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BackgroundIndividualized prediction of treatment response may improve the value proposition of advanced treatment options in severe asthma. This study aimed to investigate the combined capacity of patient characteristics in predicting treatment response to mepolizumab in patients with severe asthma.MethodsPatient-level data were pooled from two multinational phase 3 trials of mepolizumab in severe eosinophilic asthma. We fitted penalized regression models to quantify reductions in the rate of severe exacerbations and the 5-item Asthma Control Questionnaire (ACQ5) score. The capacity of 15 covariates towards predicting treatment response was quantified by the Gini index (measuring disparities in treatment benefit) as well as observed treatment benefit within the quintiles of predicted treatment benefit.ResultsThere was marked variability in the ability of patient characteristics to predict treatment response; covariates explained greater heterogeneity in predicting treatment response to asthma control than to exacerbation frequency (Gini index 0.35 v. 0.24). Key predictors for treatment benefit for severe exacerbations included exacerbation history, blood eosinophil count, baseline ACQ5 score and age, and those for symptom control included blood eosinophil count and presence of nasal polyps. Overall, the average reduction in exacerbations was 0.90/year (95%CI, 0.87-0.92) and average reduction in ACQ5 score was 0.18 (95% CI, 0.02-0.35). Among the top 20% of patients for predicted treatment benefit, exacerbations were reduced by 2.23/year (95% CI, 2.03-2.43) and ACQ5 score were reduced by 0.59 (95% CI, 0.19-0.98). Among the bottom 20% of patients for predicted treatment benefit, exacerbations were reduced by 0.25/year (95% CI, 0.16-0.34) and ACQ5 by -0.20 (95% CI, -0.51 to 0.11).ConclusionA precision medicine approach based on multiple patient characteristics can guide biologic therapy in severe asthma, especially in identifying patients who will not benefit as much fr

Cardiac manifestations are the major cause of mortality in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Among these manifestations in EGPA patients, in the literature, there are fewer reports describing bradycardia in EGPA patients than those describing tachycardia. A 50-year-old woman with a history of childhood-onset asthma. At age 28, she was diagnosed with eosinophilic gastroenteritis without the diagnosis of EGPA and was started on a systemic steroid and had maintenance daily dose of 2.5 mg after gradually tapered. She had experiencing dizziness and palpitations 2 weeks after discontinuation of the steroid treatment. At emergency visit, electrocardiography revealed an advanced atrioventricular block of 3:1 or less. Forty-eight minutes after the start of electrocardiography, only a P wave was observed and cardiac arrest occurred for 9 s and temporary emergency pacing was performed immediately. She was diagnosed as EGPA presenting leukocyte count, 16,500/µL, 42.8% of which were eosinophils and sinusitis in computed-tomography. She could be survival by treatment of steroid, following the patient to withdraw from an external pacemaker. She received prednisolone of 60 mg, intravenous cyclophosphamide and intravenous immunoglobulin. She had relapsed presenting peripheral eosinophilia, abdominal and numbness in the toes of the left leg pain, but not arrythmia after tapered of prednisolone. Following additional steroid pulse, she had an increase of prednisolone and continued by intravenous cyclophosphamide, intravenous immunoglobulin and started mepolizumab. We presented a severe case of EGPA presenting an advanced atrioventricular block into cardiac arrest.

BackgroundIndividualized prediction of treatment response may improve the value proposition of advanced treatment options in severe asthma. This study aimed to investigate the combined capacity of patient characteristics in predicting treatment response to mepolizumab in patients with severe asthma.MethodsPatient-level data were pooled from two multinational phase 3 trials of mepolizumab in severe eosinophilic asthma. We fitted penalized regression models to quantify reductions in the rate of severe exacerbations and the 5-item Asthma Control Questionnaire (ACQ5) score. The capacity of 15 covariates towards predicting treatment response was quantified by the Gini index (measuring disparities in treatment benefit) as well as observed treatment benefit within the quintiles of predicted treatment benefit.ResultsThere was marked variability in the ability of patient characteristics to predict treatment response; covariates explained greater heterogeneity in predicting treatment response to asthma control than to exacerbation frequency (Gini index 0.35 v. 0.24). Key predictors for treatment benefit for severe exacerbations included exacerbation history, blood eosinophil count, baseline ACQ5 score and age, and those for symptom control included blood eosinophil count and presence of nasal polyps. Overall, the average reduction in exacerbations was 0.90/year (95%CI, 0.87-0.92) and average reduction in ACQ5 score was 0.18 (95% CI, 0.02-0.35). Among the top 20% of patients for predicted treatment benefit, exacerbations were reduced by 2.23/year (95% CI, 2.03-2.43) and ACQ5 score were reduced by 0.59 (95% CI, 0.19-0.98). Among the bottom 20% of patients for predicted treatment benefit, exacerbations were reduced by 0.25/year (95% CI, 0.16-0.34) and ACQ5 by -0.20 (95% CI, -0.51 to 0.11).ConclusionA precision medicine approach based on multiple patient characteristics can guide biologic therapy in severe asthma, especially in identifying patients who will not benefit as much fr

BackgroundIndividualized prediction of treatment response may improve the value proposition of advanced treatment options in severe asthma. This study aimed to investigate the combined capacity of patient characteristics in predicting treatment response to mepolizumab in patients with severe asthma.MethodsPatient-level data were pooled from two multinational phase 3 trials of mepolizumab in severe eosinophilic asthma. We fitted penalized regression models to quantify reductions in the rate of severe exacerbations and the 5-item Asthma Control Questionnaire (ACQ5) score. The capacity of 15 covariates towards predicting treatment response was quantified by the Gini index (measuring disparities in treatment benefit) as well as observed treatment benefit within the quintiles of predicted treatment benefit.ResultsThere was marked variability in the ability of patient characteristics to predict treatment response; covariates explained greater heterogeneity in predicting treatment response to asthma control than to exacerbation frequency (Gini index 0.35 v. 0.24). Key predictors for treatment benefit for severe exacerbations included exacerbation history, blood eosinophil count, baseline ACQ5 score and age, and those for symptom control included blood eosinophil count and presence of nasal polyps. Overall, the average reduction in exacerbations was 0.90/year (95%CI, 0.87-0.92) and average reduction in ACQ5 score was 0.18 (95% CI, 0.02-0.35). Among the top 20% of patients for predicted treatment benefit, exacerbations were reduced by 2.23/year (95% CI, 2.03-2.43) and ACQ5 score were reduced by 0.59 (95% CI, 0.19-0.98). Among the bottom 20% of patients for predicted treatment benefit, exacerbations were reduced by 0.25/year (95% CI, 0.16-0.34) and ACQ5 by -0.20 (95% CI, -0.51 to 0.11).ConclusionA precision medicine approach based on multiple patient characteristics can guide biologic therapy in severe asthma, especially in identifying patients who will not benefit as much fr

