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Background and Objective: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on‐treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on‐treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Throughout 2 years of treatment with benralizumab, a four‐component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function. Results: The present study recruited 164 patients suffering from SEA. After 24 months of add‐on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on‐treatment (exacerbation rate = 0, OCS dose = 0, pre‐bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT‐22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post‐bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on‐treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively). Conclusion: Taken together, the results of this real‐life clinical investigation indicate that benralizumab can induce a sustained remission on‐treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation. [ABSTRACT FROM AUTHOR]

Background: Benralizumab has been reported to lead to clinical remission of severe eosinophilic asthma (SEA) at 1 year in some patients. However, whether this is maintained over a longer term remains unclear. Additionally, the impact of pulmonary and extrapulmonary comorbidities on the ability to meet remission is poorly understood. Methods: Clinical outcomes including remission of SEA with benralizumab at 1 and 2 years were assessed retrospectively in a real‐world UK multi‐centre severe asthma cohort. The presence of clinically relevant pulmonary and extrapulmonary comorbidities associated with respiratory symptoms was recorded. Analyses to identify factors associated with the ability to meet remission were performed. Results: In total, 276 patients with SEA treated with benralizumab including 113 patients who had switched from a previous biologic to benralizumab were included. Overall, clinical remission was met in 17% (n = 31/186) and 32% (n = 43/133) of patients at 1 and 2 years, respectively. This increased to 28% at 1 year and 49% at 2 years once patients with pulmonary and/or extrapulmonary comorbidities were excluded. Body mass index (BMI) and maintenance OCS (mOCS) use demonstrated a negative association with clinical remission at 1 (BMI: OR: 0.89, 95% CI: 0.82–0.96, p < 0.01; mOCS: OR: 0.94, 95% CI: 0.89–0.99, p < 0.05) and 2 years (BMI: OR: 0.93, 95% CI: 0.87–0.99, p < 0.05; mOCS: OR: 0.95, 95% CI: 0.89–0.99, p < 0.05). Conclusions: In this long‐term, real‐world study, patients with SEA demonstrated the ability to meet and sustain clinical remission when treated with benralizumab. The presence of comorbidities including obesity, which are known to be independently associated with respiratory symptoms, reduced the likelihood of meeting clinical remission. [ABSTRACT FROM AUTHOR]

The aim of this retrospective multicentre study is to describe the clinical characteristics of patients diagnosed with severe eosinophilic asthma receiving anti-IL-5/anti-IL-5Rα therapies and to compare their effectiveness. We collected and analysed results separately for anti-IL-5 and anti-IL-5Rα therapies from January 2016 until December 2021 in multidisciplinary severe asthma units. We collected demographic and clinical data, treatment with previous anti-IgE and/or anti-IL-5 agents, and comorbidities. We compared the number of exacerbations and admissions to the hospital, daily oral corticosteroid intake, pulmonary function tests, and Asthma Control Test scores before and after 12 months of therapy. 261 patients were included: 176 patients in the anti-IL-5 group and 85 in the anti-IL-5Rα group. Both groups led to statistically significant reductions in asthma exacerbations, hospital admissions, and visits to the Emergency Room. Although both groups showed a significant reduction in blood eosinophiliccount, we found a difference, although not significant, in the magnitude of reduction as benralizumab was able to decrease eosinophil counts to zero. Patients in the anti-IL-5 group achieved higher ACT scores after treatment, although this improvement was seen in both treatment groups. The anti-IL-5 and anti-IL-5Rα biologics have shown similar effectiveness despite having different mechanisms of action. The anti-IL-5 group appeared to be better than benralizumab at improving ACT scores and FEV1/FVC and at reducing the number of inhalers. Although these differences were not statistically significant, it is not clear whether they may have clinical relevance and they might highlight the need for further head-to-head studies comparing these treatments. [ABSTRACT FROM AUTHOR]

ContextRecent insights into type 2 inflammation have led to the development of monoclonal antibody therapies for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Despite add-on therapy with a monoclonal antibody, some individuals remain uncontrolled in terms of upper and/or lower airway symptoms, prompting an exploration of the efficacy of combining biological therapies and their impact on inflammatory pathways.ObjectivesIn this article, we present a distinctive case of a patient with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, who experienced substantial clinical and local inflammatory improvements through dual monoclonal antibody therapy.MethodsWe provide a detailed case description and analysis of the patient's nasal tissue and secretions to gain insights into the local nasal inflammation under this unique therapeutic approach.ResultsThe addition of an anti-IL-4Rα antibody led to an improvement in upper airway symptoms and a reduction in both eosinophilic and neutrophilic inflammation, despite prior anti-IL-5 therapy. These effects were consistently observed in both polyp tissue and nasal secretions.ConclusionOur patient, with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, experienced substantial improvement with dual monoclonal antibody therapy, without major complications or side effects.

This article discusses the effects of benralizumab, a medication used to treat severe eosinophilic asthma, on basophils, a type of white blood cell. The study found that benralizumab reduced the percentage and activation of basophils in patients with severe eosinophilic asthma. The medication did not cause basophil degranulation or promote allergic reactions. Additionally, the study identified changes in the miRNA profile of basophils after benralizumab treatment. These findings suggest that benralizumab may have a dual benefit in reducing both eosinophils and basophils in patients with severe eosinophilic asthma. [Extracted from the article]

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV1) (+440 mL at 36 months, p < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab's long-term safety. [ABSTRACT FROM AUTHOR]

The prevalence of asthma in adults >65 years old is approximately 12–14%, and 10% have severe asthma. A higher mortality rate is observed in subjects with asthma >65 years old and especially >80 years old. To analyze the effectiveness and safety of at least three doses of benralizumab in a subgroup of elderly subjects (>65 years old) with uncontrolled severe eosinophilic asthma in real-life conditions. This was a retrospective multicenter study (AUTOBENRA study) conducted in 9 hospitals that included 72 patients aged >18 years old with uncontrolled severe asthma based on the Spanish Asthma Guidelines who were treated with at least three doses of benralizumab, self-administered at home since before April 30, 2021. The recruitment period ended on October 1, 2021. Written consent was obtained before the study commencement. In this subanalysis, we compared the results between patients >65 years old and patients <65 years old. A total of 72 subjects with severe asthma were screened, and 54 were included (MD: 57.3 ± 10 years old). There were 12 subjects aged >65 years old [MD: 69.8 ± 4.3 years old (minimum: 65 years old; maximum: 83 years old)]. Subjects >65 years old experienced statistically significant improvement in lung function, ACT and mini-AQLQ with benralizumab. Additionally, 9 patients (75%) experienced no asthma exacerbation (p = 0.0047), half (3/6) were able to stop OCS (p = 0.08), and no adverse effects with benralizumab were reported during the 20 months of follow-up. In patients aged >65 years old, benralizumab was an effective and safe therapy for severe eosinophilic asthma in our study, with no significant differences from the younger subgroup. This is especially important since they are a group with numerous comorbidities, medications and worse quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3–10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. Method: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. Results: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. Conclusions: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders. [ABSTRACT FROM AUTHOR]

Background and Objectives: Severe adult-onset eosinophilic asthma and COPD with eosinophilic inflammation are two entities with a similar clinical course and are sometimes difficult to differentiate in clinical practice, especially in patients with a history of smoking. Anti-IL-5 or -IL-5R biological therapy has been shown to be highly effective in severe eosinophilic asthma but has not demonstrated significant benefit in patients with COPD with the eosinophilic phenotype. Our aim was to illustrate this issue in the form of a case report. Materials and Methods: We present the case of a 67-year-old patient who is a former smoker with late-onset severe uncontrolled asthma (ACT score < 15) who experienced frequent exacerbations requiring treatment with systemic corticosteroids. The patient's lung function gradually worsened to a nadir FEV1 = 18%, despite a high dose of ICS in combination with a LABA and intermittent courses of OCS, with negative allergic skin-tests, but with high blood eosinophils level. Biological treatment with an anti-IL5R monoclonal antibody (benralizumab) was initiated, despite the difficulty in the differential diagnosis between asthma and COPD with eosinophilic inflammation. Results: The patient's evolution was favorable; clinical remission was effectively achieved with significant improvement in lung function (FEV1 > 100%), but with persistence of residual mild fixed airway obstructive dysfunction (FEV1/FVC < 0.7). The therapeutic response has been maintained to date. Conclusions: Benralizumab was shown to be very effective in a patient with late-onset severe eosinophilic asthma presenting features of chronic obstructive disease—habitual exposure to tobacco and inhaled noxious substances, and persistent airflow limitation on spirometry. [ABSTRACT FROM AUTHOR]

Background: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. Objective: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. Methods: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. Results: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37–0.79] and 1.88 [1.28–2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09–2.98]). Conclusion: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response. [ABSTRACT FROM AUTHOR]

Abstract Background The ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain. Methods ORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables. Results A total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1–Q3) follow-up duration was 19.5 (14.2–24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes. Conclusions These data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP. Trial registration NCT04648839.

