Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in COVID-19 patients: A systematic review

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening drug-induced condition presenting with skin rash, fever, lymphadenopathy, systemic involvement and hematological (eosinophilia, atypical lymphocytes) findings. Although DRESS syndrome is frequently associated with reactivation of herpesviruses, the link between DRESS and COVID-19 has not been systematically analyzed. Method(s): A systematic search using PubMed and Google Scholar was conducted following the PRISMA guidelines to identify all reported DRESS cases associated with COVID-19 published between January 2020 and January 2022 using the keywords "COVID-19" AND "DRESS syndrome" OR "drug reaction with eosinophilia and systemic symptoms" OR "drug-induced hypersensitivity syndrome" OR "eosinophilia" AND "SARS-CoV- 2" OR "coronavirus". The identified DRESS cases were evaluated using the Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system [Kardaun et al, 2007]. Result(s): We identified twelve published DRESS cases associated with COVID-19 (Table 1). Eleven patients presented with severe COVID-19 disease complicated by DRESS syndrome that developed several days after initial COVID-19 clinical presentation (ARDS n5;multiorgan failure n1;pneumonia requiring mechanical ventilation, n4), one patient was asymptomatic. The culprit drugs included piperacillin-tazobactam (n4), hydroxychloroquine (n5), vancomycin (n2), ceftriaxone (n1), midazolam (n1), sulphasalazine (n1), azithromycin (n1), esomeprazole (n1), cefepime (n1), levofloxacin (n1), and meropenem (n1). The latency between the onset of treatment with culprit drug(s) and the onset of symptoms ranged from 9 to 42 days. All patients presented with widespread maculopapular rash, affecting > 50% of body surface area;five patients also had facial edema. Systemic involvement included liver (n8), renal abnormalities (n8), and heart involvement (n4). All patients had elevated body temperature (fever > = 38.5degreeC, n6) and blood eosinophilia, five patients had lymphadenopathy. Atypical lymphocytes were a rare laboratory finding (n2). Systemic corticosteroids were used in all patients;three patients received benralizumab for DRESS syndrome. Nine patients recovered, two patients died and the outcome was not reported in one case Conclusion(s): DRESS syndrome in COVID-19 patients is associated with multiple drugs, most notably with hydroxychloroquine and a variety of antibiotics. An early recognition may improve management of DRESS syndrome in COVID-19 patients.

The use of biologics during the COVID 19 pandemic: Data of an allergy unit of a tertiary hospital in Greece

Background: The use of biologics during the pandemic has raised concerns throughout the scientific community. The current guidelines suggest continuing the use of biologics during the pandemic, while the initiation or continuation of treatment in case of symptomatic disease are remaining controversial unanswered questions. As a result the purpose of this study was to determine the frequency of symptomatic COVID19 infection in patients treated with biologic agents in an Allergy Unit of a University Hospital during the pandemic. Method(s): Patients of the Allergy Unit "D Kalogeromitros", who due to asthma, atopic dermatitis, Chronic Spontaneous Urticaria(CSU) or Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)were under treatment with biologic agents were included in the present study. Treatment of at least 2 months until the 31/12/2021 was necessary for a patient to be included in the present study. Result(s): A total of 77 patients [46 (59.7%) women, mean age 48.2 (range 15-82) years were included. The mean duration of treatment with biologics was 34.9 months (SD: +/-37 months). Overall, 83.1% (64/77) of patients were receiving omalizumab for asthma and CSU [13/64 (20.3%) and 51/64 (79.6%) respectively] while 9.1% (7/77) were receiving dupilumab for atopic dermatitis (4/7) and CRSwNP [4/7 (57.1%) and 3/7 (42.8%) respectively]. In addition, 5/77 (6.5%) and 1/77 (1.2%) were under treatment with mepolizumab and one with benralizumab respectively, due to severe uncontrolled asthma. A total of 6 patients with chronic spontaneous urticaria and 2/19 patients with asthma (1/5 with mepolizumab and 1/13 with omalizumab) had symptomatic COVID 19 infection as confirmed with a positive Polymerase Chain Reaction or Rapid Test. None of the patients treated with benralizumab or dupilumab had symptomatic COVID19 infection. Overall, 8/77 (10.3%) of patients had symptomatic SARS-CoV2 infection during the above period, a rate similar to the onein the same period identified in the general Greek population (11.2%). All patients had mild symptoms during the disease course with no patient admission to hospital. Conclusion(s): The frequency of symptomatic COVID19 infection identified in a population of Greek patients treated with biologic agents was no higher than than the one in the general Greek population. Furthermore, all patients had a mild course of the disease with no admissions, indicating that the use of biologics is a safe choice and can be continued during the pandemic.

