Cluster Analysis Identifies Patients With Severe Eosinophilic Asthma Who Achieve Super-Response and Remission With Mepolizumab.

This study identifies two distinct subgroups of patients with severe eosinophilic asthma who respond differently to mepolizumab. Cluster analysis reveals that patients with a family history of asthma, positive skin prick tests and higher baseline lung function have better treatment outcomes, highlighting the value of personalised treatment strategies.

Interleukin 33: a suitable target for biological therapies of COPD?

Because of the relevant importance of the IL-33/ST2 axis in COPD pathobiology, the future results of AERIFY-1 and AERIFY-2 trials could disclose new information about subgroups of responder patients to biologic therapies for this highly prevalent disease https://bit.ly/3USJCUP.

Long-Term Clinical and Sustained REMIssion in Severe Eosinophilic Asthma Treated With Mepolizumab: The REMI-M Study.

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.

Long-term inhaled corticosteroid treatment in patients with chronic obstructive pulmonary disease, cardiovascular disease, and a recent hospitalised exacerbation: The ICSLIFE pragmatic, randomised controlled study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) frequently have cardiovascular comorbidities, increasing the risk of hospitalised COPD exacerbations (H-ECOPDs) or death. This pragmatic study examined the effects of adding an inhaled corticosteroid (ICS) to long-acting bronchodilator(s) (LABDs) in patients with COPD and cardiac comorbidities who had a recent H-ECOPD. METHODS: Patients >60 years of age with COPD and ≥1 cardiac comorbidity, within 6 months after discharge following an H-ECOPD, were randomised to receive LABD(s) with or without ICS, and were followed for 1 year. The primary outcome was the time to first rehospitalisation and/or all-cause death. RESULTS: The planned number of patients was not recruited (803/1032), limiting the strength of the conclusions. In the intention-to-treat population, 89/403 patients (22.1 %) were rehospitalised or died in the LABD group (probability 0.257 [95 % confidence interval 0.206, 0.318]), vs 85/400 (21.3 %) in the LABD+ICS group (0.249 [0.198, 0.310]), with no difference between groups in time-to-event (hazard ratio 1.116 [0.827, 1.504]; p = 0.473). All-cause and cardiovascular mortality were lower in patients receiving LABD(s)+ICS, with relative reductions of 19.7 % and 27.4 %, respectively (9.8 % vs 12.2 % and 4.5 % vs 6.2 %), although the groups were not formally statistically compared for these endpoints. Fewer patients had adverse events in the LABD+ICS group (43.0 % vs 50.4 %; p = 0.013), with 4.9 % vs 5.4 % reporting pneumonia adverse events. CONCLUSIONS: Results suggest addition of ICS to LABDs did not reduce the time-to-combined rehospitalisation/death, although it decreased all-cause and cardiovascular mortality. ICS use was not associated with an increased risk of adverse events, particularly pneumonia.

Type 2 severe asthma: pathophysiology and treatment with biologics.

INTRODUCTION: The hallmark of most patients with severe asthma is type 2 inflammation, driven by innate and adaptive immune responses leading to either allergic or non-allergic eosinophilic infiltration of airways. The cellular and molecular pathways underlying severe type 2 asthma can be successfully targeted by specific monoclonal antibodies. AREAS COVERED: This review article provides a concise overview of the pathophysiology of type 2 asthma, followed by an updated appraisal of the mechanisms of action and therapeutic efficacy of currently available biologic treatments used for management of severe type 2 asthma. Therefore, all reported information arises from a wide literature search performed on PubMed. EXPERT OPINION: The main result of the recent advances in the field of anti-asthma biologic therapies is the implementation of a personalized medicine approach, aimed to achieve clinical remission of severe asthma. Today this accomplishment is made possible by the right choice of the most beneficial biologic drug for the pathologic traits characterizing each patient, including type 2 severe asthma and its comorbidities.

Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis.

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.

Effect of SGLT2-Inhibitors on Polygraphic Parameters in Elderly Patients Affected by Heart Failure, Type 2 Diabetes Mellitus, and Sleep Apnea.

