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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.
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Antiasmáticos , Asma , Produtos Biológicos , Índice de Gravidade de Doença , Humanos , Asma/tratamento farmacológico , Asma/fisiopatologia , Asma/imunologia , Produtos Biológicos/uso terapêutico , Antiasmáticos/uso terapêutico , Medicina de Precisão , Resultado do TratamentoRESUMO
Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES-Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.
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Síndrome Hipereosinofílica , Síndrome Hipereosinofílica/terapia , Síndrome Hipereosinofílica/imunologia , Síndrome Hipereosinofílica/diagnóstico , Humanos , Itália , Gerenciamento Clínico , Sociedades Médicas , Qualidade de Vida , Alergia e Imunologia , Asma/imunologia , Asma/terapiaRESUMO
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.
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OBJECTIVE: Achieving remission in severe asthma holds paramount importance in elevating patient quality of life and reducing both individual and societal burdens associated with this chronic condition. This study centers on identifying pivotal patient-relevant endpoints through standardized, reproducible methods, while also developing a patient-centric definition of remission, essential for effective disease management. METHODS: A discrete choice experiment (DCE) was conducted to assess patients' perceptions on the four primary criteria for defining severe asthma remission, as outlined by the SANI survey. Additionally, it investigated the correlation between these perceptions and improvements in the doctor-patient therapeutic alliance during treatment decision-making. RESULTS: 249 patients (70% aged between 31-60, 59% women and 82% without other pathologies requiring corticosteroids) prioritize the use of oral corticosteroids (OCS, 48%) and the Asthma Control Test (ACT, 27%) in defining their condition, ranking these above lung function and exacerbations. This preference for OCS stems from its direct role in treatment, tangible tracking, immediate symptom relief, and being a concrete measure of disease severity compared to the less predictable and quantifiable exacerbations. CONCLUSIONS: This study explores severe asthma remission from patients' perspectives using clinician-evaluated parameters. The DCE revealed that most patients highly value OCS and the ACT, prefer moderate improvement, and avoid cortisone cycles. No definitive preference was found for lung function status. Integrating patient-reported information with professional insights is crucial for effective management and future research. Personalized treatment plans focusing on patient preferences, adherence, and alternative therapies aim to achieve remission and enhance quality of life.
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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.
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Purpose: Real-world evidence of benralizumab effectiveness on nasal polyps (NP) and asthma outcomes in patients with severe eosinophilic asthma (SEA) and comorbid chronic rhinosinusitis with NP are limited. The objective of this study was to assess NP and asthma outcomes in benralizumab-treated patients with SEA and comorbid NP in a real-world setting. Patients and Methods: RANS was a retrospective, multi-country observational study (ClinicalTrials.gov: NCT05180357) using medical chart reviews of adults with SEA and comorbid NP. Total NP Score (NPS), SinoNasal Outcome Test-22 (SNOT-22) total score, annualized exacerbation rate (AER), and 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Control Test (ACT) scores during the 12 months pre-index (baseline) and post-index (follow-up) were measured. Clinically meaningful improvement from baseline following treatment, in terms of total NPS (≥1-point reduction), SNOT-22 total (≥8.9-point reduction), ACQ-6 (≥0.5-point reduction) or ACT (≥3-point increase) scores, were reported. Results: A total of 233 patients were included. Baseline mean (standard deviation [SD]) NPS and SNOT-22 total scores were 3.8 (2.4) and 47.5 (22.6), respectively. The mean change (95% confidence interval [CI]) from baseline was -1.2 (-1.7, -0.6) for NPS, and -19.8 (-23.6, -15.9) for SNOT-22. The AER (95% CI) was 1.2 (0.96, 1.41) at baseline and 0.2 (0.13, 0.28) at follow-up. Mean (SD) ACQ-6 and ACT scores were 1.6 (1.3) and 15.0 (5.2) at baseline and 0.8 (1.0) and 22.0 (3.9) at follow-up, respectively. The proportion of patients who achieved clinically meaningful improvements in NPS, SNOT-22 total, ACQ-6, and ACT scores was 49.1%, 67.6%, 56.6%, and 81.1%, respectively. Conclusion: In this real-world study, improvements in NP and asthma outcomes in patients with SEA and comorbid NP were observed during the 12 months following benralizumab initiation.