Aspergillus overlap syndromes: From allergic bronchopulmonary aspergillosis to invasive pulmonary aspergillosis

Case report Background: Aspergillus is a saprophytic mold that can cause a broad variety of pulmonary syndromes, categorized in three branches: allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA) and invasive pulmonary aspergillosis (IPA). Although these three pathologies involve damaged lung tissue and presence of Aspergillus, it is uncommon to find more than one of them in the same patient. In recent years, overlap of these syndromes is being recognized in some patients, primarily in those treated with immunosuppressive agents, such as long term use of corticosteroids. Case report: We report a case of a 54 year old woman diagnosed with ABPA in 2014, that, following treatment for her pathology with steroids and benralizumab (monoclonal antibody against interleukin- 5), developed IPA, that required hospital admission and treatment with antifungal agents. Since the diagnosis of ABPA, she had been treated with oral corticosteroids and antifungal agents in 2 occasions (2014 and 2017) and omalizumab (monoclonal antibody against IgE) in 2016. Omalizumab had to be discontinued after second administration due to flu-like symptoms, headache, joint and neck pain. In February 2020 due to lack of control of her illness with 15 mg oral prednisone daily, she initiated treatment with benralizumab, being hospitalized after the onset of this new medication as a result of an asthmatic exacerbation. Due to COVID pandemic, she reinitiated benralizumab in June 2020, and continued ever since the administration at home every 2 months in association with 7.5 mg oral Prednisone daily. Following clinical worsening of the patient, a thorax CT scan was performed in September 2021, where a nodule accompanied by a "halo" sign was visualized. The patient was admitted to hospital to start new treatment with higher dose of corticosteroids, antifungal therapy, supplementary oxygen and benralizumab was discontinued. Conclusion(s): To our knowledge, this is the first case of IPA secondary to ABPA in a patient treated with a monoclonal antibody and long term oral corticosteroids. Physicians should be aware of this possible overlap syndromes so that appropriate therapy can be instituted.

A study of new drug approval pattern of a Southeast Asian developed country from 2017 to 2021

Background: The pattern of new drug approval is changing across the world as shown by the study using Center for Drug Evaluation and Research and European Medicines Agency data in US and UK with more drug approval for anti-cancer and immunomodulator drugs. There is a need to generate similar database for developed South East Asian countries too. Aims and Objectives: This study was conducted for one such country-Singapore for the new drug approval pattern of last 5 years (2017-2021). Material(s) and Method(s): This was a pharmacoepidemiological study, in which government drug regulatory website data available in public domain was searched. The new drug approval data were classified according to active ingredient, drug approval date, new drug application category, indication of drugs, and World Health Organization Anatomic Thoracic Classification. Result(s): In this study, 418 new drug approvals were found in last 5 years in Singapore. From this maximum, drug approvals were given to anti-neoplastic and immunomodulator category drugs. In anti-neoplastic category new drugs approval few examples were Trastuzumab deruxtecan and Tucatinib for breast cancer therapy and Tepotinib and Capmatinib for non-small cell lung cancer therapy. Conclusion(s): This study shows that drug development in anti-cancer drug and immunomodulator is significant in Singapore. This trend is quite matching with other country such as US and UK.Copyright © 2023 Priti Solanky, et al.

Humoral immune responses to COVID-19 vaccines are reduced in patients with severe asthma

Background: Patients with severe asthma (SA) may be at higher risk of severe COVID-19 (C-19) illness. C-19 vaccines aim to reduce number and severity of infections. Patients with SA are often treated with maintenance oral corticosteroids (mOCS) and/or biologics (mAb)- it is unknown if vaccines will generate the same protective responses in patients with SA on such therapies. Aim(s): To compare magnitude and range of post-vaccination (PV) antibody responses (IgG) in patients with SA on mAb, mOCS or high-dose inhaled corticosteroids (ICS) with healthy controls (HC) without asthma. Method(s): The Virtus finger-prick quantitative C-19 antibody test was used to detect IgG levels 16-24 weeks post second-dose of the C-19 vaccine (123 AstraZeneca, 56 Pfizer, 5 Moderna). IgG>0.2AU was considered positive with range: very high >1.25AU, high 0.751-1.25AU, medium 0.401-0.75AU and low 0.201-0.4AU. SA was defined as per ATS/ERS criteria. Result(s): PV IgG results were obtained from 127 patients with SA (84 mAb, 13 mOCS and 46 ICS) and 57 HC. After adjusting for age, significantly fewer people with SA compared to HC had a positive PV IgG result (81% vs 95% p=0.016). Lower median IgG levels were seen in patients on mOCS (0.40AU) compared to HC (1.24AU) (p=0.051). Patients on mAb had high or very high IgG levels (omalizumab n=25, 0.80AU;mepolizumab n=25, 1.07AU;benralizumab n=34, 1.11AU). Conclusion(s): Overall, a higher proportion of patients with SA had a negative PV IgG level after receiving 2 doses of a C-19 vaccine. This was mainly seen in patients on mOCS while mAb use was associated with high levels of humoral antibody response. These results reinforce the need for booster vaccines in SA, especially in those on mOCS.