Obstructive sleep apneas (OSAs) and central sleep apneas (CSAs) are the most common comorbidities in Heart Failure (HF) that are strongly associated with all-cause mortality. Several therapeutic approaches have been used to treat CSA and OSA, but none have been shown to significantly improve HF prognosis. Our study evaluated the effects of a 3-months treatment with sodium-glucose cotransporter type 2 inhibitor (SGLT2i) on polygraphic parameters in patients with sleep apnea (SA) and HF, across the spectrum of ejection fraction, not treated with continuous positive air pressure (CPAP). A group of 514 consecutive elderly outpatients with HF, type 2 diabetes mellitus (T2DM) and SA, eligible for treatment with SGLT2i, were included in the investigation before starting any CPAP therapy. The two groups were compared with the t-test and Mann-Whitney test for unpaired data when appropriate. Then, a simple logistic regression model was built using 50% reduction in AHI as the dependent variable and other variables as covariates. A multivariate stepwise logistic regression model was constructed using the variables that linked with the dependent variable to calculate the odds ratio (OR) for the independent predictors associated with the reduction of 50% in AHI. The treated group experienced significant improvements in polygraphic parameters between baseline values and follow-up with reduction in AHI (28.4 ± 12.9 e/h vs. 15.2 ± 6.5 e/h; p < 0.0001), ODI (15.4 ± 3.3 e/h vs. 11.1 ± 2.6 e/h; p < 0.0001), and TC90 (14.1 ± 4.2% vs. 8.2 ± 2.0%; p < 0.0001), while mean SpO2 improved (91. 3 ± 2.3 vs. 93.8 ± 2.5); p < 0.0001. These benefits were not seen in the untreated population. The use of SGLT2i in patients suffering from HF and mixed-type SA not on CPAP therapy significantly contributes to improving polygraphic parameters.

Clinical remission in severe asthma: lights and shadows on an ambitious goal.

PURPOSE OF REVIEW: The aim of this study was Describe the latest evidence related to the concept of clinical remission in patients with severe asthma, focusing on the lights and shadows of this concept. RECENT FINDINGS: The idea of clinical remission in severe asthma patients brings about a significant shift in the way asthma is treated and managed. Although there has yet to be unanimous agreement among various scientific societies on the precise definition, this concept can be extremely useful in advancing the treatment of the disease. SUMMARY: Asthma is a common respiratory condition that affects more than 300 million people globally. It has variable symptoms and severity levels, with about 10% of patients experiencing severe asthma. While there have been advancements in treatment, severe asthma poses significant challenges. Recent approaches have focused on achieving clinical remission, which goes beyond symptom control to address underlying inflammation and biological processes. Clinical remission criteria include the absence of symptoms, reduced medication usage, and normalized inflammatory markers. Various biologic therapies show promise, with some patients achieving remission. However, remission's definition varies globally, hindering standardization and a valid comparison. Standardizing remission criteria and refining predictive factors are crucial for effective asthma management. Overall, achieving clinical remission offers hope for improved long-term outcomes in severe asthma patients.

Complications during Veno-Venous Extracorporeal Membrane Oxygenation in COVID-19 and Non-COVID-19 Patients with Acute Respiratory Distress Syndrome.

Background: Acute respiratory distress syndrome (ARDS) presents a significant challenge in critical care settings, characterized by compromised gas exchange, necessitating in the most severe cases interventions such as veno-venous extracorporeal membrane oxygenation (vv-ECMO) when conventional therapies fail. Critically ill ARDS patients on vv-ECMO may experience several complications. Limited data exist comparing complication rates between COVID-19 and non-COVID-19 ARDS patients undergoing vv-ECMO. This retrospective observational study aimed to assess and compare complications in these patient cohorts. Methods: We retrospectively analyzed the medical records of all patients receiving vv-ECMO for ARDS between March 2020 and March 2022. We recorded the baseline characteristics, the disease course and complication (barotrauma, bleeding, thrombosis) before and after ECMO cannulation, and clinical outcomes (mechanical ventilation and ECMO duration, intensive care unit, and hospital lengths of stay and mortalities). Data were compared between COVID-19 and non-COVID-19 patients. In addition, we compared survived and deceased patients. Results: Sixty-four patients were included. COVID-19 patients (n = 25) showed higher rates of pneumothorax (28% vs. 8%, p = 0.039) with subcutaneous emphysema (24% vs. 5%, p = 0.048) and longer non-invasive ventilation duration before vv-ECMO cannulation (2 [1; 4] vs. 0 [0; 1] days, p = <0.001), compared to non-COVID-19 patients (n = 39). However, complication rates and clinical outcomes post-vv-ECMO were similar between groups. Survival analysis revealed no significant differences in pre-vv-ECMO complications, but non-surviving patients had a trend toward higher complication rates and more pleural effusions post-vv-ECMO. Conclusions: COVID-19 patients on vv-ECMO exhibit higher pneumothorax rates with subcutaneous emphysema pre-cannulation; post-cannulation complications are comparable to non-COVID-19 patients.