Aims. Mepolizumab, a fully-humanized recombinant IgG1 kappa monoclonal antibody directed against IL-5, has shown improved asthma control and lung function in randomised controlled trials. The aim of this study was to evaluate real-world clinical experience in patients with severe eosinophilic asthma treated with mepolizumab in Slovakia. Methods. A retrospective, non-interventional study based on medical records of all adult asthma patients initiating mepolizumab between November 1, 2017 and January 31, 2019, completing 12 months of treatment. At baseline, general and clinical profile data were recorded 12 months prior to treatment. Primary and secondary endpoints described the results of mepolizumab use at 2, 6, and 12 months after the initiation and compared to baseline. Statistical testing of individual change (in each patient) in selected parameters was performed. Results. The cohort included 17 patients with particularly severe asthma at baseline, with frequent severe exacerbations (SE, median 5 [IQR 4-6]/patient/year), high blood eosinophil counts (median 0.6x109/L), frequent oral corticosteroid (OCS) dependence (82.35%), median dose 15 (IQR 7.5-20) mg/day, impaired lung function, and a spectrum of comorbidities. In a one-year follow-up, the data showed reductions in median SE (0 [IQR 0-1] patient/year, eosinophilia (median 0.175x109/L) and OCS maintenance dose (median 6.25 [IQR 2.5-20] mg/day), all statistically significant after 12 months on mepolizumab. Improved and stabilised lung functions throughout the cohort and a reduced incidence of nasal polyposis were observed. Conclusions. The results provide clinical evidence of mepolizumab efficacy in a real sample of patients with severe asthma when administered in routine care settings in Slovakia.

Background: The ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain. Methods: ORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables. Results: A total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1–Q3) follow-up duration was 19.5 (14.2–24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes. Conclusions: These data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP. Trial registration: NCT04648839. [ABSTRACT FROM AUTHOR]

shown improved asthma control and lung function in randomised controlled trials. The aim of this study was to evaluate real-world clinical experience in patients with severe eosinophilic asthma treated with mepolizumab in Slovakia. Methods. A retrospective, non-interventional study based on medical records of all adult asthma patients initiating mepolizumab between November 1, 2017 and January 31, 2019, completing 12 months of treatment. At baseline, general and clinical profile data were recorded 12 months prior to treatment. Primary and secondary endpoints described the results of mepolizumab use at 2, 6, and 12 months after the initiation and compared to baseline. Statistical testing of individual change (in each patient) in selected parameters was performed. Results. The cohort included 17 patients with particularly severe asthma at baseline, with frequent severe exacerbations (SE, median 5 [IQR 4--6]/patient/year), high blood eosinophil counts (median 0.6x109/L), frequent oral corticosteroid (OCS) dependence (82.35%), median dose 15 (IQR 7.5--20) mg/day, impaired lung function, and a spectrum of comorbidities. In a one-year follow-up, the data showed reductions in median SE (0 [IQR 0--1] patient/year, eosinophilia (median 0.175x109/L) and OCS maintenance dose (median 6.25 [IQR 2.5--20] mg/day), all statistically significant after 12 months on mepolizumab. Improved and stabilised lung functions throughout the cohort and a reduced incidence of nasal polyposis were observed. Conclusions. The results provide clinical evidence of mepolizumab efficacy in a real sample of patients with severe asthma when administered in routine care settings in Slovakia. [ABSTRACT FROM AUTHOR]

Inflammatory tissue damage plays a role in the onset, progression, and exacerbation of various chronic autoimmune and metabolic diseases such as autoimmune hepatitis. Here we present a case of autoimmune hepatitis with liver eosinophilic infiltrate in a severe eosinophilic asthma patient who failed conventional immunosuppressive treatment and showed improvement in gastrointestinal symptoms after anti-interleukin-5 receptor treatment. Our case highlights the potential role of eosinophils in initiating or worsening liver inflammation in autoimmune liver disease. The link between eosinophilic inflammation, barrier damage, and chronic autoimmune diseases should be considered in clinical practice.

Background: Recently, mepolizumab and benralizumab have been approved for the treatment of severe eosinophilic asthma. Objective: Thus, the main objective of the current study was to find out the exact efficacy and safety profile of mepolizumab and benralizumab in severe eosinophilic asthma. Methods: The relevant randomized controlled trials were searched in PubMed and clinical trials websites from inception to January 2022. All the analysis were done using RevMan5. Results: There is a significant reduction of asthma exacerbation in the mepolizumab and benralizumab group. However, there is no significant differences were observed in the FEV1 change. Overall adverse drug reactions (ADRs) such as headache and injection site reactions are found non-significant in the mepolizumab and benralizumab group, however, bronchitis, nasopharyngitis, upper respiratory tract infection (URTI), sinusitis, and serious adverse event (SAEs) were found to be significantly less. The subgroup analysis has also shown a similar kind of efficacy in the mepolizumab and benralizumab group however, safety analysis results have shown better safer profile of benralizumab as compared to mepolizumab. The sensitivity analysis results have shown non-alteration in the conclusion of the study regarding efficacy parameters however, overall adverse events, sinusitis, and nasopharyngitis results are altered after the exclusion of outliers. Conclusion: Mepolizumab and benralizumab appear to be safe and effective in treatment of severe eosinophilic asthma. However, more data is required to draw a valid conclusion, particularly with mepolizumab.

Gianenrico Senna,1,2 Maria Aliani,3 Elena Altieri,4 Pietro Bracciale,5 Luisa Brussino,6 Maria Filomena Caiaffa,7 Paolo Cameli,8 Giorgio Walter Canonica,9,10 Cristiano Caruso,11 Maria D’Amato,12 Fausto De Michele,13 Stefano Del Giacco,14 Fabiano Di Marco,15 Francesco Menzella,16 Girolamo Pelaia,17 Paola Rogliani,18,19 Micaela Romagnoli,20 Pietro Schino,21 Jan Walter Schroeder,22 Alessandra Vultaggio,23 Sara Rizzoli,24 Alessandro Zullo,24 Silvia Boarino,25 Marilena Palmisano,26 Alessandra Rossi,26 Gianfranco Vitiello,26 Stefano Centanni27 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 4Reparto di Pneumologia, P.O., Garbagnate Milanese, Italy; 5Reparto di Pneumologia, Ospedale Ostuni, Ostuni, BR, Italy; 6Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I, Torino, Italy; 7Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 8Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy; 9Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy; 10Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano, MI, Italy; 11Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 12UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 13UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 14Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 15Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 16UOC Pneumologia, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna, TV, Italy; 17Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 18Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 19Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 20UOC Pneumologia, ULSS 2 Marca Trevigiana, Treviso, Italy; 21Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti, BA, Italy; 22Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 23Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 24Medineos Observational Research - An IQVIA Company, Modena, Italy; 25Medical Evidence R&I, AstraZeneca, Milano, Italy; 26Medical Affairs R&I, AstraZeneca, Milano, Italy; 27Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, ItalyCorrespondence: Marilena Palmisano, Medical Affairs R&I, AstraZeneca, Milano, Italy, Email marilena.palmisano@astrazeneca.comPurpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients.Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population.Keywords: severe eosinophilic asthma, blood eosinophil count, benralizumab, observational, real-world evidence, real-life