BackgroundIndividualized prediction of treatment response may improve the value proposition of advanced treatment options in severe asthma. This study aimed to investigate the combined capacity of patient characteristics in predicting treatment response to mepolizumab in patients with severe asthma.MethodsPatient-level data were pooled from two multinational phase 3 trials of mepolizumab in severe eosinophilic asthma. We fitted penalized regression models to quantify reductions in the rate of severe exacerbations and the 5-item Asthma Control Questionnaire (ACQ5) score. The capacity of 15 covariates towards predicting treatment response was quantified by the Gini index (measuring disparities in treatment benefit) as well as observed treatment benefit within the quintiles of predicted treatment benefit.ResultsThere was marked variability in the ability of patient characteristics to predict treatment response; covariates explained greater heterogeneity in predicting treatment response to asthma control than to exacerbation frequency (Gini index 0.35 v. 0.24). Key predictors for treatment benefit for severe exacerbations included exacerbation history, blood eosinophil count, baseline ACQ5 score and age, and those for symptom control included blood eosinophil count and presence of nasal polyps. Overall, the average reduction in exacerbations was 0.90/year (95%CI, 0.87-0.92) and average reduction in ACQ5 score was 0.18 (95% CI, 0.02-0.35). Among the top 20% of patients for predicted treatment benefit, exacerbations were reduced by 2.23/year (95% CI, 2.03-2.43) and ACQ5 score were reduced by 0.59 (95% CI, 0.19-0.98). Among the bottom 20% of patients for predicted treatment benefit, exacerbations were reduced by 0.25/year (95% CI, 0.16-0.34) and ACQ5 by -0.20 (95% CI, -0.51 to 0.11).ConclusionA precision medicine approach based on multiple patient characteristics can guide biologic therapy in severe asthma, especially in identifying patients who will not benefit as much fr

Cardiac manifestations are the major cause of mortality in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Among these manifestations in EGPA patients, in the literature, there are fewer reports describing bradycardia in EGPA patients than those describing tachycardia. A 50-year-old woman with a history of childhood-onset asthma. At age 28, she was diagnosed with eosinophilic gastroenteritis without the diagnosis of EGPA and was started on a systemic steroid and had maintenance daily dose of 2.5 mg after gradually tapered. She had experiencing dizziness and palpitations 2 weeks after discontinuation of the steroid treatment. At emergency visit, electrocardiography revealed an advanced atrioventricular block of 3:1 or less. Forty-eight minutes after the start of electrocardiography, only a P wave was observed and cardiac arrest occurred for 9 s and temporary emergency pacing was performed immediately. She was diagnosed as EGPA presenting leukocyte count, 16,500/µL, 42.8% of which were eosinophils and sinusitis in computed-tomography. She could be survival by treatment of steroid, following the patient to withdraw from an external pacemaker. She received prednisolone of 60 mg, intravenous cyclophosphamide and intravenous immunoglobulin. She had relapsed presenting peripheral eosinophilia, abdominal and numbness in the toes of the left leg pain, but not arrythmia after tapered of prednisolone. Following additional steroid pulse, she had an increase of prednisolone and continued by intravenous cyclophosphamide, intravenous immunoglobulin and started mepolizumab. We presented a severe case of EGPA presenting an advanced atrioventricular block into cardiac arrest.

Background: Hypereosinophilic syndrome (HES) is characterized by persistent elevated blood and/or tissue eosinophil levels and eosinophil-mediated organ damage. Presentation is highly heterogenous; patients may experience symptoms affecting multiple organ systems.Objectives: To assess the effects of mepolizumab, which targets interleukin-5, on HES-related symptom burden, based on HES daily symptoms (HES-DS) questionnaire data collected during the Phase III (ClinicalTrials.gov ID: NCT02836496) study of mepolizumab in patients with HES.Methods: Each of the six HES-related symptoms were rated (0-10) daily by patients, recalling worst symptom experience in the prior 24 hours; change from baseline at Week 32 was also calculated for mepolizumab versus placebo.Results: Mepolizumab versus placebo reduced HES-related symptom burden severity in patients with HES at Week 32. Improvements in the median change from baseline scores were seen across all symptom groups except skin for patients treated with mepolizumab; greatest improvement from baseline was observed for breathing symptoms.Conclusion: These data highlight the considerable symptom burden associated with HES and further support the clinical benefits of mepolizumab treatment for these patients., SCOPUS: ar.j, info:eu-repo/semantics/published

BackgroundIndividualized prediction of treatment response may improve the value proposition of advanced treatment options in severe asthma. This study aimed to investigate the combined capacity of patient characteristics in predicting treatment response to mepolizumab in patients with severe asthma.MethodsPatient-level data were pooled from two multinational phase 3 trials of mepolizumab in severe eosinophilic asthma. We fitted penalized regression models to quantify reductions in the rate of severe exacerbations and the 5-item Asthma Control Questionnaire (ACQ5) score. The capacity of 15 covariates towards predicting treatment response was quantified by the Gini index (measuring disparities in treatment benefit) as well as observed treatment benefit within the quintiles of predicted treatment benefit.ResultsThere was marked variability in the ability of patient characteristics to predict treatment response; covariates explained greater heterogeneity in predicting treatment response to asthma control than to exacerbation frequency (Gini index 0.35 v. 0.24). Key predictors for treatment benefit for severe exacerbations included exacerbation history, blood eosinophil count, baseline ACQ5 score and age, and those for symptom control included blood eosinophil count and presence of nasal polyps. Overall, the average reduction in exacerbations was 0.90/year (95%CI, 0.87-0.92) and average reduction in ACQ5 score was 0.18 (95% CI, 0.02-0.35). Among the top 20% of patients for predicted treatment benefit, exacerbations were reduced by 2.23/year (95% CI, 2.03-2.43) and ACQ5 score were reduced by 0.59 (95% CI, 0.19-0.98). Among the bottom 20% of patients for predicted treatment benefit, exacerbations were reduced by 0.25/year (95% CI, 0.16-0.34) and ACQ5 by -0.20 (95% CI, -0.51 to 0.11).ConclusionA precision medicine approach based on multiple patient characteristics can guide biologic therapy in severe asthma, especially in identifying patients who will not benefit as much fr

Dentro de las diversas enfermedades que afectan al ser humano, las cuales implican y comprometen a, en muchas ocasiones, varios órganos y sistemas, se encuentra un grupo de patologías las cuales, paradójicamente, tienen su origen las propias células del cuerpo humano, siendo estas mismas las que producen la clínica correspondiente a las llamadas enfermedades autoinmunes. Como ejemplo claro de este tipo de patologías, se encuentra la granulomatosis eosinofílica con poliangeitis (GEPA) o también conocida bajo el nombre de síndrome de Churg-Strauss. Esta enfermedad autoinmune se define como una vasculitis que afecta principalmente a vasos de pequeño y mediano calibre, afectando de forma más significativa al aparato respiratorio y teniendo a la eosinofilia como uno de los principales factores diagnósticos y pronósticos de dicha patología. Se trata de una enfermedad en la que las opciones de tratamiento son variadas, pero las cuales se están viendo actualizadas por una serie de nuevos fármacos entre los que destaca el protagonista de nuestro estudio, el mepolizumab. Por ello, en este trabajo se ha recogido información que abarca múltiples variables a partir de la historia clínica de 8 pacientes para poder valorar, en función de sus características personales, y en función de las evidencias que nos aportan los nuevos estudios realizados sobre la GEPA y su tratamiento, cómo y en qué proporción podrían haber ayudado en la clínica y en el pronóstico de esta enfermedad, la aparición de nuevos fármacos como el mepolizumab., Grado en Medicina