Assessment of cephalometric parameters and correlation with the severity of the obstructive sleep apnea syndrome.

BACKGROUND: In individuals diagnosed with obstructive sleep apnea syndrome (OSAS), variations in craniofacial structure have been inconsistently documented, showing differing degrees of alteration between obese and nonobese patients. In addition, sleep disturbance has also been shown to induce disequilibrium in this population of patients. This pilot observational study aimed to assess craniofacial values in obese and nonobese subpopulations of patients with OSAS and their correlation and association with the severity of OSAS. We also assessed whether OSAS patients are characterized by an impaired equilibrium in relation to and associated with the severity of OSAS. METHODS: We included all consecutive adult patients with OSAS. Through cephalometry, we assessed the upper (UPa-UPp) and lower (LPa-LPp) pharynx diameters, superior anterior facial height (Sor-ANS), anterior facial height (ANS-Me), anterior vertical dimension (Sor-Me), posterior facial height (S-Go) and craniovertebral angle (CVA). Furthermore, we analyzed postural equilibrium through a stabilometric examination. RESULTS: Forty consecutive OSAS patients (45% female with a mean age of 56 ± 8.2 years) were included. The subgroup of nonobese patients had a reduced UPa-UPp (p = 0.02). Cephalometric measurements were correlated with the severity of OSAS in nonobese patients, whereas only Sor-ANS was correlated with the severity of OSAS in the obese subpopulation. In the overall population, altered craniofacial values are associated with severe OSAS. Although there are differences in equilibrium between obese and nonobese OSAS patients, the stabilometric measurements were not correlated or associated with OSAS severity. CONCLUSION: Altered craniofacial values and compromised equilibrium in OSAS patients are linked to OSAS severity. Therefore, the management of OSAS should be tailored not only to weight management but also to craniofacial and postural rehabilitation to enhance patient outcomes.

Difficult-To-Treat and Severe Asthma: Can Real-World Studies On Effectiveness of Biological Treatments Change the Lives of Patients?

Many different phenotypes that characterize severe asthma are supported by intricate pathomechanisms called endotypes. The latter are driven by molecular interactions, mediated by intercellular networks. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, real-world studies have confirmed the positive effects of currently available antibodies directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, as well as the receptors of interleukins-4 (IL-4) and 13 (IL-13). The best way to treat severe asthma should be chosen based on the peculiar phenotypic and endotypic traits of each patient. This will lead to relevant improvements in both clinical and functional outcomes. In particular, biological therapies can change the lives of asthma patients with a strong impact on quality of life. Unfortunately, patients with severe non-type-2 asthma, who continue to have pertinent unmet needs, are not receiving satisfactory advances within the context of biological treatments. It is also hopeful that in the next future new therapeutic strategies will be specifically implemented for these people, perhaps offering them the opportunity to improve their current, mostly inadequate asthma management.

Effects of inhaled beclomethasone dipropionate/formoterol fumarate/glycopyrronium on diaphragmatic workload and lung function in uncontrolled asthma: a case report.

Beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) single inhaler extrafine triple therapy is effective for the treatment of uncontrolled asthma. Nevertheless, there is a lack of data about the use of diaphragmatic ultrasonography to monitor adult asthmatics while they are receiving inhaled treatment. We took into consideration a 78-year-old woman complaining of asthma, treated with inhaled corticosteroid/long-acting ß2-adrenergic agonist (ICS/LABA), characterized by an asthma control questionnaire-5 (ACQ-5) score and a lung function test suggestive of uncontrolled asthma. Moreover, a diaphragmatic ultrasound showed signs of high diaphragm workload. Because of these findings, we proposed to our patient a shift toward triple inhaled therapy with BDP/FF/G, and she underwent a second evaluation after 7 days of treatment. Improvements in the diaphragmatic ultrasound parameters, lung function test, and ACQ-5 score were found. In particular, we detected a reduction of thickening fraction (TF), and a normalization of the other diaphragmatic measures, indicative of a decrease in diaphragmatic workload. To our knowledge, this is the first literature report showing concomitant improvements of both lung function tests and diaphragmatic ultrasonography parameters, observed in an adult patient with uncontrolled asthma after short-term treatment with the single inhaler triple therapy BDP/FF/G.