Asthma is one of the 4 leading causes of death worldwide. Severe asthma is associated with poor quality of life, decreased life expectancy, and higher health resources consumption such as the use of oral corticosteroids (OCSs). This study aimed to assess the cost-effectiveness of mepolizumab as an add-on compared with the standard care of the Chilean public health system (combined inhaled corticosteroid therapy and a long-acting beta-agonist, short-acting beta-agonist, and OCS). A Markov model was adapted to represent the day-to-day of patients with severe asthma over a lifetime horizon. Deterministic and probabilistic sensitivity analyses were performed to account for the second-order uncertainty of the model. In addition, a risk subgroup analysis was conducted to evaluate the cost-effectiveness of mepolizumab across different risk populations. Mepolizumab produces more benefits than standard of care alone (1 additional quality-adjusted life-year, a decrease of OCS usage, an approximated 11 avoided exacerbations) but it cannot be considered cost-effective in the light of the Chilean threshold (incremental cost-effectiveness ratio: US dollars [USD] 105 967/quality-adjusted life-year vs USD 14 896). Despite this, cost-effectiveness increases in specific subgroups, with an incremental cost-effectiveness ratio of USD 44 819 in patients with eosinophil count ≥ 300 cell/mcL and exacerbation history of at least 4 exacerbations in the past year. Mepolizumab cannot be considered a cost-effective strategy for the Chilean health system. Nevertheless, price discount in specific subgroups improves its cost-effectiveness profile significantly and may offer opportunities for access to specific subgroups. • Severe eosinophilic asthma affects patients, their families, and the health system. Regarding treatments, studies have reported no cost-effectiveness for mepolizumab. Incremental cost-effectiveness ratio and quality-adjusted life-year reported on the literature study, the asthma population in general, were not different in subgroups. • Our study provides robust evidence in the cost-effectiveness of mepolizumab as an add-on to standard care. The model included 5 stages of asthma and death and provided a subgroup analysis. • Compared with the Chilean threshold, this treatment is not cost-effective, although the results and model used in this study can be used as a reference for other low- and middle-income countries seeking comparisons with their local standard of care. [ABSTRACT FROM AUTHOR]

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Overlapping eligibility to different biologics for severe asthma is still challenging, especially when addressing the same target. We aimed to characterize severe eosinophilic asthma patients according to their maintained or reduced response to mepolizumab over time and to explore baseline variables significantly associated with the occurrence of switching to benralizumab. We performed a multicentre retrospective observational study evaluating OCS reduction, exacerbation rate, lung function, exhaled nitric oxide levels (FeNO), Asthma control test (ACT), and blood eosinophil concentrations at baseline and before and after switching occurrence among 43 female and 25 male patients with severe asthma aged 23 to 84 years. Younger age, higher OCS daily dose and lower blood eosinophils at baseline were associated with a significantly higher risk (odds) for switching occurrence. All the patients showed an optimal response to mepolizumab, up to six months. The need for switching, according to the above-mentioned criterion, occurred for 30 out of 68 patients after a median time of 21 months (Q1–Q3: 12–24) from mepolizumab initiation. At the follow-up time-point after the switch (median time: 31 months, Q–Q3: 22–35), all the outcomes substantially improved and no cases of poor clinical response to benralizumab were detected. Although the small sample size and the retrospective design represent major limitations, to our knowledge, our study provides the first real-word focus on clinical variables potentially predicting a better response to anti IL-5r in patients fully eligible for both mepolizumab and benralizumab and suggests that in late non responder patients to mepolizumab, more robustly targeting the IL-5 axis may be effective. [ABSTRACT FROM AUTHOR]

Background and Objectives: Severe adult-onset eosinophilic asthma and COPD with eosinophilic inflammation are two entities with a similar clinical course and are sometimes difficult to differentiate in clinical practice, especially in patients with a history of smoking. Anti-IL-5 or -IL-5R biological therapy has been shown to be highly effective in severe eosinophilic asthma but has not demonstrated significant benefit in patients with COPD with the eosinophilic phenotype. Our aim was to illustrate this issue in the form of a case report. Materials and Methods: We present the case of a 67-year-old patient who is a former smoker with late-onset severe uncontrolled asthma (ACT score < 15) who experienced frequent exacerbations requiring treatment with systemic corticosteroids. The patient’s lung function gradually worsened to a nadir FEV1 = 18%, despite a high dose of ICS in combination with a LABA and intermittent courses of OCS, with negative allergic skin-tests, but with high blood eosinophils level. Biological treatment with an anti-IL5R monoclonal antibody (benralizumab) was initiated, despite the difficulty in the differential diagnosis between asthma and COPD with eosinophilic inflammation. Results: The patient’s evolution was favorable; clinical remission was effectively achieved with significant improvement in lung function (FEV1 > 100%), but with persistence of residual mild fixed airway obstructive dysfunction (FEV1/FVC < 0.7). The therapeutic response has been maintained to date. Conclusions: Benralizumab was shown to be very effective in a patient with late-onset severe eosinophilic asthma presenting features of chronic obstructive disease—habitual exposure to tobacco and inhaled noxious substances, and persistent airflow limitation on spirometry.

Inflammatory tissue damage plays a role in the onset, progression, and exacerbation of various chronic autoimmune and metabolic diseases such as autoimmune hepatitis. Here we present a case of autoimmune hepatitis with liver eosinophilic infiltrate in a severe eosinophilic asthma patient who failed conventional immunosuppressive treatment and showed improvement in gastrointestinal symptoms after anti-interleukin-5 receptor treatment. Our case highlights the potential role of eosinophils in initiating or worsening liver inflammation in autoimmune liver disease. The link between eosinophilic inflammation, barrier damage, and chronic autoimmune diseases should be considered in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Asthma, with several phenotypes and endotypes, is considered particularly suited for precision medicine. The identification of different non‐invasive biomarkers may facilitate diagnosis and treatment. Recently, Staphylococcus aureus and its enterotoxins (SE) have been found to have a role in inducing persistent type 2 airway inflammation in severe asthma, but also in such comorbidities as chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods: The aim of this retrospective study was to evaluate the prevalence of SE‐IgE sensitization in a multicentric Italian cohort of severe asthmatic patients and correlate it with demographic and clinical characteristics. Results: A total of 249 patients were included in the analysis, out of which 25.3% were staphylococcal enterotoxin B (SEB)‐IgE positive. We found a meaningful association between SEB‐IgE and female gender, a positive association was also measured between CRS and CRSwNP. No significant association was found between SEB‐IgE sensitization and atopy, the occurrence of exacerbations and corticosteroid dosages. In the SEB‐IgE‐positive patient, blood eosinophil count does not appear to be correlated with the severity of the disease. Patients with SEB‐IgE sensitization are, on average, younger and with an earlier disease onset, thus confirming the possibility to consider SEB‐IgE sensitization as an independent risk factor for developing asthma. Conclusions: Our data confirm that the search for SE in the initial screening phase of these patients is helpful to better phenotype them, may predict the evolution of comorbidities and lead to a targeted therapeutic choice; in this point of view this represents a goal of precision medicine. [ABSTRACT FROM AUTHOR]

