7.
J Asthma Allergy ; 15: 623-632, 2022.
Article in English | MEDLINE | ID: covidwho-1869275

ABSTRACT

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.

8.
Biomedicines ; 9(12)2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-1785519

ABSTRACT

BACKGROUND: The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. PATIENTS AND METHODS: Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. RESULTS: In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). CONCLUSION: The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

9.
J Inflamm Res ; 14: 6845-6853, 2021.
Article in English | MEDLINE | ID: covidwho-1662469

ABSTRACT

SARS-CoV-2 pandemic had a general and deep impact on the clinical management of chronic diseases, including respiratory and allergic disorders. At the beginning of the pandemic, one of the main concerns was the potential impact of immunosuppressive/immunomodulatory drugs on COVID-19 clinical course. In this review, we aim to summarize and analyze the available clinical evidence from patients treated with anti-type 2 inflammation biologics (including anti-IgE, anti-IL-5 and anti-IL-4 agents), who developed COVID-19. Overall, the treatment with anti-Th2 biologics can be considered safe during COVID-19. It does not worsen the clinical course and outcome of COVID-19, and it may be actually protective somehow from developing severe forms. Moreover, patients treated with these biological agents do not seem to be more prone to get infected by SARS-CoV-2.

10.
Cureus ; 13(12): e20644, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1614251

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) can develop eosinopenia. Eosinophils have various functions, including immunoregulation and antiviral activity, in addition to modulation of an inflammatory reaction. Benralizumab is an anti-interleukin-5Rα monoclonal antibody that selectively depletes eosinophils through enhanced antibody-dependent cell-mediated cytotoxicity. Whether eosinophil depletion affects COVID-19 prognosis is yet to be elucidated. Here, we present a case of a 60-year-old patient with severe asthma on benralizumab therapy, who tested positive for an acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient experienced an asymptomatic COVID-19 course without deterioration of asthma control. Eosinophil depletion did not contribute to a deterioration of the clinical status. Comorbidities play a major role in the severity of COVID-19 in patients with asthma. The findings of our case and a literature review revealed that benralizumab therapy is not associated with a significant negative impact on the disease course in COVID-19 patients.

11.
Cureus ; 13(12): e20364, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1579848

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.

12.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):466, 2021.
Article in English | EMBASE | ID: covidwho-1570403

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).

13.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):468-469, 2021.
Article in English | EMBASE | ID: covidwho-1570395

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.

14.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):169-170, 2021.
Article in English | EMBASE | ID: covidwho-1570344

ABSTRACT

Background: Vasospasm due to eosinophilic coronary periarteritis (VECP) can cause not only vasospastic angina but also myocardial infarction and sudden cardiac death. It is usually resistant to conventional treatment of coronary disease and responds to systemic corticosteroids. The role that may have the monoclonal antibodies reducers eosinophils is unknown. Method: A 52-year-old female with chronic rhinosinusitis with nasal polyposis, moderate persistent bronchial asthma and Aspirinexacerbated respiratory disease(AERD), without atopy, had been treated with inhaled and intranasal fluticasone, oral montelukast and inhaled formoterol. In July 2019, she arrived at the emergency room with an acute coronary syndrome. Results: The procedures performed revealed high levels of troponin 16717ng/L(0- 47ng/L), and abnormal electrocardiogram (alteration of repolarization in II, III and aVF). Marked eosinophilia of 750cells/ mm3 was noticed. She was treated with oral vasodilators and aspirin, which due to her AERD required rapid desensitization, being effective. However, she continued with recurrent chest pain and electrocardiographic abnormalities. Diagnostic coronary angiography revealed vasospasm in the right coronary artery without atheromatous lesions. Type 2 myocardial infarction secondary to VECP was suspected and prednisone 30mg/day was started with complete resolution of chest pain. She developed a Cushing syndrome and prednisone dose was reduced, but chest pain and eosinophilia(1000/mm3) reappeared, and prednisone 20mg/day was reintroduced. It was decided to discontinue corticosteroids and treatment was begun with anti-IL-5(benralizumab) in May 2020, reducing eosinophilia( 0/mm3) from the first dose. At 6 months we suspended prednisone without new episodes of pain. In August 2020, she was visited due to SARS-CoV-2 infection without symptoms of bronchospasm or pneumonia and received the 4th dose of benralizumab without complications. Conclusion: An acute coronary syndrome refractory to conventional medications with normal coronary arteries and eosinophilia, with a history of chronic rhinosinusitis/polyposis, asthma and/or AERD, VECP should be considered and early treatment with corticosteroids could save lives. This is the first case to our knowledge in which anti IL 5 has been used for VECP to control of the eosinophilic disorder. Likewise, it was administrated during the SARS-CoV-2 infection without complications.

15.
Allergol Select ; 4: 53-68, 2020.
Article in English | MEDLINE | ID: covidwho-761024

ABSTRACT

BACKGROUND: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2. MATERIALS AND METHODS: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic. RESULTS: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future. CONCLUSION: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.

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