Sustained Effectiveness of Benralizumab in Naïve and Biologics-Experienced Severe Eosinophilic Asthma Patients: Results from the ANANKE Study.

Purpose: Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics. Patients and Methods: ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks. Bio-experienced patients were split into omalizumab and mepolizumab subsets according to the type of biologic previously used. Results: A total of 124 (76.5%) naïve and 38 (23.5%) bio-experienced patients were evaluated at index date; 13 patients (34.2%) switched from mepolizumab, 21 patients (55.3%) switched from omalizumab, and four patients (10.5%) received both biologics. The mepolizumab subset was characterized by the longest SEA duration (median of 4.6 years), the highest prevalence of chronic rhinosinusitis with nasal polyposis (CRSwNP) (76.5%), and the greatest oral corticosteroid (OCS) daily dosage (median of 25 mg prednisone equivalent). The omalizumab group showed the highest severe annual exacerbation rate (AER) (1.70). At 96 weeks, treatment with benralizumab reduced any and severe AER by more than 87% and 94%, respectively, across all groups. Lung function was overall preserved, with major improvements observed in the mepolizumab group, which also revealed a 100% drop of the median OCS dose. Asthma Control Test (ACT) score improved in the naïve group while its increment was more variable in bio-experienced patients; among these, a marked difference was noticed between omalizumab and mepolizumab subsets (median ACT score of 23.5 and 18, respectively). Conclusion: Benralizumab promotes durable and profound clinical benefits in naïve and bio-experienced groups, indicating that a nearly complete depletion of eosinophils is highly beneficial in the control of SEA, independently of previous biologic use.

Asthma patients' and physicians' perspectives on the burden and management of asthma: Post-hoc analysis of APPaRENT 1 and 2 to assess predictors of treatment adherence.

INTRODUCTION: Patient adherence to maintenance medication is critical for improving clinical outcomes in asthma and is a recommended guiding factor for treatment strategy. Previously, the APPaRENT studies assessed patient and physician perspectives on asthma care; here, a post-hoc analysis aimed to identify patient factors associated with good adherence and treatment prescription patterns. METHODS: APPaRENT 1 and 2 were cross-sectional online surveys of 2866 adults with asthma and 1883 physicians across Argentina, Australia, Brazil, Canada, China, France, Italy, Mexico, and the Philippines in 2020-2021. Combined data assessed adherence to maintenance medication, treatment goals, use of asthma action plans, and physician treatment patterns and preferences. Multivariable logistic regression models assessed associations between patient characteristics and both treatment prescription (by physicians) and patient treatment adherence. RESULTS: Patient and physician assessments of treatment goals and adherence differed, as did reporting of short-acting ß2-agonist (SABA) prescriptions alongside maintenance and reliever therapy (MART). Older age and greater patient-reported severity and reliever use were associated with better adherence. Patient-reported prescription of SABA with MART was associated with household smoking, severe or poorly controlled asthma, and living in China or the Philippines. CONCLUSIONS: Results revealed an important disconnect between patient and physician treatment goals and treatment adherence, suggesting that strategies for improving patient adherence to maintenance medication are needed, focusing on younger patients with milder disease. High reliever use despite good adherence may indicate poor disease control. Personalised care considering patient characteristics alongside physician training in motivational communication and shared decision-making could improve patient management and outcomes.