Dentro de las diversas enfermedades que afectan al ser humano, las cuales implican y comprometen a, en muchas ocasiones, varios órganos y sistemas, se encuentra un grupo de patologías las cuales, paradójicamente, tienen su origen las propias células del cuerpo humano, siendo estas mismas las que producen la clínica correspondiente a las llamadas enfermedades autoinmunes. Como ejemplo claro de este tipo de patologías, se encuentra la granulomatosis eosinofílica con poliangeitis (GEPA) o también conocida bajo el nombre de síndrome de Churg-Strauss. Esta enfermedad autoinmune se define como una vasculitis que afecta principalmente a vasos de pequeño y mediano calibre, afectando de forma más significativa al aparato respiratorio y teniendo a la eosinofilia como uno de los principales factores diagnósticos y pronósticos de dicha patología. Se trata de una enfermedad en la que las opciones de tratamiento son variadas, pero las cuales se están viendo actualizadas por una serie de nuevos fármacos entre los que destaca el protagonista de nuestro estudio, el mepolizumab. Por ello, en este trabajo se ha recogido información que abarca múltiples variables a partir de la historia clínica de 8 pacientes para poder valorar, en función de sus características personales, y en función de las evidencias que nos aportan los nuevos estudios realizados sobre la GEPA y su tratamiento, cómo y en qué proporción podrían haber ayudado en la clínica y en el pronóstico de esta enfermedad, la aparición de nuevos fármacos como el mepolizumab., Grado en Medicina

BACKGROUND: Asthmatics have accelerated lung function decline over time compared with healthy individuals. OBJECTIVE: To evaluate risk factors for accelerated lung function decline. METHODS: In a longitudinal analysis on severe asthmatics enrolled in the Belgian Severe Asthma Registry with at least 2 visits a minimum of 12 months apart, we compared characteristics of patients with and without decline (loss of post-bronchodilation forced expiratory volume in 1 s [FEV1] (% predicted)/y greater than zero) over time. Multiple linear regression was applied to study the factors independently associated with FEV1 decline. RESULTS: In the overall population (n = 318), median annual FEV1 decline was 0.27 (-4.22 to 3.80) % predicted/y over a period of 23 months (12-41 months). Asthma was less controlled at baseline in nondecliners than in decliners (53%). Lung function and residual volume at baseline were higher in the declining group. Decliners presented with increased bronchial reactivity (ie, a lower provocative concentration of methacholine causing a 20% fall in FEV1) at baseline. Twenty-five percent of nondecliners were started on anti-interleukin-5 (anti-IL-5) for severe eosinophilic asthma during the study compared with 10% of decliners. The multivariable model suggested that Asthma Control Questionnaire score at baseline, late-onset asthma, and addition of anti-IL-5 during follow-up were associated with lower FEV1 decline, independently from other variables such as evolution in exacerbations, smoking status, inhaled corticosteroids or oral corticosteroids dose, or add-on anti-immunoglobulin E over time, whereas reversibility to salbutamol and higher FEV1 were associated with accelerated FEV1 decline. CONCLUSIONS: Add-on therapy with anti-IL-5 in severe eosinophilic asthma was associated with an attenuated FEV1 decline. The causality of this observation should, however, be confirmed in future prospective controlled studies.

Dentro de las diversas enfermedades que afectan al ser humano, las cuales implican y comprometen a, en muchas ocasiones, varios órganos y sistemas, se encuentra un grupo de patologías las cuales, paradójicamente, tienen su origen las propias células del cuerpo humano, siendo estas mismas las que producen la clínica correspondiente a las llamadas enfermedades autoinmunes. Como ejemplo claro de este tipo de patologías, se encuentra la granulomatosis eosinofílica con poliangeitis (GEPA) o también conocida bajo el nombre de síndrome de Churg-Strauss. Esta enfermedad autoinmune se define como una vasculitis que afecta principalmente a vasos de pequeño y mediano calibre, afectando de forma más significativa al aparato respiratorio y teniendo a la eosinofilia como uno de los principales factores diagnósticos y pronósticos de dicha patología. Se trata de una enfermedad en la que las opciones de tratamiento son variadas, pero las cuales se están viendo actualizadas por una serie de nuevos fármacos entre los que destaca el protagonista de nuestro estudio, el mepolizumab. Por ello, en este trabajo se ha recogido información que abarca múltiples variables a partir de la historia clínica de 8 pacientes para poder valorar, en función de sus características personales, y en función de las evidencias que nos aportan los nuevos estudios realizados sobre la GEPA y su tratamiento, cómo y en qué proporción podrían haber ayudado en la clínica y en el pronóstico de esta enfermedad, la aparición de nuevos fármacos como el mepolizumab., Grado en Medicina

Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma.

Dentro de las diversas enfermedades que afectan al ser humano, las cuales implican y comprometen a, en muchas ocasiones, varios órganos y sistemas, se encuentra un grupo de patologías las cuales, paradójicamente, tienen su origen las propias células del cuerpo humano, siendo estas mismas las que producen la clínica correspondiente a las llamadas enfermedades autoinmunes. Como ejemplo claro de este tipo de patologías, se encuentra la granulomatosis eosinofílica con poliangeitis (GEPA) o también conocida bajo el nombre de síndrome de Churg-Strauss. Esta enfermedad autoinmune se define como una vasculitis que afecta principalmente a vasos de pequeño y mediano calibre, afectando de forma más significativa al aparato respiratorio y teniendo a la eosinofilia como uno de los principales factores diagnósticos y pronósticos de dicha patología. Se trata de una enfermedad en la que las opciones de tratamiento son variadas, pero las cuales se están viendo actualizadas por una serie de nuevos fármacos entre los que destaca el protagonista de nuestro estudio, el mepolizumab. Por ello, en este trabajo se ha recogido información que abarca múltiples variables a partir de la historia clínica de 8 pacientes para poder valorar, en función de sus características personales, y en función de las evidencias que nos aportan los nuevos estudios realizados sobre la GEPA y su tratamiento, cómo y en qué proporción podrían haber ayudado en la clínica y en el pronóstico de esta enfermedad, la aparición de nuevos fármacos como el mepolizumab., Grado en Medicina

Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma.

