scholarly journals Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial

2019 ◽  
Vol 5 (3) ◽  
pp. 00009-2019 ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Jonathan Corren ◽  
Elisabeth H. Bel ◽  
Jorge Maspero ◽  
Liam G. Heaney ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Asthma Control ◽  
Severe Asthma ◽  
Maintenance Phase ◽  
Phase Iii ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Link Type ◽  
Related Quality

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody approved in several countries for the add-on maintenance treatment of patients with severe eosinophilic asthma aged 12 years and older. In the 28-week Phase III ZONDA trial (ClinicalTrials.gov identifier: NCT02075255), benralizumab produced a median 75% reduction from baseline in oral corticosteroid (OCS) dosage (versus 25% for placebo) while maintaining asthma control for patients with OCS-dependent severe asthma. This manuscript presents the detailed protocol for the Phase IIIb PONENTE (ClinicalTrials.gov identifier: NCT03557307), a study that will build on the findings from ZONDA.As the largest steroid-sparing study undertaken in severe asthma, PONENTE has a faster steroid tapering schedule for prednisone dosages ≥7.5 mg·day−1 than previous studies, and it includes an evaluation of adrenal insufficiency and an algorithm to taper OCS dosage when prednisone dosage is ≤5 mg·day−1. It also has a longer maintenance phase to assess asthma control for up to 6 months after completion of OCS tapering.The two primary endpoints are whether patients achieve 100% reduction in daily OCS use and whether patients achieve 100% reduction in daily OCS or achieve OCS dosage ≤5 mg·day−1, if adrenal insufficiency prevented further reduction, both sustained over ≥4 weeks without worsening of asthma. Safety and change from baseline in health-related quality of life will also be assessed.PONENTE should provide valuable guidance for clinicians on tapering OCS dosage, including the management of adrenal insufficiency, following benralizumab initiation for the treatment of patients who are OCS-dependent with severe, uncontrolled eosinophilic asthma.

scholarly journals Severe eosinophilic bronchial asthma: new therapeutic options

2018 ◽  
pp. 44-52 ◽  
Author(s):  
N. M. Nenasheva
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Asthma ◽  
Bronchial Asthma ◽  
Biological Agents ◽  
Therapeutic Options ◽  
Clinical Use ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma

Eosinophilic asthma is a common phenotype of severe asthma, occurring in at least half of patients. In recent years, there have been significant changes in the approaches to the treatment of severe bronchial asthma and, above all, eosinophilic asthma. The article discusses the role of eosinophils in the pathogenesis of severe asthma, the detection of the phenotype of severe eosinophilic asthma, and modern approaches to targeting severe asthma with an eosinophilic phenotype using biological agents. A special emphasis is placed on preparations of monoclonal antibodies to interleukin-5, in particular, mepolizumab, recently approved for clinical use in our country.

scholarly journals Stopping versus continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study)

2021 ◽  
pp. 2100396
Author(s):  
Wendy C. Moore ◽  
Oliver Kornmann ◽  
Marc Humbert ◽  
Claude Poirier ◽  
Elisabeth H. Bel ◽  
...  
Keyword(s):  
Emergency Department ◽  
Asthma Control ◽  
Emergency Department Visit ◽  
Hazard Ratio ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Link Type ◽  
Clinically Significant

The long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use.COMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicenter study. Patients who had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692) and received continuous mepolizumab treatment for ≥3 years were randomised 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks. Primary endpoint: time to first clinically significant exacerbation; secondary endpoints: time to first exacerbation requiring hospitalisation/emergency department visit, time to decrease in asthma control (≥0.5-point increase in Asthma Control Questionnaire-5 score from COMET baseline), and blood eosinophil count ratio to COMET baseline. Safety was assessed.Patients stopping (n=151) versus continuing (n=144) mepolizumab had significantly shorter times to first clinically significant exacerbation (hazard ratio: 1.61 [95% confidence interval: 1.17,2.22]; p=0.004) and decrease in asthma control (hazard ratio: 1.52 [1.13,2.02]; p=0.005), and higher blood eosinophil counts at Week 52 (270 versus 40 cells·µL−1; ratio [stopping versus continuing]: 6.19 [4.89, 7.83]; p<0.001). Differences in efficacy outcomes between groups were observed when assessed from Week 12 (16 weeks after last mepolizumab dose). Exacerbations requiring hospitalisation/emergency department visit were rare. Adverse events in patients continuing mepolizumab were consistent with previous studies. For patients who stopped mepolizumab, the safety profile was consistent with other eosinophilic asthma populations.Patients who stopped mepolizumab had an increase in exacerbations and reduced asthma control versus those who continued.