Benralizumab is a biologic add-on treatment for severe eosinophilic asthma that can reduce the rate of asthma exacerbations, but data on the associated medical utilization are scarce. This retrospective study evaluated the economic value of benralizumab by analyzing healthcare resource utilization (HRU) and medical costs in a large patient population in the US. Insurance claims data (11/2016–6/2020) were analyzed. A pre-post design was used to compare asthma exacerbation rates, medical HRU and medical costs in the 12 months pre vs. post index (day after benralizumab initiation). Patients were aged ≥12 years, with ≥2 records of benralizumab and ≥2 asthma exacerbations pre index, and constituted non-mutually exclusive cohorts: biologic-naïve, biologic-experienced (switched from omalizumab or mepolizumab to benralizumab), or with extended follow-up (18 or 24 months). In all cohorts (mean age 51–53 years; 67–70% female; biologic-naïve, N = 1,292; biologic-experienced, N = 349; 18-month follow-up, N = 419; 24-month follow-up, N = 156), benralizumab treatment reduced the rate of asthma exacerbation by 53–68% (p <.001). In the biologic-naïve cohort, inpatient admissions decreased by 58%, emergency department visits by 54%, and outpatient visits by 58% post index (all p <.001), with similar reductions in exacerbation-related medical HRU in other cohorts. Exacerbation-related mean total medical costs decreased by 51% in the biologic-naïve cohort ($4691 pre-index, $2289 post-index), with cost differences ranging from 16% to 64% across other cohorts (prior omalizumab: $2686 to $1600; prior mepolizumab: $5990 to $5008; 18-month: $3636 to $1667; 24-month: $4014 to $1449; all p <.001). Medical HRU and cost reductions were durable, decreasing by 64% in year 1 and 66% in year 2 in the 24 month follow-up cohort. Patients treated with benralizumab with prior exacerbations experienced reductions in asthma exacerbations and exacerbation-related medical HRU and medical costs regardless of prior biologic use, with the benefits observed for up to 24 months after treatment initiation. Benralizumab is a biologic approved as an add-on treatment for severe eosinophilic asthma. Previous real-world studies and clinical trials have shown that benralizumab can reduce the rate of asthma exacerbations and systemic corticosteroid use. However, there is little information on the economic value of benralizumab in real-world patient populations. This study showed that patients with severe asthma in the United States had lower rates of asthma exacerbations after starting treatment with benralizumab. The patients also had fewer asthma exacerbation-related hospitalizations, emergency department visits, and outpatient visits as well as lower medical costs related to asthma exacerbations compared with before the treatment. These benefits were observed in patients who had never taken and those who had been previously treated with biologic therapies, and for up to 24 months after starting benralizumab treatment. These results show that the clinical value of benralizumab translates into reduced medical utilization for patients with severe asthma. [ABSTRACT FROM AUTHOR]

Ismael García-Moguel,1,2 Ana Rosado,3 Aída Gómez-Cardeñosa,4,5 Mar Gandolfo-Cano,6,7 Teresa Robledo Echarren,8 Maria del Mar Moro Moro,9 Mª del Mar Reaño Martos,10 Rafael Pineda-Pineda,11 Marcela Valverde-Monge,4,5 Cristina Martin-Arriscado Arroba,12 Javier Domínguez-Ortega13 On behalf of the AIRE Group1Department of Allergy, Hospital Universitario 12 de Octubre, Madrid, Spain; 2Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; 3Department of Allergy, Hospital Universitario Fundación Alcorcón, Madrid, Spain; 4Department of Allergy, University Hospital Fundación Jiménez Díaz, Madrid, Spain; 5Centro de investigación biomédica en enfermedades respiratorias (CIBERES), Instituto Carlos III, Madrid, Spain; 6Department of Allergy, Hospital Universitario de Fuenlabrada, Madrid, Spain; 7RETIC ARADyAL, Instituto de Salud Carlos III, Madrid, Spain; 8Department of Allergy, Hospital Clinico San Carlos (HCSC), Instituto de investigación sanitaria del Hospital Clínico San Carlos (IdSSC), Madrid, Spain; 9Department of Allergy, Complejo Hospitalario de Toledo, Toledo, Spain; 10Department of Allergy, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain; 11Department of Allergy, Hospital Universitario del Sureste, Madrid, Spain; 12Research and Science Support Unit, Instituto de investigación Biomédica del Hospital Universitario 12 de Octubre I+12, Madrid, Spain; 13Department of Allergy, La Paz University Hospital, Institute for Health Research (IdiPAZ), Madrid, SpainCorrespondence: Ismael García-Moguel, Tel +34 645852229, Email Ismaelgmoguel@gmail.comIntroduction: 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.Keywords: benralizumab, severe eosinophilic asthma, self-administration, severe asthma, eosinophilic asthma

Abstract Background Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness. Methods ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only. Results Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400–850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5–25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1–13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (− 93.3%) and to 0.06 for severe exacerbations (− 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0–10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index. Conclusions We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic disorder characterized by peripheral eosinophilia, severe eosinophilic asthma, sinusitis, transient pulmonary infiltrates, and features of medium/small-vessel vasculitis. EGPA belongs to the group of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides, although only 30 to 40% of patients display ANCA positivity, which is mainly of myeloperoxidase (MPO) specificity. Particularly, ANCA-positive patients typically show vasculitic features. Interleukin (IL)-5 has been demonstrated to play a crucial role in determining eosinophilic airway inflammation in EGPA patients. Specifically, maturation, activation, and survival of eosinophils especially depend on IL-5 availability. Therefore, blocking IL-5 biological activity may be a rewarding strategy for control of eosinophilic inflammation. Several monoclonal antibodies with the ability to interfere with the biological activity of IL-5 have been developed, namely, mepolizumab, reslizumab, and benralizumab. Here, we discuss the role of these drugs in the management of severe eosinophilic asthma in the context of EGPA and report the outcome of two EGPA patients with severe eosinophilic asthma treated at our outpatient clinic. [ABSTRACT FROM AUTHOR]

Purpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients. Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected. Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered. Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population. [ABSTRACT FROM AUTHOR]

Severe eosinophilic asthma (SEA) is associated with poor disease control and compromised health-related quality of life (HRQoL), leading to a substantial psychosocial and economic disease burden. Benralizumab, an interleukin-5-alpha receptor monoclonal antibody, is approved as an add-on maintenance treatment for SEA, yet real-world evidence of its effectiveness is limited. EMPOWAIR is a non-interventional, multicenter, 48-week prospective cohort study aiming to evaluate the clinical effectiveness and the patient-perceived impact of benralizumab on HRQoL, sleep quality, depression, anxiety, work productivity and activity impairment among SEA patients treated in routine care settings in Greece. The study will also engage advanced remote patient monitoring technologies using portable spirometers and wearable activity trackers to collect data on lung function parameters and physical activity. The study plans to consecutively enroll 150 adult patients treated by lung specialists practicing in various healthcare settings across the country over an 18-month recruitment period. Eligible patients must be newly prescribed benralizumab per the approved label. Primary data will be collected at enrollment and 4, 8, 16, 32, and 48 weeks after treatment initiation through routine clinic visits or telephone contacts as per the standard clinical practice. The primary objective is to assess the change from baseline in HRQoL, as measured by the St. George's Respiratory Questionnaire (SGRQ), and to estimate the proportion of patients achieving a minimum clinically important improvement in respiratory health status, defined as ≥ 4-point reduction from baseline in SGRQ total score, after 16 weeks of benralizumab treatment. The study rationale, design and protocol, are described herein. [ABSTRACT FROM AUTHOR]

Context: Recent insights into type 2 inflammation have led to the development of monoclonal antibody therapies for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Despite add-on therapy with a monoclonal antibody, some individuals remain uncontrolled in terms of upper and/or lower airway symptoms, prompting an exploration of the efficacy of combining biological therapies and their impact on inflammatory pathways., Objectives: In this article, we present a distinctive case of a patient with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, who experienced substantial clinical and local inflammatory improvements through dual monoclonal antibody therapy., Methods: We provide a detailed case description and analysis of the patient's nasal tissue and secretions to gain insights into the local nasal inflammation under this unique therapeutic approach., Results: The addition of an anti-IL-4Rα antibody led to an improvement in upper airway symptoms and a reduction in both eosinophilic and neutrophilic inflammation, despite prior anti-IL-5 therapy. These effects were consistently observed in both polyp tissue and nasal secretions., Conclusion: Our patient, with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, experienced substantial improvement with dual monoclonal antibody therapy, without major complications or side effects., Competing Interests: GB has received fees for advisory boards and/or speaker fees from Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Sanofi, and Teva Pharmaceuticals. BNL received research support from GSK and Sanofi. PG has served as an advisor or speaker and received grant/research support from ALK, GSK, Lilly, Novartis, Regeneron, Roche, Sanofi, and Stallergenes-Greer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Blauwblomme, Gevaert, Van Nevel, Riemann, Vandewalle, Holtappels, De Ruyck, Derycke, Eeckels, Vanhee, Lambrecht, Brusselle and Van Zele.)