Sleep quality burden in chronic rhinosinusitis with nasal polyps and its modulation by dupilumab.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with a substantial burden on patients' quality of life and impaired sleep quality. The most common CRSwNP endotype is characterized by type 2 inflammation, with enhanced production of interleukin (IL)-4, IL-5, and IL-13. Dupilumab is a monoclonal antibody against IL-4 receptor-α, which inhibits both IL-4 and IL-13 signaling, and was recently approved for treatment of CRSwNP. OBJECTIVE: We investigated the effect of dupilumab on the sleep quality of patients with CRSwNP in a real-life setting. METHODS: Patients were evaluated at baseline and after 1 and 3 months of dupilumab treatment by means of the Epworth sleepiness scale (ESS), insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI), and sinonasal outcome test 22 (SNOT-22) sleep domain. RESULTS: A total of 29 consecutive patients were enrolled, and their baseline sleep quality assessment were as follows: ESS of 7.9 (± 4.5); ISI of 13.1 (± 6.2); PSQI of 9.2 (± 3.7); and SNOT-22 sleep domain of 12.1 (± 4.2). Excessive daily sleepiness, insomnia, and globally impaired sleep quality were present in 24.1%, 79.3%, and 93.1% respectively. Treatment with dupilumab was associated with significant improvement in ESS, ISI, PSQI, and SNOT-22 sleep domain with concomitant reduction of the proportion of patients with insomnia and globally impaired sleep quality. CONCLUSION: CRSwNP was associated with a significant impact on global sleep quality, in particular, insomnia, and treatment with dupilumab induced a rapid improvement (after 1 single month of treatment) in all the sleep quality parameters, suggesting that sleep disturbances should be more carefully evaluated as an additional outcome in these patients.

Radiological Versus Clinical 1-Year Outcomes of Dupilumab in Refractory CRSwNP: A Real-Life Study.

OBJECTIVE: To provide real-life evidence on long-term radiological changes in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab, and to assess possible differences between radiological and clinical results in terms of endoscopic findings and Patient-Reported-Outcomes (PROs). METHODS: Consecutive patients treated with dupilumab for recalcitrant CRSwNP were required to undergo CT scan at baseline (T0) and after 12 (T1) since first administration. A group of patients also performed CT scan at 52 weeks (T2) to assess long-term outcomes. At each timepoint, patients underwent nasal endoscopy, assessment of Nasal-Polyp-Score (NPS), Lund-Kennedy-Score (LKS), and had to fill in the 22-item Sinonasal-Outcome-Test (SNOT-22) and Visual-Analogue-Scales (VAS) for sinonasal symptoms. RESULTS: In fifty-three included patients, from T0 to T1 we detected a significant reduction in mean Lund-Mackay score (LM), PROs (SNOT-22, VAS) and endoscopic (NPS, LKS) scores (p < 0.05). In the subset of patients that reached T2 (n = 30), compared to T1, we observed a further significant decrease in mean LM, SNOT-22, VAS, and NPS scores, but not in LKS (p = 0.420). At T1, the highest improvement was observed in PROs (SNOT-22: 56.26%), and polyp size (NPS: 49.83%). Conversely, between T1 and T2, sinus opacification was shown to be the most improved outcome (LM: 36.86%). CONCLUSIONS: Our experience showed that poorly controlled CRSwNP patients treated with dupilumab experienced significant improvement in radiologic, endoscopic and clinical disease severity. While in the initial 3 months, PROs garnered attention for showing earlier effectiveness, radiological outcomes revealed sustained and gradual efficacy in a longer term. LEVEL OF EVIDENCE: Level 4. According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 134:2626-2633, 2024.

Long-Term Efficacy of Mepolizumab at 3 Years in Patients with Severe Asthma: Comparison with Clinical Trials and Super Responders.

The efficacy mepolizumab in severe asthmatic patients is proven in the literature. Primarily to study the effect of mepolizumab on exacerbations, steroid dependence, and the continuation of efficacy in the long term. Secondarily to evaluate the effect of the drug on nasal polyps. Analyzing data from SANI (Severe Asthma Network Italy) clinics, we observed severe asthmatic patients treated with mepolizumab 100 mg/4 weeks, for a period of 3 years. 157 patients were observed. Exacerbations were reduced from the first year (-84.6%) and progressively to 90 and 95% in the second and third ones. Steroid-dependent patients decreased from 54% to 21% and subsequently to 11% in the second year and 6% in the third year. Patients with concomitant nasal polyps, assessed by SNOT-22, showed a 49% reduction in value from baseline to the third year. The study demonstrated the long-term efficacy of mepolizumab in a real-life setting.