scholarly journals Stratification of eosinophilic asthma patients treated with reslizumab and GINA Step 4 or 5 therapy

2017 ◽  
Vol 3 (3) ◽  
pp. 00004-2017 ◽  
Author(s):  
Guy Brusselle ◽  
Janice Canvin ◽  
Sivan Weiss ◽  
Shawn X. Sun ◽  
Roland Buhl
Keyword(s):  
Lung Function ◽  
Patient Reported Outcomes ◽  
Secondary Analysis ◽  
Forced Expiratory Volume ◽  
Phase Iii ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Patient Reported ◽  
Asthma Patients

Reslizumab, an anti-interleukin-5 monoclonal antibody, significantly reduces exacerbation frequency and improves lung function, asthma control and quality of life in adults with severe eosinophilic asthma, as demonstrated in Phase III studies.This secondary analysis assessed reslizumab's efficacy in patients receiving baseline treatment per Global Initiative for Asthma (GINA) Step 4 and Step 5 guidelines.Pooled data from duplicate, Phase III, reslizumab versus placebo studies in patients with severe eosinophilic asthma (blood eosinophils ≥400 cells·µL−1) were stratified by baseline therapy. Efficacy assessments were exacerbation rates and changes from baseline forced expiratory volume in 1 s (FEV1) and patient-reported outcomes.Of 953 patients, 69% (n=657) and 11% (n=106) were receiving Step 4 and Step 5 therapy, respectively. Compared with placebo, reslizumab reduced exacerbation rates by 53% (95% CI 0.36–0.62) and 72% (95% CI 0.15–0.52), in Step 4 and Step 5 groups respectively. By study end, reslizumab increased FEV1 in Step 4 and Step 5 groups by 103 mL (95% CI 52–154 mL) and 237 mL (95% CI 68–407 mL), respectively. Reslizumab also improved patient-reported outcomes compared with placebo in both groups.Reslizumab reduces exacerbation rates and improves lung function and patient-reported outcomes in patients with eosinophilic asthma receiving therapy per Steps 4 and 5 of the GINA guidelines.

scholarly journals The effectiveness of benralizumab in the treatment of the eosinophilic phenotype of severe asthma in real clinical practice

2021 ◽  
Vol 31 (5) ◽  
pp. 628-634
Author(s):  
Olga N. Titova ◽  
Natalia A. Kuzubova ◽  
Daria B. Sklyarova ◽  
Maria A. Petrova
Keyword(s):  
Clinical Practice ◽  
Asthma Control ◽  
Severe Asthma ◽  
Forced Expiratory Volume ◽  
Current Therapy ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Severe Eosinophilic Asthma ◽  
Night And Day ◽  
Real Clinical Practice

To evaluate the effectiveness of benralizumab in patients with the eosinophilic phenotype of severe asthma in real clinical practice after a year of therapy.Methods. During Benralizumab therapy, 13 patients with severe eosinophilic asthma (average age – 55.44 ± 7.18 years old) were examined twice: before the treatment and after 1 year of benralizumab therapy. The assessment included collection of complaints, medical history, current therapy, Asthma Control Questionnaire (ACQ-5) test, absolute blood count of eosinophils, spirometry.Results. All patients initially had pronounced eosinophilia of 577.5 ± 356.4 cells/μl. After 1 year of using benralizumab, the eosinophil count decreased by 96.15%. During therapy, the ACQ-5 index decreased from 1.63 ± 0.62 to 0.73 ± 0.41 in the study patients, which corresponded to the achievement of asthma control. The forced expiratory volume in 1 second (FEV1) increased by 23 %. The number of exacerbations decreased by 58.09%. 12 (92.31%) patients were on oral corticosteroids (OCS) (10 ± 2.17 mg of prednisolone daily) before benralizumab therapy. All subjects noted a decrease in night and day symptoms over time and were able to reduce the use of OCS. 5 (38.46%) patients achieved complete elimination of daily OCS use, 7 (53.84%) patients were able to reduce their daily OCS dose.Conclusion. Benralizumab therapy as an add-on maintenance treatment in patients with eosinophilic phenotype of severe asthma contributes to a significant decrease in peripheral blood eosinophils, which mediates an improvement in asthma control, an increase in FEV1, a reduction in the number of exacerbations, and a decrease in the need for the OCS usage. Careful monitoring of long-term adverse events is necessary during treatment with benralizumab.