Background: Monoclonal antibody therapy is currently an additional treatment option to reduce exacerbations and improve symptom control in patients with severe eosinophilic asthma (SEA) that is uncontrolled despite treatment with high-dose inhaled corticosteroids and long-acting beta-2 agonists. Benralizumab, a monoclonal antibody that binds to the interleukin-5 receptor (IL-5), significantly reduces symptoms and annual exacerbations, as well as the use of systemic corticosteroids in patients with SEA. However, few studies are available on the effectiveness of this biological treatment in real life. The aim of this case series was to evaluate the efficacy of benralizumab by analyzing changes in clinical parameters and blood eosinophils in patients with SEA.

BackgroundSevere asthma is a heterogeneous inflammatory disease driven by eosinophilic inflammation in the majority of cases. Despite biologic therapy patients may still be sub-optimally controlled, and the choice of the best biologic is a matter of debate. Indeed, switching between biologics is common, but no official guidelines are available and real-world data are limited.Materials and methodsIn this post hoc analysis of the Italian, multi-center, observational, retrospective study, ANANKE. Patients with severe eosinophilic asthma treated with benralizumab were divided in two groups based on history of previous biologic therapy (biologic-experienced [suboptimal response] vs naïve). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment. Change over time in blood eosinophils, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use following benralizumab initiation were collected in the two groups.ResultsA total of 147 biologic-naïve and 58 biologic-experienced (34 omalizumab, 19 mepolizumab, and 5 omalizumab-mepolizumab) patients were enrolled. Biologic-experienced patients were more likely to be atopic and have a higher AER despite more frequent OCS use. Similar reductions in AER (>90% in both groups), OCS use (≥49% reduction in dosage and ≥41% able to eliminate OCS), ACT improvement (≥7 points gained in 48 weeks) and lung function (≥300 mL of FEV1 improvement in 48 weeks) were observed after benralizumab introduction within the two groups. There were no registered discontinuations of benralizumab for safety reasons.ConclusionIn this post hoc analysis, patients who were switched to benralizumab because of suboptimal control with a previous biologic therapy were more likely to be atopic and more often treated with omalizumab. Benralizumab is effective in both naïve patients and those previously treated with a biologic.

Moritz Z Kayser,1 Nora Drick,1 Katrin Milger,2,3 Jan Fuge,1,4 Nikolaus Kneidinger,2,3 Stephanie Korn,5 Roland Buhl,6 Jürgen Behr,2,3 Tobias Welte,1,4 Hendrik Suhling1 1Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 2Department of Medicine V, University Hospital, LMU, Munich, Germany; 3Comprehensive Pneumology Center-Munich (CPC‐M), Member of the German Center for Lung Research (DZL), Munich, Germany; 4Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany; 5Clinical Research Centre for Respiratory Medicine, Mainz, Germany; 6Pulmonary Department, Mainz University Hospital, Mainz, GermanyCorrespondence: Moritz Z KayserDepartment of Respiratory Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Lower Saxony, GermanyTel +49 0511-532-3531Fax +49 511-532-161108Email kayser.moritz@mh-hannover.dePurpose: Treatment of severe eosinophilic asthma (SEA) has been revolutionized by the development of monoclonal antibodies targeting underlying immunological pathways of eosinophilic asthma. Two of the most frequently used antibodies in clinical practice are mepolizumab, targeting interleukin (IL) 5 and benralizumab, targeting the IL5 receptor alpha. The comparative treatment efficacy of these antibodies remains unclear, particularly regarding long-term outcomes.Patients and Methods: In this multicenter, retrospective study, we included 123 patients treated with mepolizumab and 64 patients treated with benralizumab for 12 months at one of three study sites in Germany. Data were collected at baseline and after 6 and 12 months of therapy. Endpoints were changes in pulmonary function (PF), exacerbation rate, oral corticosteroid (OCS) use and dose, asthma control test (ACT) score and fractional exhaled nitric oxide (FeNO) levels.Results: Both mepolizumab and benralizumab led to significant improvements in PF with an increase in median forced expiratory volume (FEV1) after 12 months from 59% to 74% for mepolizumab and 63% to 72% for benralizumab. Treatment also led to significant improvements in ACT scores after 12 months (mepolizumab: 13 [interquartile range (IQR) 9– 17] to 19 [IQR 15– 23]; benralizumab: 12 [IQR 9– 16] to 22 [IQR 16– 25]) as well as a reduction of mean OCS dose (mepolizumab 8 mg [IQR 5– 12.5 mg] median prednisolone equivalent at baseline to 5 mg [IQR 3– 7.5 mg]; benralizumab 7.5 mg [IQR 5– 15 mg] to 5 mg [IQR 2– 10 mg]). The exacerbation rates were reduced significantly, irrespective of the treatment. Overall, changes were similar after 6 and 12 months of therapy.Conclusion: Both mepolizumab and benralizumab are highly effective in the long-term treatment of SEA, with no clinically relevant differences in outcomes after 12 months of therapy. In both groups, improvements were similar after 6 and 12 months of therapy, underlining the feasibility of early treatment evaluation.Keywords: severe eosinophilic asthma, asthma control, lung, treatment response, interleukin-5, interleukin-5-receptor

Abstract Background Comorbidities can complicate the management of severe asthma; therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities. Methods This was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA. Patients aged ≥ 12 years with severe eosinophilic asthma were randomized to: mepolizumab 750, 250, or 75 mg intravenously or placebo (DREAM); mepolizumab 75 mg intravenously or 100 mg subcutaneously or placebo (MENSA); or mepolizumab 100 mg subcutaneously or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA or 52 weeks in DREAM. In this analysis the primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints were Asthma Control Questionnaire-5 score, St George’s Respiratory Questionnaire total score, and pre-bronchodilator forced expiratory volume in 1 s at study end. Subgroups were based on comorbidities at baseline. Results Overall, 1878 patients received placebo (n = 689) or mepolizumab (n = 1189). Across all comorbidity subgroups mepolizumab reduced the rate of clinically significant exacerbations by 44–68% versus placebo, improved Asthma Control Questionnaire-5 score by 0.27–0.59 points, and improved St George’s Respiratory Questionnaire total score by 5.0–11.6 points. Pre-bronchodilator forced expiratory volume in 1 s was improved by 27.1–286.9 mL in all but one comorbidity subgroup, the diabetes mellitus subgroup. Conclusions Mepolizumab reduces exacerbations, and improves asthma control, health-related quality of life, and lung function in patients with severe eosinophilic asthma despite comorbid conditions, including upper respiratory conditions, psychopathologies, cardiovascular conditions, gastroesophageal reflux disease, diabetes mellitus, and obesity. Trial registration: https://clinicaltrials.gov/ DREAM, MEA112997/NCT01000506; MENSA, MEA115588/NCT01691521; SIRIUS, MEA115575/NCT01842607; MUSCA, 200862/NCT02281318.