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BACKGROUND: Pivotal phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection. METHODS: XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48â weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps). RESULTS: Out of 1002 patients analysed, 380 were biologic-experienced. At week 48, 71.3% were exacerbation-free (versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130 out of 274) eliminated their use by week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed. CONCLUSION: In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.
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Antiasmáticos , Anticorpos Monoclonais Humanizados , Asma , Humanos , Masculino , Feminino , Asma/tratamento farmacológico , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos Retrospectivos , Antiasmáticos/uso terapêutico , Adulto , Resultado do Tratamento , Idoso , Eosinófilos , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Eosinofilia/tratamento farmacológicoRESUMO
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.
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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.
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Objective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up. Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period. Setting: Ten Italian academic secondary- and tertiary-care centers. Participants: Patients with a confirmed diagnosis of COPD referring to the outpatient clinics of the participating centers were retrospectively recruited. Primary and Secondary Outcome Measures: Annualized frequency of moderate and severe exacerbations stratified by exacerbation history prior to study enrollment. Patients were classified according to airflow obstruction, GOLD risk categories, and divided in 4 groups: A = no exacerbations; B = 1 moderate exacerbation; C = 1 severe exacerbation; D = ≥2 moderate and/or severe exacerbations. Overall all-cause mortality stratified by age, COPD category, and COPD therapy. A logistic regression model assessed the association of clinical characteristics with mortality. Results: 1111 patients were included (73% males), of which 41.5% had a history of exacerbations. As expected, the proportion of patients experiencing ≥1 exacerbation during follow-up increased according to pre-defined study risk categories (B: 79%, C: 84%, D: 97.4%). Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% of which severe), and 13% died. Deceased patients were significantly older, more obstructed and hyperinflated, and more frequently active smokers compared with survivors. Severe exacerbations were more frequent in patients that died (23.5%, vs 10.2%; p-value: 0.002). Chronic heart failure and ischemic heart disease were the only comorbidities associated with a higher odds ratio (OR) for death (OR: 2.2, p-value: 0.001; and OR: 1.9, p-value: 0.007). Treatment patterns were similar in patients that died and survivors. Conclusion: Patients with a low exacerbation risk are exposed to a significant future risk of moderate/severe exacerbations. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.
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Insuficiência Cardíaca , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Feminino , Estudos de Coortes , Estudos Retrospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Itália/epidemiologiaRESUMO
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.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Lipidômica , Espectrometria de Massas em Tandem/métodos , Escarro/metabolismo , Diagnóstico Diferencial , Reprodutibilidade dos Testes , Projetos Piloto , Estudos Prospectivos , Asma/diagnóstico , Asma/metabolismo , Biomarcadores , Metabolômica/métodos , LipídeosRESUMO
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 1â 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 12â months of treatment. Further studies will address specific criteria for super-responder assessment in these patients.
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Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease linked to type 2 inflammation. Several biologics have demonstrated therapeutic potential for the treatment of this pathology in which IL-4, IL-5 and IL-13 represent the major cytokines involved in the control of eosinophilic respiratory inflammation. 25% of CRSwNP patients relapse after the use of oral glucocorticoids or after surgery and often require several surgeries during their lifetime. In our study we enrolled 14 patients, 11 male and 3 female. The inclusion criteria were: age ≥ 18 years; confirmed diagnosis of chronic rhinosinusitis with severe nasal polyposis; disease severity with NPS Nasal Polyposis Endoscopic Score total score ≥ 5 and/or SNOT-22 ≥ 50; previous treatment failure due to lack of efficacy or discontinuation of systemic corticosteroid therapy and/or non-response or recurrence following surgery. The results presented in this study showed the ability of Dupilumab to improve all the parameters analysed. In particular, statistically significant data were obtained for NPS, SNOT-22, NRS, and IgE in patients exposed to Dupilumab treatment for 24 weeks, highlighting the ability of Dupilumab to produce clinical benefit in CRWwNP patients. In light of these data, the administration of dupilumab every two weeks represents a valid clinical strategy that ENT specialists can adopt for the treatment of adults with inadequately controlled CRSwNP.