An integrated metabo-lipidomics profile of induced sputum for the identification of novel biomarkers in the differential diagnosis of asthma and COPD.

BACKGROUND: Due to their complexity and to the presence of common clinical features, differentiation between asthma and chronic obstructive pulmonary disease (COPD) can be a challenging task, complicated in such cases also by asthma-COPD overlap syndrome. The distinct immune/inflammatory and structural substrates of COPD and asthma are responsible for significant differences in the responses to standard pharmacologic treatments. Therefore, an accurate diagnosis is of central relevance to assure the appropriate therapeutic intervention in order to achieve safe and effective patient care. Induced sputum (IS) accurately mirrors inflammation in the airways, providing a more direct picture of lung cell metabolism in comparison to those specimen that reflect analytes in the systemic circulation. METHODS: An integrated untargeted metabolomics and lipidomics analysis was performed in IS of asthmatic (n = 15) and COPD (n = 22) patients based on Ultra-High-Pressure Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and UHPLC-tandem MS (UHPLC-MS/MS). Partial Least Squares-Discriminant Analysis (PLS-DA) was applied to resulting dataset. The analysis of main enriched metabolic pathways and the association of the preliminary metabolites/lipids pattern identified to clinical parameters of asthma/COPD differentiation were explored. Multivariate ROC analysis was performed in order to determine the discriminatory power and the reliability of the putative biomarkers for diagnosis between COPD and asthma. RESULTS: PLS-DA indicated a clear separation between COPD and asthmatic patients. Among the 15 selected candidate biomarkers based on Variable Importance in Projection scores, putrescine showed the highest score. A differential IS bio-signature of 22 metabolites and lipids was found, which showed statistically significant variations between asthma and COPD. Of these 22 compounds, 18 were decreased and 4 increased in COPD compared to asthmatic patients. The IS levels of Phosphatidylethanolamine (PE) (34:1), Phosphatidylglycerol (PG) (18:1;18:2) and spermine were significantly higher in asthmatic subjects compared to COPD. CONCLUSIONS: This is the first pilot study to analyse the IS metabolomics/lipidomics signatures relevant in discriminating asthma vs COPD. The role of polyamines, of 6-Hydroxykynurenic acid and of D-rhamnose as well as of other important players related to the alteration of glycerophospholipid, aminoacid/biotin and energy metabolism provided the construction of a diagnostic model that, if validated on a larger prospective cohort, might be used to rapidly and accurately discriminate asthma from COPD.

Features of severe asthma response to anti-IL5/IL5r therapies: identikit of clinical remission.

Introduction: Clinical remission (CliR) achievement has been recognized as a new potential outcome in severe asthma. Nevertheless, we still lack a detailed profile of what features could better identify patients undergoing clinical remission. In this study, we aim to address this issue, tracing a possible identikit of patients fulfilling remission criteria. Methods: We enrolled 266 patients with severe eosinophilic asthma (SEA) treated with a 12-month course of anti-IL5/IL5 receptor (IL5r) monoclonal antibodies. Patients with no exacerbation, OCS withdrawal, ACT ≥ 20 and FEV1 ≥ 80% after 1 year of biologic treatment were classified as in clinical remission. Results: 30.5% of the enrolled patients achieved remission after biologic administration. CliR group showed a lower number of baseline asthma exacerbations and better lung function parameters, with a trend for higher ACT scores and a less frequent history of a positive skin prick test. CliR achievement was unlikely in presence of a higher BMI, a positive skin prick test, an increased number of asthma exacerbations before biologic treatment, anti-muscarinic administration, and a previous diagnosis of EGPA, bronchiectasis or osteoporosis. In contrast, a better lung function, an increased blood eosinophilic count, the presence of chronic rhinosinusitis with nasal polyps and a more frequent use of reliever therapy predicts remission development. Changes in exacerbations number, OCS use, ACT scores and FEV1% between remittent and non-remittent patients arise at specific follow up timepoints and are positively associated with CliR achievement. Discussion: anti-IL5/IL5r biologics can induce CliR in a proportion of patients with SEA. Patients achieving remission demonstrate specific clinical, functional and inflammatory features, as well as a specific moment of improvement in all the CliR items.