Abstract Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, small vessel, necrotizing vasculitis. The disease is mainly characterized by hypereosinophilia and asthma with frequent sinonasal involvement, although multiple organs can be affected, including the heart, lungs, skin, gastrointestinal tract, kidneys, and nervous system. IL-5 production is pathogenetically central for the development of the disease by promoting proliferation, transvascular migration and functional activation of eosinophils. The degree of blood and tissue eosinophilia appears to be associated with disease pathogenesis and eosinophil depletion represents a promising treatment approach for EGPA. We prospectively evaluated the efficacy and safety of a low dose (100 mg q4w), 12-month course of mepolizumab, an anti-IL-5 monoclonal antibody, in eight patients with severe asthma and active EGPA. Patients were recruited by the tertiary care center of Clinical Immunology and Allergy, University of Naples Federico II. The following outcomes were assessed before (T0), and after 6 (T6) and 12 months (T12) of mepolizumab treatment: Birmingham Vasculitis Activity Score (BVAS), prednisone intake, Sino-Nasal Outcome Test (SNOT-22), Total Endoscopic Polyp Score (TENPS), Asthma Control Test (ACT), Forced Expiratory Volume one second (FEV1)%, blood eosinophilia. BVAS score significantly decreased showing a sharp reduction in disease activity score. Clinical improvements in terms of sinonasal scores and asthma symptoms were observed, in parallel with a drastic drop in eosinophil blood count. Prednisone intake was significantly reduced. In two patients, asthma exacerbations led to discontinuation in mepolizumab therapy after 6 and 12 months despite BVAS reduction. Mepolizumab treatment was well tolerated, and no severe adverse drug effects were registered. In conclusion, our 12-month real-life study suggests that mepolizumab may be beneficial and safe in active EGPA patients by improving disease activity score, sinonasal and asthma outcomes while reducing the burden of prednisone intake.

Interleukin (IL)-5 plays an important role in development, recruitment, and survival of eosinophils, thereby causing debilitating signs and symptoms associated with severe eosinophilic asthma. Mepolizumab is a humanized monoclonal antibody (mAb) against IL-5 which selectively inhibits eosinophilic inflammation and reduces the amount of eosinophils. This reduction is seen in both sputum and blood, resulting in a reduction in exacerbations and in time the need for using systemic steroids. The role of mepolizumab and its effect is still not fully known as there are less real-life studies available. We herewith present a case of severe eosinophilic asthma with vocal polyp managed by mepolizumab.

Background: Currently, disease control in patients with severe eosinophilic asthma is not optimistic. Competing endogenous RNA (ceRNA) networks have been found to play a key role in asthma in recent years. However, it is unclear whether ceRNA networks play an important part in severe eosinophilic asthma. Methods: Firstly, gene expression profiles related to severe eosinophilic asthma were downloaded from the Gene Expression Omnibus (GEO) database. Secondly, the key modules were identified by the weighted gene co-expression network analysis (WGCNA). Thirdly, genes in modules highly associated with severe eosinophilic asthma were selected for further construction of the ceRNA network. Fourthly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on hub genes. Finally, the results of this study were validated on the GSE143303, GSE137268, and GSE147878 datasets. Results: 22 severe eosinophilic asthmatics and 13 healthy controls were extracted for WGCNA. We found that the genes in the black module (r = −0.75, p < 0.05) and yellow module (r = 0.65, p < 0.05) were highly associated with severe eosinophilic asthma. EP300 was discovered to serve the key connecting function in the ceRNA network. Surprisingly, lncRNAs seem to eliminate the role of EP300 in the black module and we discovered that CCT8 and miRNA-mRNA formed a circRNA-miRNA-mRNA network in the yellow module. We found that EP300 and FOXO3 in the black module were regulated by steroid hormones in the enrichment analysis, which were related to the medication used by the patient. Through validation of other datasets, we found that the hub genes in the yellow module were the key genes in the treatment of severe eosinophilic asthma. In particular, RPL17 and HNRNPK might specifically regulate severe eosinophilic asthma. Conclusion: RPL17 and HNRNPK might particularly regulate severe eosinophilic asthma. Our results could be useful to provide potential immunotherapy targets and prognostic markers for severe eosinophilic asthma. [ABSTRACT FROM AUTHOR]

Background: Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups. Objectives: We aimed to describe the characteristics of SEA and identify its patient subgroups. Methods: Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts. Results: Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (n = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/μL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (n = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/μL). Lastly, cluster 3 (n = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/μL), and good treatment response in terms of improved lung function and control status. Conclusions: Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab has been approved as a treatment option for severe eosinophilic asthma (SEA) patients in our country. We aimed to evaluate the clinical and functional efficacy of mepolizumab in this group of patients in real life as well as the response rates to mepolizumab and the possible factors affecting the response. Methods: The study was a retrospective chart review of patients with SEA treated with mepolizumab. The data were collected at baseline, and at the 6th and 12th month. Results: A total of 62 patients (41F/21M) with a mean age of 44.41 ± 13.24 years were included in the study. They had poor symptom control with a mean asthma control test (ACT) score of 16.61 ± 5.59, frequent exacerbations with a mean of 3.4 ± 3.7 in the previous 12 months, and 80.6% required daily oral corticosteroid (OCS) with a median dosage of 8 mg/day as methylprednisolone. The ACT score increased to 22.47 ± 3.18 and 22.03 ± 4.31, respectively, and blood eosinophil count decreased from 1,146/μL to 89/μL and 85/μL at the 6th and 12th month, respectively. The mean FEV1 at baseline was 2.102 L there was an increase of 0.373 L at 6th month and 0.596 L at 12th month. The percentage of regular users of OCS decreased to 66.0% at 6th month with a median dosage of 4 mg and 52.6% at 12th month with a median dosage of 2 mg. Mepolizumab reduced the rate of exacerbations compared with the previous year from a mean of 3.40 to 0.15 at 6th month and 0.36 at 12th month. There was a significant improvement in Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Sino-nasal Outcome Test (SNOT-22) scores at both of time points. The rate of responders and super-responders at 6th month was 60% and 28%, respectively, and consequently, the overall response rate was 88%. At the 12th month, the super-responder rate increased to 44.7% as well as the overall response to 89.4%. The only difference between the nonresponders, responders, and super-responders at the 6th and 12th month was whether regular daily OCS was used pre-mepolizumab. All nonresponders at both 6th and 12th month were using OCS regularly, whereas most of super-responder used the OCS only during exacerbations. Conclusion: Mepolizumab effectively reduced asthma exacerbations, steroid requirement, blood eosinophil counts and improved asthma control, pulmonary function, sinonasal symptoms and quality of life. Our data suggest that mepolizumab would be effective in selected patients in real-life settings. [ABSTRACT FROM AUTHOR]