scholarly journals Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Peter G. Gibson ◽  
Charlene M. Prazma ◽  
Geoffrey L. Chupp ◽  
Eric S. Bradford ◽  
Mark Forshag ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Asthma Control ◽  
Severe Asthma ◽  
Forced Expiratory Volume ◽  
Comorbid Conditions ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Severe Eosinophilic Asthma ◽  
St George's Respiratory Questionnaire ◽  
Clinically Significant

Abstract Background Comorbidities can complicate the management of severe asthma; therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities. Methods This was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA. Patients aged ≥ 12 years with severe eosinophilic asthma were randomized to: mepolizumab 750, 250, or 75 mg intravenously or placebo (DREAM); mepolizumab 75 mg intravenously or 100 mg subcutaneously or placebo (MENSA); or mepolizumab 100 mg subcutaneously or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA or 52 weeks in DREAM. In this analysis the primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints were Asthma Control Questionnaire-5 score, St George’s Respiratory Questionnaire total score, and pre-bronchodilator forced expiratory volume in 1 s at study end. Subgroups were based on comorbidities at baseline. Results Overall, 1878 patients received placebo (n = 689) or mepolizumab (n = 1189). Across all comorbidity subgroups mepolizumab reduced the rate of clinically significant exacerbations by 44–68% versus placebo, improved Asthma Control Questionnaire-5 score by 0.27–0.59 points, and improved St George’s Respiratory Questionnaire total score by 5.0–11.6 points. Pre-bronchodilator forced expiratory volume in 1 s was improved by 27.1–286.9 mL in all but one comorbidity subgroup, the diabetes mellitus subgroup. Conclusions Mepolizumab reduces exacerbations, and improves asthma control, health-related quality of life, and lung function in patients with severe eosinophilic asthma despite comorbid conditions, including upper respiratory conditions, psychopathologies, cardiovascular conditions, gastroesophageal reflux disease, diabetes mellitus, and obesity. Trial registration: https://clinicaltrials.gov/ DREAM, MEA112997/NCT01000506; MENSA, MEA115588/NCT01691521; SIRIUS, MEA115575/NCT01842607; MUSCA, 200862/NCT02281318.

scholarly journals Effectiveness of Benralizumab in Improving the Quality of Life of Severe Eosinophilic Asthmatic Patients: Our Real-Life Experience

2021 ◽  
Vol 12 ◽  
Author(s):  
Giulia Scioscia ◽  
Giovanna Elisiana Carpagnano ◽  
Carla Maria Irene Quarato ◽  
Donato Lacedonia ◽  
Sonia Santamaria ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Asthma Control ◽  
Severe Asthma ◽  
Life Experience ◽  
Real Life ◽  
Eosinophilic Inflammation ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma

Background: Severe eosinophilic asthma decreases lung function and causes worsen symptoms, often forcing recurrent maintenance corticosteroid use. The aim of our real-life study was to evaluate the effectiveness of an add-on treatment with benralizumab in patients with severe eosinophilic asthma, paying particular attention to the impact on their quality of life (QoL).Materials and methods: In this prospective study, 10 outpatients with severe eosinophilic asthma were added-on with benralizumab and followed-up in our severe asthma clinic after 12 and 24 weeks. At each patient visit, pre-bronchodilator FEV1 and inflammatory markers were recorded. Variations in asthma symptoms control and QoL perception was assessed by validated questionnaires.Results: All the subjects experienced a marked reduction of nocturnal and diurnal symptoms over time and were able to stop using OCS, as documented by the improvement in Asthma control test (ACT) and Asthma Control Questionnaire score. Similarly, we recorded a statistically significant increase in patient’s QoL perception in EQ-VAS, EQ-5D-3L and Asthma Quality of Life Questionnaire (AQLQ) assessment (p &lt; 0.05). Simultaneously we recorded a significant reduction in eosinophilic inflammation, an improvement in pre-bronchodilator FEV1. These results appear to be in line with those already obtained in the previous randomized controlled trials (RCTs).Conclusion: Our 24-weeks real life experience supports the effectiveness of an add-on treatment with benralizumab in reducing eosinophilic inflammation and OCS-use, increasing lung function and improving control of nocturnal and diurnal symptoms, as well as restoring severe asthma patients to a better QoL.

scholarly journals The effectiveness of Reslizumab in severe asthma treatment: a real-world experience

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
H. Ibrahim ◽  
R. O’Sullivan ◽  
D. Casey ◽  
J. Murphy ◽  
J. MacSharry ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Asthma Severity ◽  
Oral Steroid ◽  
Eosinophilic Asthma ◽  
Interleukin 5 ◽  
Severe Eosinophilic Asthma ◽  
Prednisolone Dose ◽  
Exacerbation Frequency ◽  
Efficacy Parameters

Abstract Background Increased numbers of blood and sputum eosinophils are associated with higher exacerbation frequency and increased asthma severity. In clinical trials, targeting Interleukin-5 has been shown to be a useful therapeutic strategy for patients with severe eosinophilic asthma. Methods Twenty-six patients have been commenced on Reslizumab in our institution since early 2017. Safety and clinical efficacy parameters were recorded at regular intervals. Results Mean ACQ-6 score at the start of treatment was 3.5. The average number of exacerbations in the year preceding treatment was 8.3 per person. 30% of patients had been admitted to hospital at least once over the 12 months preceding therapy. 54% of our patients were on long term oral steroid. Our data showed sustained improvement of Asthma control (Mean improvement in ACQ-6 was 1.7 at 1 year, and 2.0 at 2 years, P = 0.0001). Of the patients who were on long term systemic steroids, 35.7% discontinued steroids completely, with a mean reduction of prednisolone dose of 5.2 mg at 1 year. There was a 79% reduction in the annual exacerbation frequency at 1 year, and 88% at 2 years (P = < 0.0001). Modest, albeit statistically significant increases in creatine kinase which seemed to plateau by 1 year were noted. Conclusions Overall, Reslizumab was well tolerated with discontinuation of treatment due to side effects recorded in only one patient. Our data confirm the utility of anti-IL5 therapy in a carefully selected phenotype of severe asthma with evidence of eosinophilic airway inflammation.

scholarly journals Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Catherine Lemiere ◽  
Camille Taillé ◽  
Jason Kihyuk Lee ◽  
Steven G. Smith ◽  
Stephen Mallett ◽  
...  
Keyword(s):  
Lung Function ◽  
Asthma Control ◽  
Clinical Characteristics ◽  
Meta Analysis ◽  
Phase Iii ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Clinically Significant ◽  
Post Hoc ◽  
Airway Reversibility