Currently, some monoclonal antibodies (mAbs) are being studied for chronic rhinosinusitis with nasal polyps (CRSwNP). Three anti-IL-5 mAb: mepolizumab, reslizumab and benralizumab, have been tested through randomized clinical trials. In this real-life study, we aimed to describe the nasal effects of a cohort of asthmatic adults treated with anti-IL-5 mAb. Methods: We carried out an observational study in adults (≥18 years) on anti-IL-5 mAb treatment. Variables included ACT and SNOT−22 questionnaires, nasal polyps score, blood total IgE levels and blood eosinophil count. Results: Overall, 38 participants were included in the study; 19 patients received mepolizumab, 17 were treated with benralizumab and 2 patients were given reslizumab. There was a statistically significant difference in the ACT and SNOT−22 scores before and after mAb treatment. ACT score increased from 11.05 to 21.5 after treatment (p < 0.001). SNOT−22 decreased from 57 to 37.3 after treatment (p = 0.004). No statistically significant differences between mAb groups were observed regarding the ACT or the SNOT−22 (p = 0.775) response (p = 0.775). In addition, 60.53% of patients obtained a minimal clinically important difference (MCID) in SNOT−22. Conclusions: A significant clinical response based on SNOT−22 score evolution after anti-IL-5 mAb treatment was observed. This study also demonstrated that blood eosinophil count, rather than serum total IgE levels, is the best predictor of asthma symptom improvement, which was assessed through the ACT and SNOT−22 questionnaires.

Currently, some monoclonal antibodies (mAbs) are being studied for chronic rhinosinusitis with nasal polyps (CRSwNP). Three anti-IL-5 mAb: mepolizumab, reslizumab and benralizumab, have been tested through randomized clinical trials. In this real-life study, we aimed to describe the nasal effects of a cohort of asthmatic adults treated with anti-IL-5 mAb. Methods: We carried out an observational study in adults (≥18 years) on anti-IL-5 mAb treatment. Variables included ACT and SNOT−22 questionnaires, nasal polyps score, blood total IgE levels and blood eosinophil count. Results: Overall, 38 participants were included in the study; 19 patients received mepolizumab, 17 were treated with benralizumab and 2 patients were given reslizumab. There was a statistically significant difference in the ACT and SNOT−22 scores before and after mAb treatment. ACT score increased from 11.05 to 21.5 after treatment (p < 0.001). SNOT−22 decreased from 57 to 37.3 after treatment (p = 0.004). No statistically significant differences between mAb groups were observed regarding the ACT or the SNOT−22 (p = 0.775) response (p = 0.775). In addition, 60.53% of patients obtained a minimal clinically important difference (MCID) in SNOT−22. Conclusions: A significant clinical response based on SNOT−22 score evolution after anti-IL-5 mAb treatment was observed. This study also demonstrated that blood eosinophil count, rather than serum total IgE levels, is the best predictor of asthma symptom improvement, which was assessed through the ACT and SNOT−22 questionnaires.

Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown., SCOPUS: ar.j, info:eu-repo/semantics/published

Equal contribution Introduction/Aim: The aim of this real-world study was to compare clinical outcomes of severe asthmatics treated with mepolizumab or benralizumab in a tertiary care severe asthma service setting. Method(s): Patient data (demographic, clinical and lung function) was collected prospectively at two large tertiary hospital severe asthma clinics after treatment initiation with either mepolizumab or benralizumab. Data at baseline and six months were compared using appropriate statistical analyses. Result(s): Overall 118 patients commenced mepolizumab and 102 patients started benralizumab treatment. Six month follow-up data was available for 105 and 72 patients respectively. The majority were female (57.5%) with mean age 59.45 (+/-14.79) years and BMI 30.54 (+/-6.74). Baseline mean pre-bronchodilator FEV1 percentage predicted (preBD-FEV1%) was 58.34% (+/-19.58) and mean Asthma Control Questionnaire (ACQ) score was 3.81 (+/-1.04). Baseline demographics between groups were similar in regard to BMI, age, gender, steroid dose and eosinophil count. However, there were differences suggesting increased severity in the mepolizumab group, where patients had higher ACQ score (3.95+/-1.08 vs 3.65+/-0.96, p=0.03), short-acting beta-agonist (SABA) usage and ED presentations, and lower preBD-FEV1% (55.84+/-19.84 vs 61.21+/-18.97, p=0.04). At six months, there were similar improvements in ACQ score (2.33+/-1.47 vs 2.49+/-1.43, p=0.49). Reduction in steroid dose, SABA usage and fractional exhaled nitric oxide were also similar. The mepolizumab cohort experienced a smaller improvement in preBD-FEV1% (9.33+/-25.24 vs 19.19+/-27.74, p=0.04) and smaller reduction in eosinophil count (-0.49+/-0.35 vs -0.73+/-0.62, p=0.02). However, mepolizumab treatment resulted in a larger reduction in ED presentations (-0.72+/-1.78 vs -0.19+/-0.58, p=0.01). Conclusion(s): Treatment with comparable anti-IL-5 agents, mepolizumab and benralizumab, in severe asthma yielded improvements in seve

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare autoimmune disease characterized by medium and small vessels inflammation. Cardiac vasculitic involvement is one of the most severe manifestations with a significant impact on patients' long-term prognosis: anyway, a specific therapeutic approach for heart involvement in EGPA has not been explored yet. Current regimen consists of a long-term therapy with high dose of glucocorticoids, causing the well-known related-adverse events; immunosuppressive drugs are used in patients with severe manifestations, with some limitations. New therapeutic approaches are needed for patients with refractory disease or contraindications to conventional therapies. The quest for the ideal therapy is going toward a more and more personalized approach: on the one hand, efforts are made to use already existing therapies in the most appropriate way; on the other hand, new insights into EGPA pathogenesis allow the discovery of new targets, as demonstrated by mepolizumab and rituximab, targeting eosinophils, and B-cell compartments. This review summarizes the emerging therapies used in EGPA, focusing on the most recent studies on biologics and analyzing their efficacy and safety.

Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil-reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin-5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add-on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real-world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI-A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases., SCOPUS: re.j, info:eu-repo/semantics/published

Background and aims: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

Background: Anti–IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear. Objective: We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES. Methods: This randomized, multicenter, double-blind, placebo-controlled, phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA-negative HES, experienced 2 or more flares (worsening of HES-related symptoms or blood eosinophil count requiring therapeutic escalation) in the previous 12 months, and had a screening blood eosinophil count greater than or equal to 1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32 weeks, plus existing HES therapy. The primary outcome was the proportion of patients with 1 or more flares (worsening of HES-related symptoms necessitating therapy escalation or ≥2 courses of blinded rescue oral corticosteroids) during the study; in addition, patients who withdrew early from the study were counted as having a flare. Safety end points were also assessed. Results: The proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo (15 of 54 [28%] vs 30 of 54 [56%]; P =.002). Logistic regression analysis was consistent with the primary analysis (odds ratio, 0.28; 95% CI, 0.12-0.64; P =.003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48 of 54 [89%] vs 47 of 54 [87%]). Conclusions: Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified., SCOPUS: ar.j, info:eu-repo/semantics/published

Asthma is a heterogeneous disease with regard to the inflammatory pathways activated. In recent years, biologic drugs (monoclonal antibodies) directed towards specific components of type 2 inflammation have been approved for the treatment of severe asthma. Phenotyping of patients with severe asthma and evaluation of biomarkers have been recommended to help identify patients who are candidates for treatment with biologics and to monitor treatment responses. Fractional exhaled Nitric Oxide (FeNO) is a biomarker of type 2 inflammation in asthma, signaling activation of Interleukin (IL)-4/IL-13 pathway. FeNO could be useful to assess treatment response or identify candidates for a specific drug that acts on type 2 inflammation mechanisms linked to Nitric Oxide (NO) production, such as the IL-4/IL-13 pathway or upstream processes. The value of FeNO as a biomarker predictive of responses to the biologics available for treating severe asthma is discussed based on the published studies at the moment of the review.