Introduction: Consensus definitions for clinical remission and super-response were recently established for severe asthma. Benralizumab is an interleukin-5 (IL-5) receptor α-directed monoclonal antibody for severe, uncontrolled asthma; efficacy and safety were demonstrated in previous pivotal phase 3 trials (SIROCCO, CALIMA, ZONDA). This analysis applied a composite remission definition to characterize individual responses to benralizumab after 6 and 12 months. Methods: In previous phase 3 studies, eligible patients were those with severe, uncontrolled asthma receiving medium- or high-dosage inhaled corticosteroids plus long-acting β2-agonists. This post hoc analysis included patients randomized to the approved benralizumab dose and not receiving oral corticosteroids (OCS) at baseline (SIROCCO/CALIMA) or OCS ≤ 12.5 mg per day (ZONDA). Individual remission components were zero exacerbations; zero OCS use; Asthma Control Questionnaire-6 (ACQ-6) score < 1.5 or ≤ 0.75; and pre-bronchodilator forced expiratory volume in 1 s (FEV1) increase ≥ 100 mL; clinical remission incorporated zero exacerbations, zero OCS use, ACQ-6 score ≤ 0.75, and pre-bronchodilator FEV1 increase ≥ 100 mL after 6 or 12 months. Results: Overall, 609 patients (N = 301 and N = 308) and 586 patients (N = 293 and N = 293) receiving benralizumab in SIROCCO and CALIMA were included at 6 and 12 months, respectively; 40 ZONDA patients were included after 6 months. In SIROCCO/CALIMA, similar to 6-month findings, approx. 83% and approx. 49% receiving benralizumab, and 77% and 37% on placebo achieved ≥ 2 and ≥ 3 remission components after 12 months; 14.5% (85/586) on benralizumab and 7.7% (48/620) on placebo achieved clinical remission at 12 months. Among ZONDA patients, 75% and approx. 48% on benralizumab and 35% and 20% on placebo achieved ≥ 2 and ≥ 3 remission components at 6 months, respectively; 22.5% (9/40) on benralizumab and 7.5% on placebo achieved clinical remission. Conclusions: This analysis demonstrates clinical remission is achievable by targeting the underlying drivers of inflammation. Precision medicines can help shift treatment paradigms toward treat-to-target, with clinical remission as the ultimate therapeutic goal in severe asthma. Clinical trial registration: SIROCCO (NCT01928771); CALIMA (NCT01914757); ZONDA (NCT02075255). Plain Language Summary: Widely accepted definitions for disease remission are already established for the treatment of rheumatoid arthritis, ulcerative colitis, and cancer, among others. Two separate expert groups recently collaborated to discuss clinical remission/super-response to treatment in patients with severe asthma. Both groups developed separate, yet similar ways to determine whether a patient should be considered "in remission." In this study, we used the results from three previous trials (SIROCCO, CALIMA, and ZONDA) that were conducted to assess a therapy called benralizumab in patients with severe asthma to identify patients who met some or all of the criteria for disease remission in severe asthma. These criteria included zero asthma exacerbations; zero oral steroid (OCS) use; asthma control score; and improvement in lung function. Across all three trials, about three quarters of the patients achieved two or more remission components and about half achieved three or more remission components after 6 months of treatment; furthermore, these rates were generally similar to the numbers of patients who achieved two or more components and three or more components of remission after 12 months of treatment. Overall, 15–23% of patients achieved clinical remission in 6 months, and approximately 15% achieved remission within 12 months. The results show that biologic therapies like benralizumab help improve the symptoms of severe asthma and allow patients to achieve disease remission. [ABSTRACT FROM AUTHOR]

Severe eosinophilic asthma is characterized by chronic airway inflammation, oxidative stress, and elevated proinflammatory cytokines, especially IL-5. Mepolizumab and benralizumab are both humanized IgG antibodies directed against IL-5 signaling, directly acting on eosinophils count. Together with the complexity of severe asthma classification and patient selection for the targeted treatment, there is also the urgency to clarify the follow-up of therapy to identify biomarkers, in addition to eosinophils, for the optimal duration of treatment, persistence of effectiveness, and safety. To this purpose, here we performed a follow-up study using differential proteomic analysis on serum samples after 1 and 6 months of both therapies and sera from healthy patients. Statistical analysis by PCA and heatmap analyses were performed, and identified proteins were used for enrichment analysis by MetaCore software. The analysis highlighted 82 differences among all considered conditions. In particular, 30 referred to benralizumab time point (T0, T1B, T6B) and 24 to mepolizumab time point (T0, T1M, T6M) analyses. t-SNE and heatmap analyses evidence that the differential serum protein profile at 6 months of both treatments is more similar to that of the healthy subjects. Among the identified proteins, APOAI, APOC-II, and APOC-III are upregulated principally after 6 months of benralizumab treatment, plasminogen is upregulated after 6 months of both treatments and ceruloplasmin, upregulated already after 1 month of benralizumab, becoming higher after 6 months of mepolizumab. Using enrichment analysis, identified proteins were related to lipid metabolism and transport, blood coagulation, and ECM remodeling. [ABSTRACT FROM AUTHOR]

Corrado Pelaia,1 Claudia Crimi,2 Alida Benfante,3 Maria Filomena Caiaffa,4 Cecilia Calabrese,5 Giovanna Elisiana Carpagnano,6 Domenico Ciotta Jnr,7 Maria D’Amato,8 Luigi Macchia,9 Santi Nolasco,2 Girolamo Pelaia,1 Simona Pellegrino,7 Nicola Scichilone,3 Giulia Scioscia,10 Giuseppe Spadaro,11 Giuseppe Valenti,12 Alessandro Vatrella,7 Nunzio Crimi2 1Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy; 2Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; 3Department of Biomedicine and Internal and Specialistic Medicine, University of Palermo, Palermo, Italy; 4Allergology and Clinical Immunology Unit, University of Foggia, Foggia, Italy; 5Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Foggia, Italy; 6Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of Respiratory Disease, University “Aldo Moro” of Bari, Bari, Italy; 7Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy; 8Division of Pneumology, “V. Monaldi” University Hospital, Naples, Italy; 9Allergology and Clinical Immunology Unit, University “Aldo Moro” of Bari, Bari, Italy; 10Department of Medical and Surgical Sciences, Institute of Respiratory Diseases, University of Foggia, Foggia, Italy; 11Allergology and Immunology Unit, University “Federico II” of Naples, Naples, Italy; 12Allergology and Pulmonology Unit, Provincial Outpatient Center of Palermo, Palermo, ItalyCorrespondence: Corrado PelaiaDepartment of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, ItalyTel + 39 0961 3647007Email pelaia.corrado@gmail.comBackground: Benralizumab can be utilized as add-on biological treatment of severe eosinophilic asthma. However, so far only a few real-life studies have been published with regard to the use of this anti-IL-5 receptor humanized monoclonal antibody.Objective: The primary aim of this multicenter observational investigation has been to assess the therapeutic effects of benralizumab in patients with severe uncontrolled, corticosteroid refractory eosinophilic asthma. The secondary objective was to evaluate the efficacy of benralizumab with regard to positive or negative skin prick test (SPT).Methods: Clinical, functional, and laboratory parameters were evaluated in order to verify the therapeutic actions of benralizumab in atopic and non atopic subjects with difficult-to-treat eosinophilic asthma. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity.Results: After 6 months of add-on biological therapy with benralizumab, our 111 patients experienced a marked improvement of their severe eosinophilic asthma, expressed by significant changes in asthma exacerbation rate, prednisone intake, daily use of short-acting β2-adrenergic agonists (SABA), asthma control test (ACT) score, asthma quality of life questionnaire (AQLQ) score (56 patients), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), blood eosinophil count, blood basophil count (59 patients), and fractional exhaled nitric oxide (FeNO) levels (39 patients). In addition, significantly more effective outcomes were detected in patients with positive SPT, when compared to subjects with negative SPT, only in regard to asthma exacerbation number, ACT score, and daily SABA utilization. No significant correlation was found between serum IgE concentrations and each of all measured parameters.Conclusion and Clinical Relevance: Taken together, the results of this real-world study indicate that in both allergic and non-allergic subjects benralizumab can be used as a valuable pharmacotherapeutic option for add-on biological therapy of severe eosinophilic asthma, regardless of SPT positivity or negativity.Keywords: severe eosinophilic asthma, allergic and non-allergic phenotypes, asthma exacerbations, IL-5 receptor, benralizumab

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncontrolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improvement in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA. Case presentation A 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admitted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl. Conclusions The rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emergency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benralizumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation.