Abstract Background Severe asthma is associated with a broad range of phenotypes and clinical characteristics. This analysis assessed whether select baseline patient characteristics could prognosticate mepolizumab efficacy in severe eosinophilic asthma. Methods This was a post hoc meta-analysis of data from the Phase III MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862) studies. Patients aged ≥ 12 years with severe eosinophilic asthma and a history of exacerbations were randomised to receive placebo (MENSA/MUSCA), mepolizumab 75 mg intravenously (MENSA) or 100 mg subcutaneously (SC) (MENSA/MUSCA) every 4 weeks for 32 (MENSA) or 24 (MUSCA) weeks. The primary endpoint was the annual rate of clinically significant exacerbations; other outcomes included the proportion of patients with no exacerbations and changes from baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV1), St George’s Respiratory Questionnaire (SGRQ) total score and Asthma Control Questionnaire (ACQ)-5 score. Analyses were performed by baseline age of asthma onset (< 18 years; 18–40 years; ≥ 40 years); lung function (% predicted FEV1 ≤ 60; 60–80; > 80); airway reversibility (reversible [≥ 12% change in FEV1]; non-reversible [< 12% change in FEV1]); perennial and/or seasonal allergen sensitivity (yes/no); asthma control (uncontrolled [ACQ-5 score ≥ 1.5]; partial/complete control [ACQ-5 score < 1.5]). Results Overall, 936 patients received mepolizumab 100 mg SC or placebo. Across age at asthma onset, lung function and airway reversibility subgroups, mepolizumab reduced the rate of clinically significant exacerbations by 49–63% versus placebo. Improvements in lung function, SGRQ total score and ACQ-5 score were also seen with mepolizumab versus placebo across most age and lung function subgroups. Clinically significant exacerbations were reduced with mepolizumab versus placebo irrespective of season or allergen sensitivity; SGRQ total and ACQ-5 scores were generally improved across seasons. Conclusions Mepolizumab efficacy was consistent for patients with varying age at asthma onset, lung function, airway reversibility and allergen sensitivities at baseline. Our results indicate that mepolizumab is likely to be beneficial for patients with severe eosinophilic asthma with a broad range of baseline clinical characteristics; large-scale real-world studies are needed to confirm the external validity of these findings. Trial registration Post hoc meta-analysis of data from MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862)

scholarly journals Clinical and Economic Consequences of Switching From Omalizumab to Mepolizumab in Uncontrolled Severe Eosinophilic Asthma: an Observational Retrospective Study

2020 ◽  
Author(s):  
Giovanna Elisiana Carpagnano ◽  
Emanuela Resta ◽  
Massimiliano Povero ◽  
Corrado Pelaia ◽  
Mariella D'Amato ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Asthma Control ◽  
Exhaled Nitric Oxide ◽  
Blood Eosinophil ◽  
Fractional Exhaled Nitric Oxide ◽  
Eosinophilic Asthma ◽  
Exacerbation Rate ◽  
Serum Ige ◽  
Severe Eosinophilic Asthma ◽  
Oral Corticosteroids

Abstract Background: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids, which worsen patients’ health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab to mepolizumab in patients eligible for both biologics, but not optimally controlled by omalizumab.Methods: We retrospectively enrolled uncontrolled severe asthmatic patients, referred to seven asthma clinics in Italy, who switched from omalizumab to mepolizumab during the last two years. Clinical, functional, and laboratory information included blood eosinophil count, asthma control test, spirometry, serum IgE, fractional exhaled nitric oxide, oral corticosteroids intake, use of controller and rescue drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-mepolizumab 12-month standardized total cost per patient was calculated.Results: 33 patients were enrolled: 5 males and 28 females, mean age 57 years, mean disease onset 24 years. At omalizumab discontinuation, 88% were oral corticosteroids-dependent with annual mean rate of 4.0 clinically significant exacerbations, 0.30 exacerbations needing emergency room visits or hospitalization; absenteeism due to disease was 10.4 days per patient. Switch to mepolizumab improved all clinical outcomes, reducing total exacerbation rate (RR = 0.06, 95% CI 0.03 to 0.14), oral corticosteroids -dependent patients (OR = 0.02, 95% CI 0.005 to 0.08), and the number of lost working days because of uncontrolled disease (Δ = -7.9, 95% CI -11.2 to -4.6). Pulmonary function improved, as well as serum IgE, fractional exhaled nitric oxide and eosinophils decreased. Mean annual costs were € 12,239 for omalizumab and € 12,639 for mepolizumab (Δ = € 400, 95% CI -1,588 to 2,389); the increment due to drug therapy (+ € 1,581) was almost offset by savings regarding all other cost items (- € 1,181). Conclusions: Patients with severe eosinophilic asthma, not controlled by omalizumab, experienced comprehensive benefits in asthma control by switching to mepolizumab. These relevant improvements were burdened by only very slight increases in economic costs.

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