The increasing use of advanced biologic therapies for patients with severe asthma is transforming the standard of care, clinic workflow, and the clinic business model. Expanded patient access to at-home injection treatment possibilities with some biologics has the potential to improve patient adherence and outcomes. Simultaneously, transition to the home setting can address the escalating costs that limit access for certain patients and healthcare facilities. Such moves come with recognized risks. Garnering input from physicians and other healthcare specialists as well as scrutinizing best practice position statements are vital to implementing truly patient-safe and cost-effective strategies in medicine. Mepolizumab is the first anti-IL-5 inhibitor to receive FDA approval in late 2015. We focus on this injectable medication and discuss the specific indications and contraindications for transitioning patients to at-home injection with mepolizumab. In doing so, we review our recent real-world experiences in the University of California, Davis and Loma Linda University severe asthma clinics, which can provide the foundation for building a comprehensive clinic and home-based biologics asthma program. In addition, we offer insight into the barriers to implementing a successful program and strategies for overcoming them.

Background: Global Initiative for Asthma step 5 therapies (GINA-5), other than inhaled corticosteroids and long-acting beta-agonists in fixed dose combinations (ICS/LABA FDC), often entail more expensive (eg, monoclonal biologics) or less safe (eg, maintenance oral corticosteroids [OCS]) treatments. It is therefore important to assess poor inhaler adherence as a possible cause of suboptimal response to ICS/LABA FDC before additional GINA-5. Objective(s): To determine rates of, and time to, additional GINA-5 after first-year ICS/LABA FDC use, and their association with inhaler adherence. Method(s): Patients initiating ICS/LABA FDC between 2013 and 2017 were identified from Australian national dispensing data. Group-based trajectory modeling was used to estimate medication adherence patterns. Multivariable Cox proportional hazards models were used to examine the association between adherence trajectories and GINA-5 addition during 2-year follow-up. Result(s): In total, 3062 new ICS/LABA FDC users were identified, of whom 120 (3.9%) received additional GINA-5 (OCS: 89; long-acting muscarinic antagonists: 39; biologics: <3). Mean time to commencing additional GINA-5 was 705.2 (standard deviation, 1.7) days. Adherence trajectories were nonpersistent use (20%), seasonal use (8%), poor adherence (58%), and good adherence (13%). Although poor adherence was associated with longer time to additional GINA-5 (adjusted hazard ratio: 0.58; 95% confidence interval: 0.35-0.95), over 80% of additional GINA-5 was commenced in poorly adherent patients. Use of >=2 OCS/antibiotic courses also predicted additional GINA-5. Conclusion(s): Almost 1 in 20 people with asthma commenced additional GINA-5 after ICS/LABA initiation, most of whom (>80%) were poorly adherent to inhaled preventers. There is a substantial unmet need for inhaler adherence to be addressed before prescribing additional GINA-5.Copyright © 2019 American Academy of Allergy, Asthma & Immunology

Introduction: Severe eosinophilic asthma is an incapacitating disease. Mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, proved to be effective as an add-on therapy in patients with severe eosinophilic asthma. However, only data from randomized controlled trials are available and real world data are lacking. Methods: A retrospective observational longitudinal study was conducted in a real world cohort of patients with severe eosinophilic asthma treated with mepolizumab. The primary objective was to determine response rate, based on a global evaluation of treatment effectiveness by the treating pulmonologist. Secondary objectives were to assess exacerbation frequency, systemic maintenance glucocorticoid usage, Asthma Control Questionnaire (ACQ), lung function, and adverse events. Results: Seventy-eight patients were included. Treatment with mepolizumab was considered beneficial and was therefore continued in 75.6% of patients 12 months from the initiation of mepolizumab. The most common reason for drop-out was insufficient response. Secondary objectives: 12 months from the initiation of mepolizumab there was a decrease of 3.2 (CI 2.5–4.1; p < 0.001) severe asthma exacerbations per year, a decrease of ACQ of 0.80 points (CI 0.49–1.12; p < 0.001), and an increase of 3.7 (CI 0.3–7.2; p = 0.034) percent of predicted FEV1 compared to baseline. At baseline 51.3% of patients were treated with systemic glucocorticoid maintenance therapy, compared to 15.4% (p < 0.001) of patients 12 months from the initiation of mepolizumab. No serious adverse events considered to be related to mepolizumab were reported. Conclusion: This study confirms that mepolizumab add-on therapy is effective and safe in a real world cohort of patients with severe eosinophilic asthma.

Background: Global Initiative for Asthma step 5 therapies (GINA-5), other than inhaled corticosteroids and long-acting beta-agonists in fixed dose combinations (ICS/LABA FDC), often entail more expensive (eg, monoclonal biologics) or less safe (eg, maintenance oral corticosteroids [OCS]) treatments. It is therefore important to assess poor inhaler adherence as a possible cause of suboptimal response to ICS/LABA FDC before additional GINA-5. Objective(s): To determine rates of, and time to, additional GINA-5 after first-year ICS/LABA FDC use, and their association with inhaler adherence. Method(s): Patients initiating ICS/LABA FDC between 2013 and 2017 were identified from Australian national dispensing data. Group-based trajectory modeling was used to estimate medication adherence patterns. Multivariable Cox proportional hazards models were used to examine the association between adherence trajectories and GINA-5 addition during 2-year follow-up. Result(s): In total, 3062 new ICS/LABA FDC users were identified, of whom 120 (3.9%) received additional GINA-5 (OCS: 89; long-acting muscarinic antagonists: 39; biologics: <3). Mean time to commencing additional GINA-5 was 705.2 (standard deviation, 1.7) days. Adherence trajectories were nonpersistent use (20%), seasonal use (8%), poor adherence (58%), and good adherence (13%). Although poor adherence was associated with longer time to additional GINA-5 (adjusted hazard ratio: 0.58; 95% confidence interval: 0.35-0.95), over 80% of additional GINA-5 was commenced in poorly adherent patients. Use of >=2 OCS/antibiotic courses also predicted additional GINA-5. Conclusion(s): Almost 1 in 20 people with asthma commenced additional GINA-5 after ICS/LABA initiation, most of whom (>80%) were poorly adherent to inhaled preventers. There is a substantial unmet need for inhaler adherence to be addressed before prescribing additional GINA-5.Copyright © 2019 American Academy of Allergy, Asthma & Immunology