Type 2 chronic inflammatory diseases: targets, therapies and unmet needs.

Over the past two decades, significant progress in understanding of the pathogenesis of type 2 chronic inflammatory diseases has enabled the identification of compounds for more than 20 novel targets, which are approved or at various stages of development, finally facilitating a more targeted approach for the treatment of these disorders. Most of these newly identified pathogenic drivers of type 2 inflammation and their corresponding treatments are related to mast cells, eosinophils, T cells, B cells, epithelial cells and sensory nerves. Epithelial barrier defects and dysbiotic microbiomes represent exciting future drug targets for chronic type 2 inflammatory conditions. Here, we review common targets, current treatments and emerging therapies for the treatment of five major type 2 chronic inflammatory diseases - atopic dermatitis, chronic prurigo, chronic urticaria, asthma and chronic rhinosinusitis with nasal polyps - with a high need for targeted therapies. Unmet needs and future directions in the field are discussed.

Mast Cells in Upper and Lower Airway Diseases: Sentinels in the Front Line.

Mast cells (MCs) are fascinating cells of the innate immune system involved not only in allergic reaction but also in tissue homeostasis, response to infection, wound healing, protection against kidney injury, the effects of pollution and, in some circumstances, cancer. Indeed, exploring their role in respiratory allergic diseases would give us, perhaps, novel therapy targets. Based on this, there is currently a great demand for therapeutic regimens to enfeeble the damaging impact of MCs in these pathological conditions. Several strategies can accomplish this at different levels in response to MC activation, including targeting individual mediators released by MCs, blockade of receptors for MC-released compounds, inhibition of MC activation, limiting mast cell growth, or inducing mast cell apoptosis. The current work focuses on and summarizes the mast cells' role in pathogenesis and as a personalized treatment target in allergic rhinitis and asthma; even these supposed treatments are still at the preclinical stage.

COPD and biologic treatment: state of the art.

PURPOSE OF REVIEW: Chronic Obstructive Pulmonary Disease (COPD) is a common, heterogeneous disease associated with abnormal inflammatory response of the lung to noxious particles and gases. The progression of disease leads to respiratory failure, disability and premature death. Although recent progress in reducing the global burden of many chronic disease, such as heart disease and cancer, mortality and morbidity due to COPD continue to increase despite of cigarette smoking worldwide policy. Additionally, diagnostic and therapeutic options have not changed in decades. While patients affected by other respiratory disease may benefit with a personalized precision medicine, thanks to the new biological treatment, to date, there is no biological treatment available for COPD. COPD is generally a neutrophils-predominant disease but approximately 40% of patients with COPD had also an eosinophilic airway inflammation. RECENT FINDINGS: different Phase III trials have been recently performed to evaluate the efficacy and safety of several biological treatments, mostly against eosinophilic inflammation and, to date, some of this trial, still ongoing have promising results. SUMMARY: This review resumes the rationale, the attempts of biological treatment in COPD and latest promising results.

Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study.

BACKGROUND: The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks. METHODS: ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only. RESULTS: Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430-890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: - 94.9%; severe AER: - 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: - 95.9%; severe AER: - 97.5%) and bio-experienced patients (any AER: - 92.4%; severe AER: - 94.0%). CONCLUSIONS: Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients' eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04272463.

Care for Patients with Type-2 Chronic Rhinosinusitis.