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High-flow nasal cannula (HFNC) has several benefits in patients affected by different forms of acute respiratory failure, based on its own mechanisms. We postulated that HFNC may have some advantages over conventional oxygen therapy (COT) on the heart function in patients with acute-on-chronic respiratory failure with concomitant pulmonary hypertension (PH). We therefore designed this retrospective observational study to assess if HFNC improves the right and left ventricle functions and morphologies, arterial blood gases (ABGs), and patients' dyspnea, compared to COT. We enrolled 17 hospitalized patients receiving HFNC, matched with 17 patients receiving COT. Echocardiographic evaluation was performed at the time of admission (baseline) and 10 days after (T10). HFNC showed significant improvements in right ventricular morphology and function, and a reduction in sPAP. However, there were no significant changes in the left heart measurements with HFNC application. Conversely, COT did not lead to any modifications in echocardiographic measurements. In both groups, oxygenation significantly improved from baseline to T10 (in the HFNC group, from 155 ± 47 to 204 ± 61 mmHg while in the COT group, from 157 ± 27 to 207 ± 27 mmHg; p < 0.0001 for both comparisons). In conclusion, these data suggest an improvement of oxygenation with both treatments; however, only HFNC was able to improve the right ventricular morphology and function after 10 days from the beginning of treatment in a small cohort of patients with acute-on-chronic respiratory failure with PH.
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Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry.
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Asma , Humanos , Técnica Delphi , Consenso , Asma/tratamento farmacológico , Itália/epidemiologia , Corticosteroides/uso terapêuticoRESUMO
Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia. Objective: To assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months. Methods: We conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα 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. Results: 49 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. Conclusions: These real-world data suggest that anti-IL-5/Rα biologics are effective and safe in the long-term as add-on treatments for patients with EGPA.
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Asma , Produtos Biológicos , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Humanos , Granulomatose com Poliangiite/tratamento farmacológico , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Imunossupressores/uso terapêutico , Asma/tratamento farmacológicoRESUMO
BACKGROUND: Mepolizumab and benralizumab are monoclonal antibodies directed against anti-IL-5 and anti-IL5R, respectively, and their use reduces the exacerbation rate and maintains oral corticosteroid requirements in severe eosinophilic asthma. Previous studies have tested the therapeutic switch between two biologics with excellent results, further demonstrating the heterogeneity of asthmatic disease and the complexity of the therapeutic choice. It remains unclear if such patients may improve following a switch from mepolizumab to benralizumab. AIMS: Within a multicentre real-life setting, we decided to evaluate the potential effectiveness of a therapeutic switch to benralizumab in patients with severe eosinophilic asthma initially treated with mepolizumab, who experienced sub-optimal responses. The secondary aim was to identify the clinical factors associated with a better response to benralizumab. METHODS: We retrospectively assessed patients with severe eosinophilic asthma treated at six Italian specialist centres, who were switched from mepolizumab to benralizumab following a sub-optimal response, defined as a partial or total lack of clinical remission (i.e., frequent severe exacerbations and/or poorly controlled symptoms and/or higher OCS daily use in patients with a poor or moderate response in the global evaluation of treatment effectiveness scale), after at least 12 months of treatment. RESULTS: Twenty-five patients were included in the analysis (mean age 56.76 ± 11.97 years, 65% female). At 6 months of treatment with benralizumab, the ACT score was significantly higher than the ACT score with mepolizumab (20.24 ± 3.38 vs. 16.77 ± 3.48, p < 0.0001); the mean number of daily SABA inhalations was significantly lower after 6 months and 12 months of treatment with benralizumab than that after treatment with mepolizumab; OCS intake and the prednisone median dosage at 6 months of treatment with benralizumab were significantly lower than those with mepolizumab. Benralizumab treatment resulted in a marked improvement in asthma control, suppressed blood eosinophil levels and reduction in the number of exacerbations in the subgroup of patients with severe eosinophilic asthma and nasal polyposis. CONCLUSIONS: Patients diagnosed with severe eosinophilic asthma who experience a partial response to mepolizumab could benefit from switching to benralizumab, and even more those who have nasal polyposis.
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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 < 0.0001), oral corticosteroids (OCS) consumption (p < 0.0001) and lung function (p < 0.01). After 12 months, significant differences were found between SEA and SEA + BE cohorts in the number of exacerbation-free patients [64.1% vs. 20%, OR 0.14 (95% CI 0.05-0.40), p < 0.0001], the proportion of OCS withdrawal [-92.6% vs. -48.6, 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 < 0.0001]. Changes in FEV1% 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.