The increasing use of advanced biologic therapies for patients with severe asthma is transforming the standard of care, clinic workflow, and the clinic business model. Expanded patient access to at-home injection treatment possibilities with some biologics has the potential to improve patient adherence and outcomes. Simultaneously, transition to the home setting can address the escalating costs that limit access for certain patients and healthcare facilities. Such moves come with recognized risks. Garnering input from physicians and other healthcare specialists as well as scrutinizing best practice position statements are vital to implementing truly patient-safe and cost-effective strategies in medicine. Mepolizumab is the first anti-IL-5 inhibitor to receive FDA approval in late 2015. We focus on this injectable medication and discuss the specific indications and contraindications for transitioning patients to at-home injection with mepolizumab. In doing so, we review our recent real-world experiences in the University of California, Davis and Loma Linda University severe asthma clinics, which can provide the foundation for building a comprehensive clinic and home-based biologics asthma program. In addition, we offer insight into the barriers to implementing a successful program and strategies for overcoming them.

Introduction: Idiopathic chronic eosinophilic pneumonia (ICEP) is an orphan lung disease characterized by concomitant systemic and local eosinophilia, along with bilateral lung infiltrates. Symptoms include dyspnea of subacute/chronic onset, cough, and general systemic signs. Although all patients do respond to oral corticosteroids, relapse rate is very high, which highlights the need for alternative therapies in case of relapsing ICEP. Mepolizumab is a fully humanized antibody directed against interleukin 5, a key growth factor of eosinophils. In the present study, we retrospectively studied the effect of off-label use of mepolizumab for relapsing ICEP. Materials and Methods: All data from patients treated with mepolizumab for relapsing ICEP were included in our database and diagnoses were reviewed. We analyzed the effect of treatment on relapse rate, oral corticosteroids (OCS) use, and lung lesions on high-resolution computed tomography (HRCT). Results: We included ten patients in the final analysis, with a median follow-up of 9 months after initiation of mepolizumab. Beside its expected effect on circulating eosinophils, treatment with mepolizumab was associated with a significant reduction of annual rate of exacerbations and a reduced consumption of corticosteroids. We also observed a remission of lung lesions on follow-up HRCT. Conclusions: In this open-label retrospective study, treatment of ICEP with mepolizumab was associated with a reduction of relapses, OCS use, and the disappearance of lung infiltrates., SCOPUS: ar.j, info:eu-repo/semantics/published

Objetivo: Mepolizumab está indicado como tratamiento adicional del asma eosinofílica refractaria grave. Las diferencias observadas en subgrupos poblacionales según recuento eosinofílico plasmático, existencia de pacientes con altos niveles de inmunoglobulina E candidatos a omalizumab y mepolizumab, e impacto económico de mepolizumab obligan a realizar estudios económicos para tomar decisiones clínicas eficientes. El objetivo fue realizar un análisis de coste/eficacia e impacto presupuestario de mepolizumab. Método: Se realizó la comparación de costes e impacto presupuestario del uso de mepolizumab desde la perspectiva del Sistema Nacional de Salud. Las alternativas valoradas fueron corticosteroides sistémicos inhalados + agonista β2 de larga duración y/o corticosteroides sistémicos orales en pacientes con asma alérgica grave no mediada por inmunoglobulina E, y este tratamiento junto a omalizumab en pacientes con asma eosinofílica alérgica mediada por inmunoglobulina E. La eficacia se evaluó mediante exacerbaciones clínicamente relevantes evitadas. Se valoraron los costes directos asociados a exacerbación. Resultados: El coste incremental medio de mepolizumab respecto a omalizumab es de 797 euros por paciente y año. Considerando precio alternativo con descuento de omalizumab, incluir mepolizumab para pa cientes con asma eosinofílica alérgica y mediada por inmunoglobulina E supondría incrementar el gasto público de 2,3 a 4,6 millones de euros. Teniendo en cuenta el precio notificado de omalizumab, la introducción gradual de mepolizumab en el Sistema Nacional de Salud supondría ahorrar 3,6 millones de euros en tres años. Para pacientes con asma grave no mediada por inmunoglobulina E, el coste/exacerbación evitada al añadir mepolizumab es de 15.085 euros, con un impacto presupuestario en tres años de 578,4 millones de euros, asumiendo una penetración progresiva de mepolizumab en el mercado. En los pacientes con ≥500 eosinófilos/µl, este coste disminuye a 7.767 euros por, Objective: Mepolizumab is indicated as additional treatment of severe refractory eosinophilic asthma. Differences in subgroups according to plasmatic eosinophil count, existence of patients with high levels of immunoglobulin E candidates for omalizumab and mepolizumab, and budget impact of mepolizumab require economic studies for efficient clinical decisions. The objective was to perform a cost-efficacy and budget impact analysis of mepolizumab. Method: An analysis of comparison of costs and budgetary impact of use of mepolizumab has been performed from National Health System perspective. Evaluated alternatives were inhaled systemic corticosteroids + long-acting β2-agonist and/or oral systemic corticosteroids in patients with severe allergic asthma not mediated by immunoglobulin E, and the same treatment associated with omalizumab in patients with immunoglobulin E-mediated allergic eosinophilic asthma. Efficacy was assessed by clinically relevant exacerbations avoided. Direct costs associated with exacerbation were assessed Results: An average incremental cost of 797 euros/patient-year was estimated. Considering alternative price with discount for omalizumab, including mepolizumab for patients with immunoglobulin E-mediated allergic eosinophilic asthma would increase public spending from 2.3 to 4.6 million euros. According reported price for omalizumab, gradual introduction of mepolizumab into the National Health System would save 3.6 million euros in three years. For patients with immunoglobulin E-not mediated severe asthma, adding mepolizumab presented a cost/exacerbation avoided of 15,085 euros and a budgetary impact for three years of 578.4 million euros according a progressive penetration of mepolizumab in market. In patients with ≥ 500 eosinophils/μL, cost/exacerbation avoided is reduced to 7,767 euros and the budgetary impact is 183.2 million euros in three years according progressive penetration of mepolizumab. Conclusions: With analysis of cost comparison o

This article provides an overview of outstanding sessions that were supported by Assembly 9 during the recent European Respiratory Society International Congress in Paris, France. Session content was mainly targeted at allied health professionals such as respiratory physiologists, respiratory physiotherapists and respiratory nurses. Recent developments and novel findings related to pulmonary function testing, respiratory muscle function assessments and treatment, and multidimensional and multidisciplinary approaches to the assessment and management of dyspnoea were the focus of these sessions and are summarised here.Copyright © ERS 2019.