Severe asthma outcomes in patients self-administering biological therapy at home

Introduction: The use of biological therapy in eosinophilic and atopic asthma has grown exponentially over the last 14years. Treatment was initially hospital-based, but the COVID-19 pandemic has accelerated the implementation of patient homecare self-administration (HSA) of biologics. Aim(s): To assess the stability of patients transfered on HSA by comparing data from biologic initiation to HSA discharge and annual review. Result(s): This report includes 56 patients who attended for annual review between April and December 2021 (60% female, mean age 54 [SD13.4]) for Benralizumab (42.9%), Mepolizumab (35.7%) and Omalizumab (21.4%). The time on biologic when commencing HSA was 19 (IQR 21.8) months, with an annual review 12 (IQR 8.3) months later. Previously obtained improvements in asthma control, lung function, eosinophil suppression and oral corticosteroid use, were maintained in 53(95%) of the patients (Table 1). HSA was stopped in 3(5%) patients due to deterioration in asthma control. Conclusion(s): The vast majority of patients recieving HSA of biologics maintained previous improvements across asthma outcomes, thereby strongly supporting the use of HSA in the correctly identified patient, consequently optimising service capacity. Appropriate monitoring arrangements are still needed to promptly identify any deterioration. (Table Presented).

Smell improvement by anti-IgE and anti-IL 5 biologics in patients with CRSwNP and severe asthma. A real life study.

BACKGROUND AND OBJECTIVE: Chronic rhinosinusitis with nasal polyps (CRSwNP), characterized by partial (hyposmia) or total (anosmia) loss of smell, is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), worsens disease severity and quality of life. Objectives. The objective of this study was to determine whether, in real-life conditions, biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare smell improvement in N-ERD and non-N-ERD subgroups. METHODS: A multicenter, non-interventional, retrospective, observational study was performed, including 206 patients with severe asthma undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab) with CRSwNP. RESULTS: Improved olfaction was found after treatment with all monoclonal antibodies: omalizumab (35.8%), mepolizumab (35.4%), reslizumab (35.7%), and benralizumab (39.1%), with no differences between groups. Patients with atopy, greater use of short course systemic corticosteroids, and larger polyp size were more likely to experience improvement in smell. The proportion of patients experiencing smell improvement was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSION: This is the first study to compare real-life improvement in sense of smell among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in sense of smell (with non-significant differences between biologic drugs). No differences were found in smell improvement between the N-ERD and non-N-ERD group.

Off-Label Benralizumab in Severe Non-Necrotizing Eosinophilic Vasculitis following Critical COVID-19 Disease and in DRESS.

Benralizumab is a humanized recombinant mAb that binds to the interleukin 5 receptor (IL-5R) expressed on eosinophils and is approved for the treatment of severe eosinophilic asthma. There are a series of severe eosinophilic disorders that may benefit from this treatment, and it could be a life-saving therapy. In this paper, we present two severe patients with eosinophil-induced diseases that had a good resolution after one dose of Benralizumab 30 mg. The first case is a severe non-necrotizing eosinophilic vasculitis following critical COVID-19 disease and the second case is a DRESS (Drug Rash with Eosinophilia and Systemic Symptoms Syndrome) due to allopurinol. Conclusions: The successful administration of Benralizumab in rare or severe eosinophilic disease could be an option for life-saving therapies when conventional treatments fail.

PATIENTS WITH ASTHMA OR ATOPIC DERMATITIS TAKING BIOLOGIC THERAPIES HAVE REDUCED SARS-COV-2 VACCINE RESPONSE AT SIX MONTHS

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

EFFECTS OF BENRALIZUMAB ON AIRWAY DYNAMICS IN SEVERE EOSINOPHILIC ASTHMA USING FUNCTIONAL RESPIRATORY IMAGING PARAMETERS: THE BURAN STUDY DESIGN

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

Severe Toxic Epidermal Necrolysis and Drug Reaction with Eosinophilia and Systemic Symptoms Overlap Syndrome Treated with Benralizumab: A Case Report

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.

Characteristics and Outcomes of Patients with Severe Eosinophilic Asthma Treated with Benralizumab Enrolled in the Connect 360 Patient Support Programme

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.

Effectiveness of Anti-IL4R Therapy Following Suboptimal Response to Anti-IL5/5R Therapy in Severe Eosinophilic Asthma

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.

SARS-Cov-2 Infection in Severe Asthma Patients Treated With Biologics.

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.

Reliability, Satisfaction and Effectiveness of Benralizumab Home Self-Administration in Patients with Severe Eosinophilic Asthma in Real-World Practice: The Auto-Benra Study.

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.

Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy.

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.

Impact of Anti-Type 2 Inflammation Biologic Therapy on COVID-19 Clinical Course and Outcome.

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.

COVID-19 in a Patient With Severe Eosinophilic Asthma on Benralizumab Therapy: A Case Report and Review of Literature.

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.

Long-Term Follow-Up of a Severe Eosinophilic Asthmatic Patient With Comorbid Nasal Polyposis Hospitalized for SARS-CoV-2 Infection While Receiving Benralizumab: A Case Report.

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.