In the last 20 years, growing interest in chronic rhinosinusitis (CRS) has become evident in medical literature; nevertheless, it is still difficult to identify the real prevalence of the disease. Epidemiological studies are few and focused on heterogeneous populations and diagnostic methods. Recent research has contributed to identifying CRS as a disease characterized by heterogeneous clinical scenarios, high impact on quality of life, and elevated social costs. Patient stratification with phenotypes and identification of the pathobiological mechanism at the origin of the disease (endotype) and its comorbidities are pivotal in the diagnostic process, and they should be addressed in order to properly tailor treatment. A multidisciplinary approach, shared diagnostic and therapeutic data, and follow-up processes are therefore necessary. Oncological multidisciplinary boards offer models to imitate in accordance with the principles of precision medicine: tracing a diagnostic pathway with the purpose of identifying the patient's immunological profile, monitoring therapeutical processes, abstaining from having only a single specialist involved in treatment, and placing the patient at the center of the therapeutic plan. Awareness and participation from the patient's perspective are fundamental steps to optimize the clinical course, improve quality of life, and reduce the socioeconomic burden.

Evolution in Endoscopic Sinus Surgery: The Adjuvant Role of Reboot Surgery in Patients with Uncontrolled Nasal Symptoms of Eosinophilic Granulomatosis with Polyangiitis.

PURPOSE: In the era of precision medicine, target-therapy with monoclonal antibodies (mAb) has enabled new treatment options in patients affected by eosinophilic granulomatosis with polyangiitis (EGPA). Nevertheless, sometimes unsatisfactory results at a nasal level may be observed. The aim of this study is to describe reboot surgery as a potential adjuvant strategy in multi-operated, yet uncontrolled EGPA patients treated with Mepolizumab. METHODS: We performed reboot surgery on EGPA patients with refractory CRSwNP. We obtained clinical data, nasal endoscopy, nasal biopsy, and symptom severity scores two months before surgery and 12 months after it. Computed tomography (CT) prior to surgery was also obtained. RESULTS: Two patients were included in the study. Baseline sinonasal disease was severe. Systemic EGPA manifestations were under control, and the patients received previous mepolizumab treatment and previous surgery with no permanent benefits on sinonasal symptoms. Twelve months after surgery, nasal symptoms were markedly improved; endoscopy showed an absence of nasal polyps and there were fewer eosinophils at histology. CONCLUSIONS: We presented the first experience of two EGPA patients with refractory CRSwNP who underwent non-mucosa sparing (reboot) sinus surgery; our results support the possible adjuvant role of reboot surgery in this particular subset of patients.

Outcomes of Non-Mucosa Sparing Endoscopic Sinus Surgery (Partial Reboot) in Refractory Chronic Rhinosinusitis with Nasal Polyposis: An Academic Hospital Experience.

OBJECTIVE: The reboot approach could be an effective treatment option to lower recurrence rates (RRs) in recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). The purpose of this study was to investigate RR, recurrence-free survival (RFS), quality of life (QoL) improvement, and oral corticosteroid (OCS) intake in pluri-operated CRSwNP patients treated with partial reboot surgery. METHODS: A consecutive sample of patients with recalcitrant CRSwNP, ineligible for monoclonal antibodies, underwent partial reboot surgery. The 22-item SinoNasal Outcome Test (SNOT-22), Visual Analogue Scales (VAS) scores, OCS intake, and endoscopic Nasal Polyp Score (NPS) were collected pre and postoperatively. The main outcomes were RR and RFS, and comparison of disease-free time with previous endoscopic surgeries. RESULTS: Thirty pluri-operated patients were enrolled. Before the reboot, all had experienced disease recurrence at a mean recurrence time of 8.08 ± 2.83 months after surgery. After reboot, 7 (23.3%) had recurrence at a mean time of 16.67 ± 3.07 months (p = 0.02); none needed additional revision surgery till time of data collection. RR at 12, 18, and 24 months follow-up resulted significantly lower for reboot than other previous surgeries (p = 0.010, p = 0.002, p = 0.016, respectively); RFS difference resulted significant (log-rank test = 4.16; p = 0.04). Differences between pre-and post-operative total and single-items scores of SNOT-22 were significant (p = 0.001), as well as VAS scores (p = 0.001). Before the reboot, 21 patients (70%) took ≥2 OCS courses per year; at the latest follow-up visit, none had taken any course of OCS after reboot. CONCLUSIONS: The reboot approach showed lower RR, longer RFS, improved QoL, and zeroing of OCS uptake. Larger samples and longer follow-up studies are needed to assess long-term efficacy and safety of this procedure. LEVEL OF EVIDENCE: 4: According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 2022. Laryngoscope, 133:1584-1589, 2023.