Objetivo: Mepolizumab está indicado como tratamiento adicional del asma eosinofílica refractaria grave. Las diferencias observadas en subgrupos poblacionales según recuento eosinofílico plasmático, existencia de pacientes con altos niveles de inmunoglobulina E candidatos a omalizumab y mepolizumab, e impacto económico de mepolizumab obligan a realizar estudios económicos para tomar decisiones clínicas eficientes. El objetivo fue realizar un análisis de coste/eficacia e impacto presupuestario de mepolizumab. Método: Se realizó la comparación de costes e impacto presupuestario del uso de mepolizumab desde la perspectiva del Sistema Nacional de Salud. Las alternativas valoradas fueron corticosteroides sistémicos inhalados + agonista β2 de larga duración y/o corticosteroides sistémicos orales en pacientes con asma alérgica grave no mediada por inmunoglobulina E, y este tratamiento junto a omalizumab en pacientes con asma eosinofílica alérgica mediada por inmunoglobulina E. La eficacia se evaluó mediante exacerbaciones clínicamente relevantes evitadas. Se valoraron los costes directos asociados a exacerbación. Resultados: El coste incremental medio de mepolizumab respecto a omalizumab es de 797 euros por paciente y año. Considerando precio alternativo con descuento de omalizumab, incluir mepolizumab para pa cientes con asma eosinofílica alérgica y mediada por inmunoglobulina E supondría incrementar el gasto público de 2,3 a 4,6 millones de euros. Teniendo en cuenta el precio notificado de omalizumab, la introducción gradual de mepolizumab en el Sistema Nacional de Salud supondría ahorrar 3,6 millones de euros en tres años. Para pacientes con asma grave no mediada por inmunoglobulina E, el coste/exacerbación evitada al añadir mepolizumab es de 15.085 euros, con un impacto presupuestario en tres años de 578,4 millones de euros, asumiendo una penetración progresiva de mepolizumab en el mercado. En los pacientes con ≥500 eosinófilos/µl, este coste disminuye a 7.767 euros por, Objective: Mepolizumab is indicated as additional treatment of severe refractory eosinophilic asthma. Differences in subgroups according to plasmatic eosinophil count, existence of patients with high levels of immunoglobulin E candidates for omalizumab and mepolizumab, and budget impact of mepolizumab require economic studies for efficient clinical decisions. The objective was to perform a cost-efficacy and budget impact analysis of mepolizumab. Method: An analysis of comparison of costs and budgetary impact of use of mepolizumab has been performed from National Health System perspective. Evaluated alternatives were inhaled systemic corticosteroids + long-acting β2-agonist and/or oral systemic corticosteroids in patients with severe allergic asthma not mediated by immunoglobulin E, and the same treatment associated with omalizumab in patients with immunoglobulin E-mediated allergic eosinophilic asthma. Efficacy was assessed by clinically relevant exacerbations avoided. Direct costs associated with exacerbation were assessed Results: An average incremental cost of 797 euros/patient-year was estimated. Considering alternative price with discount for omalizumab, including mepolizumab for patients with immunoglobulin E-mediated allergic eosinophilic asthma would increase public spending from 2.3 to 4.6 million euros. According reported price for omalizumab, gradual introduction of mepolizumab into the National Health System would save 3.6 million euros in three years. For patients with immunoglobulin E-not mediated severe asthma, adding mepolizumab presented a cost/exacerbation avoided of 15,085 euros and a budgetary impact for three years of 578.4 million euros according a progressive penetration of mepolizumab in market. In patients with ≥ 500 eosinophils/μL, cost/exacerbation avoided is reduced to 7,767 euros and the budgetary impact is 183.2 million euros in three years according progressive penetration of mepolizumab. Conclusions: With analysis of cost comparison o

This article provides an overview of outstanding sessions that were supported by Assembly 9 during the recent European Respiratory Society International Congress in Paris, France. Session content was mainly targeted at allied health professionals such as respiratory physiologists, respiratory physiotherapists and respiratory nurses. Recent developments and novel findings related to pulmonary function testing, respiratory muscle function assessments and treatment, and multidimensional and multidisciplinary approaches to the assessment and management of dyspnoea were the focus of these sessions and are summarised here.Copyright © ERS 2019.

Introducción. En los últimos años, se han comercializado diferentes fármacos biológicos dirigidos a dianas específicas del asma, como el omalizumab y mepolizumab. Ambos tienen la indicación de asma refractaría grave, que suponen un 5-10% de los pacientes. Objetivos. El objetivo principal fue evaluar la efectividad de omalizumab y mepolizumab en pacientes con asma refractaría grave, y los secundarios: descripción de la población en tratamiento, evaluación de la adecuación de la prescripción y evaluación de la seguridad. Metodología. Estudio observacional, unicéntrico, retrospectivo. Se incluyeron todos los pacientes diagnosticados de asma refractaría grave en tratamiento con omalizumab y mepolizumab durante el periodo de enero de 2017 hasta febrero de 2018 en la UGC de Neumología. La efectividad de ambos fármacos se valoró, en la primera visita y al año del tratamiento, definiendo una respuesta clínica adecuada como: al menos un 50% menos de exacerbaciones que necesitan corticoides sistémicos, reducción clínicamente significativa en el uso continuado de corticoides orales y mejora del control del asma. La adecuación de las prescripciones se valoró teniendo en cuenta los criterios que se acordaron en la CFT del Hospital de Valme. Para la seguridad se registraron los eventos adversos descritos. Resultados. El perfil del paciente con asma refractaria aguda es mujer de edad media, no fumadora y con una mediana de 18 años desde el diagnóstico, refractaria a alternativas terapéuticas. La adecuación de las prescripciones fue buena. En el caso del omalizumab, la mayoría de los pacientes manifestaron una respuesta clínica adecuada en las dos consultas. En el caso del mepolizumab, la efectividad solo se pudo valorar en la primera visita donde el 100% de los pacientes mostraron una respuesta clínica adecuada. Ambos fármacos presentaron una efectividad aceptable. Respecto a la seguridad, la mayoría de los eventos adversos coincidieron con los descritos en la ficha técnica.

Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that binds to free IL-5. It induces bone marrow eosinophil maturation arrest and decreases eosinophil progenitors and subsequent maturation in the blood and bronchial mucosa. Its use has been extensively studied in severe eosinophilic asthma at a dose of 100 mg subcutaneously (SC) every 4 weeks and, more recently, in other hypereosinophilic syndromes. Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic vasculitis that may involve multiple organs. Characteristic clinical manifestations are asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Among the numerous pathways involved in the pathogenesis of EGPA, the Th-2 phenotype has a main role, as suggested by the prominence of the asthmatic component, in triggering the release of key cytokines for the activation, maturation and survival of eosinophils. In particular, IL-5 is highly increased in active EGPA and its inhibition can represent a potential therapeutic target. In this scenario, mepolizumab may play a therapeutic role. After some positive preliminary observations on the use of mepolizumab in small case series of EGPA patients with refractory or relapsing disease despite standard of care treatment, a randomized controlled trial was published in 2017. Mepolizumab at a dose of 300 mg administered by SC injection every 4 weeks proved effective in prolonging the period of remission of the disease, allowing for reduced steroid use. The positive results of this study, which met both of the primary endpoints, led to the approval in the USA of mepolizumab in adult patients with EGPA by the Food and Drug Administration in 2017. Therefore, mepolizumab can be officially considered as an add-on therapy with steroid-sparing effect in cases of relapsing or refractory EGPA. However, the most appropriate dose and duration of therapy still need to be determined. Future studies on larger multinational populations with prol

Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that binds to free IL-5. It induces bone marrow eosinophil maturation arrest and decreases eosinophil progenitors and subsequent maturation in the blood and bronchial mucosa. Its use has been extensively studied in severe eosinophilic asthma at a dose of 100 mg subcutaneously (SC) every 4 weeks and, more recently, in other hypereosinophilic syndromes. Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic vasculitis that may involve multiple organs. Characteristic clinical manifestations are asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Among the numerous pathways involved in the pathogenesis of EGPA, the Th-2 phenotype has a main role, as suggested by the prominence of the asthmatic component, in triggering the release of key cytokines for the activation, maturation and survival of eosinophils. In particular, IL-5 is highly increased in active EGPA and its inhibition can represent a potential therapeutic target. In this scenario, mepolizumab may play a therapeutic role. After some positive preliminary observations on the use of mepolizumab in small case series of EGPA patients with refractory or relapsing disease despite standard of care treatment, a randomized controlled trial was published in 2017. Mepolizumab at a dose of 300 mg administered by SC injection every 4 weeks proved effective in prolonging the period of remission of the disease, allowing for reduced steroid use. The positive results of this study, which met both of the primary endpoints, led to the approval in the USA of mepolizumab in adult patients with EGPA by the Food and Drug Administration in 2017. Therefore, mepolizumab can be officially considered as an add-on therapy with steroid-sparing effect in cases of relapsing or refractory EGPA. However, the most appropriate dose and duration of therapy still need to be determined. Future studies on larger multinational populations with prol

Improved understanding of the contribution of eosinophils to various chronic inflammatory conditions, most notably allergic asthma, has encouraged development of monoclonal antibodies specifically targeting mediators and surface receptors involved in eosinophil expansion and activation. The pivotal role of interleukin-5 (IL-5) in eosinophil biology, its high specificity for this leukocyte subset, and its involvement in the majority of eosinophilic conditions make it a very enticing target for treatment of eosinophil-mediated disorders. Two types of antibodies have been developed to target eosinophils: antibodies against IL-5 (mepolizumab and reslizumab), and an antibody against the IL-5-receptor-alpha-chain (IL-5Ra) (benralizumab). Both types of antibodies prevent IL-5 from engaging its receptor and in addition, anti-IL-5Ra antibodies induce target-cell lysis. They have been shown to reduce circulating eosinophil counts rapidly in humans with various disorders. Herein, a brief overview of the role of IL-5 in eosinophil biology will be presented, followed by a description of the development and characteristics of antibodies targeting IL-5 or its receptor. Results of clinical trials evaluating the efficacy and safety of these new antibodies in diseases (other than eosinophilic asthma) with prominent tissue eosinophilia are reviewed, followed by safety considerations and potential future applications., SCOPUS: ar.j, SCOPUS: re.j, info:eu-repo/semantics/published

SCOPUS: ed.j, info:eu-repo/semantics/published

Purpose of review Eosinophil granulocyte myeloid cells are increased in atopic and nonatopic rhinitis, chronic rhinosinusitis (CRS) and atopic keratoconjunctivitis, diseases of the upper respiratory tract. Eosinophils contain several basic granule proteins, the best known being the eosinophil cationic protein (ECP). ECP is a cytotoxic, profibrotic ribonuclease, which is found deposited in these eosinophil-related diseases and is often used in parallel with blood eosinophilia to monitor those diseases. The contribution of eosinophils and their granule proteins to disease pathogenesis have been debated; recent findings might bring these cells to the center of attention. Recent findings Novel mediators of atopic disease, interleukin-17 (IL-17) and IL-33 have been found in the upper respiratory tract. These cytokines stimulate eosinophils to survival and degranulation, IL-17 via granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-33 directly. Transforming growth factor (TGF)-beta has been found in CRS and atopic keratoconjunctivitis mucosa, its production possibly stimulated by ECP. ECP is detected in nasal mucosa of local allergic reactions, entopy, in rhinitis and CRS. ECP might be released from freely circulating eosinophil granules or in association with eosinophil mitochondrial DNA, both means of release for pathogen defence. Summary Novel evidence suggests that eosinophils and ECP might have new prominent roles in development of diseases of the upper respiratory tract.

Background: Mepolizumab, a monoclonal anti-IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor α fusion (F/P)-negative hypereosinophilic syndrome (HES). Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by marked overproduction of IL-5 by dysregulated T cells. Objective: To determine whether patients with L-HES respond to mepolizumab in terms of corticosteroid tapering and eosinophil depletion to the same extent as corticosteroid-responsive F/P-negative patients with HES and a normal T-cell profile. Methods: Patients enrolled in the mepolizumab trial were evaluated for L-HES on the basis of T-cell phenotyping and T-cell receptor gene rearrangement patterns, and their serum thymus-and-activation-regulated chemokine (TARC) levels were measured. Response to treatment was compared in patient subgroups based on results of these analyses. Results: Lymphocytic variant HES was diagnosed in 13 of 63 patients with HES with complete T-cell assessments. The ability to taper corticosteroids on mepolizumab was similar in patients with L-HES and those with a normal T-cell profile, although a lower proportion of patients with L-HES maintained eosinophil levels below 600/μL. Increased serum TARC levels (>1000 pg/mL) had no significant impact on the ability to reduce corticosteroid doses, but a lower proportion of patients with elevated TARC achieved eosinophil control on mepolizumab. Conclusion: Mepolizumab is an effective corticosteroid-sparing agent for patients with L-HES. In some cases however, eosinophil levels remain above 600/μL, suggesting incomplete neutralization of overproduced IL-5 or involvement of other eosinophilopoietic factors. © 2010 American Academy of Allergy, Asthma & Immunology., SCOPUS: ar.j, info:eu-repo/semantics/published

"To the editor: Congratulations to Van Hulst et al for their article on the influence of interleukin (IL)-5 blockade on blood eosinophils in severe asthma [1]. In their discussion, the authors state that it is unclear if ‘increased stimulation-induced expression of Suppressor Of Cytokine Signaling-3 (SOCS3) in eosinophils in IL-5-depleted conditions has biological consequences’. However, their data can be linked to that of Seki et al. [2]and McDowell et al. [3] to speculate that the signal for stronger IL-33-mediated induction of SOCS3 becomes clinically relevant at the time of a mepolizumab-emergent asthma attack. [...]"