Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps

BackgroundThe efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation.ObjectiveTo assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence.MethodsClinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP.ResultsAmong the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01).ConclusionOur results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation

Effectiveness and safety of anti-IL-5/Rα biologics in eosinophilic granulomatosis with polyangiitis: a two-year multicenter observational study

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia. ObjectiveTo assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5R & alpha;) in EGPA for 24 months. MethodsWe conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/R & alpha; biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed. Results49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all p<0.05), but began to decline from month 12, especially with mepolizumab. Marked reduction in blood eosinophils was registered with mepolizumab (p<0.0001), while benralizumab depleted both eosinophils (p<0.0001) and basophils (p<0.0001). In general, 69.6% (76% benralizumab and 61.9% mepolizumab) of OCS-dependent patients lowered their daily dose by 75%, while 28.3% discontinued these drugs. Immunosuppressants were suspended in 88.2% of cases. Adverse events were reported in 8.2% of patients. ConclusionsThese real-world data suggest that anti-IL-5/R & alpha; biologics are effective and safe in the long-term as add-on treatments for patients with EGPA

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

Background. The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. Patients and methods. Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. Results. In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p p p 1) (p p p < 0.05). Conclusion. The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment

Long-Term Domiciliary High-Flow Nasal Therapy in Patients with Bronchiectasis: A Preliminary Retrospective Observational Case-Control Study

High-flow nasal therapy (HFNT) provides several pathophysiological benefits in chronic respiratory disorders. We aimed to evaluate the effectiveness of long-term HFNT in patients with bronchiectasis (BE). Methods: This is a retrospective bicentric case-control study of outpatients with BE on optimized medical treatment with a severe exacerbation requiring hospitalization in the previous year. Patients on long-term home HFNT (cases) and patients on optimized medical treatment alone (controls) were matched by age, sex, bronchiectasis severity index, and exacerbations in the previous year. Data on BE exacerbations, hospitalizations/year, mucus features, respiratory symptoms, and pulmonary function were collected. The primary outcome was the change from baseline in the exacerbation rates at 12 months between groups. Results: 20 patients in the HFNT group and 20 controls were included. A significant reduction in exacerbations [&minus;1.9 (&minus;2.8 to &minus;0.9), p = 0.0005] and hospitalizations [&minus;0.7 (&minus;1.1 to &minus;0.3), p = 0.0006] was found in the HFNT group vs controls. A slight improvement in pulmonary function [FEV1% +6,1% (+1% to +11.3%) (p = 0.0219), FVC% +4.6% (+0.8% to +8.3%) (p = 0.0188) and FEF25&ndash;75% +13.4 (+11 to +15.9) (p = 0.0189) was also found in the HFNT group compared to controls. Conclusions: In this preliminary study, long-term domiciliary HFNT improved the clinical course of patients with BE

Long-Term Domiciliary High-Flow Nasal Therapy in Patients with Bronchiectasis: A Preliminary Retrospective Observational Case-Control Study

Unlabelled: High-flow nasal therapy (HFNT) provides several pathophysiological benefits in chronic respiratory disorders. We aimed to evaluate the effectiveness of long-term HFNT in patients with bronchiectasis (BE). Methods: This is a retrospective bicentric case-control study of outpatients with BE on optimized medical treatment with a severe exacerbation requiring hospitalization in the previous year. Patients on long-term home HFNT (cases) and patients on optimized medical treatment alone (controls) were matched by age, sex, bronchiectasis severity index, and exacerbations in the previous year. Data on BE exacerbations, hospitalizations/year, mucus features, respiratory symptoms, and pulmonary function were collected. The primary outcome was the change from baseline in the exacerbation rates at 12 months between groups. Results: 20 patients in the HFNT group and 20 controls were included. A significant reduction in exacerbations [-1.9 (-2.8 to -0.9), p = 0.0005] and hospitalizations [-0.7 (-1.1 to -0.3), p = 0.0006] was found in the HFNT group vs controls. A slight improvement in pulmonary function [FEV1% +6,1% (+1% to +11.3%) (p = 0.0219), FVC% +4.6% (+0.8% to +8.3%) (p = 0.0188) and FEF25-75% +13.4 (+11 to +15.9) (p = 0.0189) was also found in the HFNT group compared to controls. Conclusions: In this preliminary study, long-term domiciliary HFNT improved the clinical course of patients with BE

ERS International Congress 2022: highlights from the Respiratory Intensive Care Assembly

Early Career Members of Assembly 2 (Respiratory Intensive Care) attended the 2022 European Respiratory Society (ERS) International Congress in Barcelona, Spain. The conference covered acute and chronic respiratory failure. Sessions of interest to our Assembly members and to those interested in respiratory critical care included the state-of-the-art session on respiratory critical care, the journal session (ERS/Lancet) on acute respiratory distress syndrome (ARDS) phenotyping into precision medicine, and sessions on specificity of coronavirus disease 2019 ARDS and its post-critical care. A symposium on treatment of acute respiratory failure in patients with COPD and innovations in mechanical ventilation either in the intensive care unit or at home were also reported upon. These sessions are summarised in this article

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 &gt;= 20 and FEV1 &gt;= 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

Benralizumab Effectiveness in Severe Eosinophilic Asthma with Co-Presence of Bronchiectasis: A Real-World Multicentre Observational Study

Introduction: The co-presence of bronchiectasis (BE) in severe eosinophilic asthma (SEA) is common. Data about the effectiveness of benralizumab in patients with SEA and BE (SEA + BE) are lacking. Aim: The aim of this study was to evaluate the effectiveness of benralizumab and remission rates in patients with SEA compared to SEA + BE, also according to BE severity. Methods: We conducted a multicentre observational study, including patients with SEA who underwent chest high-resolution computed tomography at baseline. The Bronchiectasis Severity Index (BSI) was used to assess BE severity. Clinical and functional characteristics were collected at baseline and after 6 and 12 months of treatment. Results: We included 74 patients with SEA treated with benralizumab, of which 35 (47.2%) showed the co-presence of bronchiectasis (SEA + BE) with a median BSI of 9 (7–11). Overall, benralizumab significantly improved the annual exacerbation rate (p p p p p = 0.0003], and the daily dose of OCS [−5 mg (0 to −12.5) vs. −12.5 mg (−7.5 to −20), p = 0.0112]. Remission (zero exacerbations + zero OCS) was achieved more frequently in the SEA cohort [66.7% vs. 14.3%, OR 0.08 (95% CI 0.03–0.27), p 1% and FEF25–75% were inversely correlated with BSI (r = −0.36, p = 0.0448 and r = −0.41, p = 0.0191, respectively). Conclusions: These data suggest that benralizumab exerts beneficial effects in SEA with or without BE, although the former achieved less OCS sparing and fewer respiratory-function improvements