Background: Currently, disease control in patients with severe eosinophilic asthma is not optimistic. Competing endogenous RNA (ceRNA) networks have been found to play a key role in asthma in recent years. However, it is unclear whether ceRNA networks play an important part in severe eosinophilic asthma.Methods: Firstly, gene expression profiles related to severe eosinophilic asthma were downloaded from the Gene Expression Omnibus (GEO) database. Secondly, the key modules were identified by the weighted gene co-expression network analysis (WGCNA). Thirdly, genes in modules highly associated with severe eosinophilic asthma were selected for further construction of the ceRNA network. Fourthly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on hub genes. Finally, the results of this study were validated on the GSE143303, GSE137268, and GSE147878 datasets.Results: 22 severe eosinophilic asthmatics and 13 healthy controls were extracted for WGCNA. We found that the genes in the black module (r = −0.75, p < 0.05) and yellow module (r = 0.65, p < 0.05) were highly associated with severe eosinophilic asthma. EP300 was discovered to serve the key connecting function in the ceRNA network. Surprisingly, lncRNAs seem to eliminate the role of EP300 in the black module and we discovered that CCT8 and miRNA-mRNA formed a circRNA-miRNA-mRNA network in the yellow module. We found that EP300 and FOXO3 in the black module were regulated by steroid hormones in the enrichment analysis, which were related to the medication used by the patient. Through validation of other datasets, we found that the hub genes in the yellow module were the key genes in the treatment of severe eosinophilic asthma. In particular, RPL17 and HNRNPK might specifically regulate severe eosinophilic asthma.Conclusion: RPL17 and HNRNPK might particularly regulate severe eosinophilic asthma. Our results could be useful to provide potential immunotherapy targets and prognostic markers for severe eosinophilic asthma.

BackgroundSevere eosinophilic asthma (SEA) in the presence of chronic rhinosinusitis with nasal polyps (CRSwNP) indicates the presence of a more extensive eosinophilic inflammation. Post-hoc analyses from a pivotal clinical trial have demonstrated the enhanced efficacy of benralizumab on asthma outcomes in patients with CRSwNP as a comorbidity.MethodsThis is a post-hoc analysis from the Italian multi-center observational retrospective ANANKE study. Patients were divided into two groups based on self-reported CRSwNP. Baseline clinical and laboratory features in the 12 months prior to benralizumab prescription were collected. Data of change over time of blood eosinophils, annualized exacerbations rates (AER), asthma control, lung function, oral corticosteroids (OCS) use, and benralizumab discontinuation were collected during the observation period.ResultsAt baseline, the 110 patients with CRSwNP were less frequently female (50.9% vs 74.2%) and obese (9.1% vs. 22.6%) with higher eosinophils (605 vs. 500 cells/mm3) and OCS use when compared to patients without CRSwNP. Similar reductions of AER were seen (-95.8% vs. −91.5% for any exacerbation and −99.1% vs. −92.2% for severe exacerbations in patients with and without CRSwNP, respectively). During benralizumab treatment, comorbid SEA+CRSwNP was associated with a lower risk of any exacerbation (p = 0.0017) and severe exacerbations (p = 0.025). After a mean ± SD exposure of 10.3 ± 5.0 months, half of the SEA+CRSwNP patients eliminated OCS use. No discontinuation for safety reasons was recorded.ConclusionsThis study helped to confirm the baseline clinical features that distinguish patients with and without CRSwNP being prescribed benralizumab. Numerically enhanced OCS reduction and lower exacerbation risk were observed in patients with SEA and comorbid CRSwNP treated with benralizumab.

Background: Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness.Methods: ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only.Results: Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400-850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5-25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1-13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (- 93.3%) and to 0.06 for severe exacerbations (- 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0-10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index.Conclusions: We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463. [ABSTRACT FROM AUTHOR]

The article provides data on the epidemiology of severe asthma. It defines the phenotype and endotype of bronchial asthma and classifies BA according to phenotype/endotype. The features of the eosinophilic phenotype of severe bronchial asthma are considered. Clinical characteristics of the patient corresponding to the prescription of benralizumab are presented. The algorithm of decision making by a doctor-therapist about patients’ referral to a pulmonologist for consideration of the biological therapy issue is given. The results of the main clinical studies to assess the efficacy and safety of benralizumab in patients with severe eosinophilic bronchial asthma: SIROCCO, CALIMA, ZONDA, BORA are described. The experience of using various biological preparations for the treatment of severe asthma in Chelyabinsk and the Chelyabinsk Region has also been summarized.

Severe eosinophilic asthma is associated with a high corticosteroid burden, particularly in patients with comorbid chronic sinusitis/nasal polyps. This case study reports a 33-year-old woman who presented to the severe asthma center with uncontrolled severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Despite maximized asthma treatment, including maintenance oral corticosteroids (OCS) for 7 years, the patient experienced one to two hospitalizations per year, had daily symptoms that substantially impacted her quality of life, and elevated type 2 inflammatory markers (blood eosinophils, 0.72 × 109/L; fractional exhaled nitric oxide, 134 to 300 parts per billion). Her asthma worsened during her first pregnancy, in which she required five hospital admissions despite treatment with maintenance OCS. Mepolizumab treatment was commenced after pregnancy but showed limited efficacy (blood eosinophil levels up to 0.94 × 109/L); treatment was discontinued because of a second pregnancy. The patient's asthma worsened and resulted in four hospitalizations and an increase in monthly OCS dose. Mepolizumab was recommenced after pregnancy, but her asthma remained uncontrolled, symptoms persisted, and one hospitalization and nine OCS courses were required. The patient was switched to benralizumab treatment when it became available. Although her CRSwNP symptoms remained, benralizumab treatment resulted in a marked improvement in asthma control, zero hospitalizations, and suppressed blood eosinophil levels. Notably, the patient was successfully weaned off maintenance OCS after >11 years of treatment. In summary, these findings support the use of benralizumab as a corticosteroid-sparing treatment option in difficult-to-treat severe eosinophilic asthma refractory to mepolizumab treatment.

Asthma is a heterogeneous chronic disease of airways. One of its endotypes is eosinophilic asthma, accompanied by both peripheral blood and airway eosinophilia, where severe eosinophilia is usually associated with more severe asthma. Anti - interleukin-5 (IL-5) monoclonal antibodies (MAb) can reduce eosinophil counts in peripheral blood and tissues in asthma patients. The first drug of this class registered in Russia was reslizumab. Aim. Comparative clinical and economic analysis of reslizumab use in patients with allergic asthma and eosinophilia. Materials and methods. Omalizumab was chosen as a reference drug, because until now it was the only MAb for the treatment of severe asthma in Russia. The study population included patients with allergic asthma with both high levels of IgE and high eosinophil counts in peripheral blood, i.e. individuals eligible for both omalizumab and reslizumab treatment. A decrease in the number of exacerbations requiring prescription of systemic corticosteroids and an increase in QALY index was used as efficacy criteria. An indirect comparative study was used, because no direct comparison has been conducted to date. As a result, reslizumab demonstrated a statistically significant reduction in the frequency of clinically significant asthma exacerbations compared with omalizumab. The utility of the both asthma treatment strategies was compared using Markov models, taking into account the frequency of exacerbations, their severity, as well as decrease in QALYs due to exacerbations. The time horizon was 12 months. Results. Reslizumab treatment was 37.2% less expensive compared with omalizumab for the patients who are equally eligible for the both drugs. The calculated cost - effectiveness and cost - utility ratios were in favor of reslizumab. Budget impact analysis showed a significant effect of reslizumab on reducing budget costs. If reslizumab is used in 4250 patients (an estimated number of patients with severe allergic asthma and eosinophilia in Russia), this would reduce the costs for their treatment by up to 4896 million rubles per year. Conclusions. For patients with severe allergic eosinophilic asthma who are equally eligible for the both drugs, reslizumab can be considered a more reasonable medical technology in terms of pharmacoeconomics when compared with omalizumab.

Background: Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. Although mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission., Objective: To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months., Methods: The REMIssion in Severe Eosinophilic Asthma Treated with Mepolizumab (REMI-M) is a retrospective, real-world, multicenter study that analyzed 303 patients with severe eosinophilic asthma who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroid (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period., Results: Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% and 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastroesophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent., Conclusions: This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)