Imaging of chronic rhinosinusitis with nasal polyps in the era of biological therapies.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a chronic inflammatory disorder of the sinonasal cavities classified into two major phenotypes: CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). The diagnosis of CRS is based on clinical symptoms associated with imaging and/or nasal endoscopy findings of mucosal inflammation. RECENT FINDINGS: Recently, novel biological therapies have emerged as therapeutic options for CRSwNP. Imaging is helpful in deciding whether surgery is likely to be beneficial and in guiding surgery. It can also help demonstrate a clinical response to medical therapy. However, specific guidelines concerning the role of imaging in CRwNP are lacking. SUMMARY: This article provides a comprehensive and critical multidisciplinary review of the role of conventional radiology, computed tomography (CT), and magnetic resonance imaging (MRI) in the diagnosis and characterization of CRSwNP. Since the complete characterization of nasal polyps on CT or MR images is very challenging, we provide a critical review of the best imaging methods and essential reporting elements used to assess nasal polyps.

Association between non-dipping blood pressure pattern and different glucometabolic profile during oral glucose tolerance test.

It is known that, a not physiological blood pressure (BP) circadian pattern has been associated with increased risk of organ damage and cardiovascular (CV) event. The aim of this study was to assess the association between circadian BP pattern and glucometabolic phenotypes occurring after oral glucose tolerance test (OGTT). We recruited 810 hypertensive Caucasian patients. All participants underwent to OGTT, laboratory test and 24-h ambulatory BP monitoring (ABPM). The analysis of collected data allowed classifying patients based on nocturnal BP profiles into four categories: dippers, non-dippers, extreme dippers, and reverse dippers. Considering the dipping pattern, the proportion of non-dippers in normal glucose tolerance patients with 1-h glucose ≥ 155 mg/dL (NGT ≥ 155) (36.4%) was higher than NGT < 155 (29.6%) and impaired glucose tolerance (IGT) (34.8%), but lower than type 2 diabetes group (T2DM) (52.6%) (p = 0.001). The proportion of dippers was lower in NGT ≥ 155 (47%) and T2DM (34.6%), when compared with NGT < 155 (53.8%) and IGT (51.2%) (p = 0.017). From logistic regression analysis, 1-h glucose ≥ 155 increased the risk of a pathological nocturnal drop in BP by 74%, (OR = 1.740, 95% CI 1.254-2.415, p < 0.0001). In addition, the improvement in 1 unit of Matsuda was responsible for a 3.5% risk decrease (OR = 0.965, 95% CI 0.958-0.971, p < 0.0001), while e-GFR determined a 0.9% risk reduction of nocturnal BP drop (OR = 0.991, 95% CI 0.984-0.999, p = 0.020). Our data demonstrated the existence, in newly diagnosed hypertensive patients, of an association between circadian BP profile and altered glycemic response during OGTT, in particular NGT ≥ 155 subjects are associated with a non-dipper BP pattern, this is clinically relevant because may explain, at least in part, the increased CV risk in this setting of patients.

Real-world characteristics of "super-responders" to mepolizumab and benralizumab in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis.

Background: The current definition of severe eosinophilic asthma (SEA) super-responders to biologic treatment does not include patients with other eosinophil-based comorbidities. Although eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with SEA, we lack data on a possible super-response to biologic treatments in patients suffering from these two diseases. We aim to assess super-responder features in real-life patients with SEA and EGPA treated with mepolizumab and benralizumab. Methods: We enrolled 39 patients with SEA and EGPA eligible for treatment with mepolizumab or benralizumab. Super-responder assessment was performed considering oral corticosteroid (OCS) cessation, lack of exacerbations, forced expiratory volume in 1 s and Asthma Control Test (ACT) improvement. Results: Super-responders showed worse clinical baseline characteristics than non-super-responder patients, with a greater improvement in severe asthma exacerbations, OCS dose reduction and ACT score increase. Definition of super-responders was consistent only considering a 12-month course of monoclonal antibody, lacking sensitivity in earlier evaluations. Conclusion: Mepolizumab and benralizumab are safe and effective in patients with EGPA and SEA, since a consistent proportion of patients show a super-response after 12 months of treatment. Further studies will address specific criteria for super-responder assessment in these patients.