Cross-Cultural Validation of the Short Version of the Questionnaire of Olfactory Disorders-Negative Statements into Italian: Towards Personalized Patient Care.

Given the high burden of olfactory dysfunction worldwide, recently increased due to the COVID-19 pandemic, it is mandatory to adopt a specific questionnaire to assess the impact of olfactory impairment on quality of life, to be used in clinical practice. The aim of this study is to adapt and validate the short version of the Questionnaire of Olfactory Disorders-Negative Statements (svQOD-NS) for Italian. In the pilot phase, the Italian version of the questionnaire (ITA-svQOD-NS) was produced following recommended guidelines. It was then given to 50 healthy subjects and 50 patients (affected by either nasal polyposis or septal deviation), and results were compared to those of other widely used questionnaires. Test-retest reliability was assessed on a sample of 25 patients. All 50 patients repeated the questionnaires at one and nine months after surgery. The internal consistency of ITA-svQOD-NS measured with Cronbach α was excellent (α = 0.92). The intraclass correlation coefficient for test-retest reliability was also optimal (0.93; 95%CI: 0.90-0.96). Concurrent validity tested with the Pearson coefficient was significant with all other tests administered; also, concerning responsiveness, statistically significant differences were obtained between pre- and post-operative conditions. ITA-svQOD-NS showed high internal consistency, test-retest reliability, and significant correlation with all most-used clinical questionnaires; thus, it can be efficiently applied to assess olfaction-related QoL in the Italian population.

Omalizumab and cancer risk: Current evidence in allergic asthma, chronic urticaria, and chronic rhinosinusitis with nasal polyps.

Omalizumab is a biological drug targeting circulating IgE, approved for use in allergic asthma, chronic spontaneous urticaria, and recently for chronic rhinosinusitis with nasal polyps, with good efficacy in all these settings. Some concerns about omalizumab safety have been raised as its use has been recently linked to potential increased cancer risk. Nevertheless, literature evidence does not support this statement, and clinical studies and evidence from real-world registries and surveillance analysis have consistently reported drug safety.

Nasal cytology as a reliable non-invasive procedure to phenotype patients with type 2 chronic rhinosinusitis with nasal polyps.

Background: The identification of type-2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) acquires a crucial role in the endotypization needed for selecting patients for biological drugs targeting type-2 inflammation: to date, the parameters used include systemic and histological biomarkers. The aim of this study was to investigate whether nasal cytology could identify type-2 inflammation in patients with CRSwNP. Methodology: Thirty-three consecutive patients with CRSwNP underwent nasal cytology sampling at the level of the lower nasal turbinate, and of the polypoid tissue, and surgical polyp tissue sample was collected. The cellularity of the 3 collected samples were compared. Results: Mean nasal polyp tissue, nasal polyps cytology and inferior turbinate cytology eosinophils counts were 43.7 ± 39.6 cells/HPF, 32.8 ± 44.7 cells/HPF and 27.6 ± 58.0 cells/HPF respectively with inferior turbinate cytology eosinophils significantly lower than nasal polyp tissue count (p = 0.007). Both mean nasal polyps cytology eosinophils and mean inferior turbinate cytology eosinophils were significantly higher in patients with type-2 CRSwNP (52.5 ± 67.0 cells/HPF vs 12.2 ± 17.3 cells/HPF, p = 0.012, and 32.0 ± 62.1 cells/HPF vs 2.9 ± 2.9 cells/HPF, p = 0.020 respectively). Conclusions: Nasal cytology is suitable tool for assessing local biomarkers of type-2 inflammation in CRSwNP.

Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy.

Background: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics. Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson's chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons. Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147). Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.

Patient's Adherence and Compliance and Quality of Life During/After VIT.

Adherence and compliance, respectively considered as a more positive, proactive behavior, resulting in a patient's lifestyle change to follow a daily regimen, and, as a more enforced response to an external command, are a critical aspect of any medical therapy, since it is estimated that less than half of the patients who are prescribed a therapy perform it, respecting the doses and duration. As far as aeroallergen immunotherapy is concerned, current data show that adherence is respected in about 50% of subcutaneous immunotherapy and in percentages even lower than 20% in sublingual immunotherapy treatments. This review analyzes the adherence to venom immunotherapy (VIT), in which, given its purpose of preventing potentially fatal anaphylactic reactions to insect stings, this aspect plays a critical role. In fact, protection from stings already takes place when the maintenance dose is reached, but VIT interruption before the recommended duration of 5 years exposes patients to new sting reactions. The data on adherence to VIT are far less abundant than that for aeroallergen immunotherapy. One of the first studies reported poor adherence in Austria, but the model used, consisting in the estimate of the percentage of patients with systemic reactions who accepted or rejected VIT, does not meet the criteria that define adherence to treatment. As for appropriate adherence studies, rates higher than 70% were reported in the United States and European countries. Studies from Italy found that good adherence were observed also in patients receiving, after 4 years of VIT, 3 months extended maintenance dose, as well as in patients treated during the COVID-19 pandemic, <10% of whom stopped VIT. Instead, only 35% of the patients treated for allergy to imported fire ant remained adherent after 1 year of treatment. However, also concerning honeybees and vespids, although adherence is satisfactory, it is possible to further improve it by increasing information and support for patients. Health-related quality of life (HRQL) is an efficient measure to estimate the effectiveness and safety of medical treatment. Tools designed to make patients aware of its improvement through VIT and, in particular, of the complete prevention of the risk of fatal reactions have an important role in reinforcing adherence. However, aspects not yet evaluated, such as the possible relationship between the efficacy of VIT and HRQL or its particular features in patients with mastocytosis, deserve specific studies.

Benralizumab in Patients With Severe Eosinophilic Asthma With and Without Chronic Rhinosinusitis With Nasal Polyps: An ANANKE Study post-hoc Analysis.

Background: Severe 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. Methods: This 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. Results: At 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. Conclusions: This 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.

New Onset of Eosinophilic Granulomatosis with Polyangiitis Following mRNA-Based COVID-19 Vaccine.

Anti-SARS-CoV-2 vaccines are safe and effective, also in individuals with allergic and immune-mediated diseases (IMDs). There are reports suggesting that vaccines may be able to trigger de-novo or exacerbate pre-existing IMDs in predisposed individuals. Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, eosinophilia, and eosinophil-rich granulomatous inflammation in various tissues. We describe the case of a 63-year-old man who experienced cardiac, pulmonary, and neurological involvement one day after the administration of the booster dose of anti-SARS-CoV-2 vaccine (mRNA-1273). A diagnosis of EGPA was made and the patient was treated with high-dose steroids and cyclophosphamide, with a good clinical response. Interestingly, our patient had experienced a significant worsening of his pre-existing asthma six months earlier, just after the first two vaccine shots with the ChAdOx1 anti-SARS-CoV-2 vaccine. It is impossible to know whether our patient would have had developed EGPA following natural SARS-CoV-2 infection or at some point in his life regardless of infectious stimuli. Nevertheless, our report may suggest that caution should be paid during the administration of additional vaccine doses in individuals who experienced an increase in IMD severity that persisted over time following previous vaccine shots.