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- Bjermer, Leif, et al.
(författare)
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Reslizumab for Inadequately Controlled Asthma with Elevated Blood Eosinophil Levels : a Randomized Phase 3 Study
- 2016
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Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 150:4, s. 789-798
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This phase 3 study further characterizes the efficacy and safety of reslizumab (a humanized anti-interleukin-5 monoclonal antibody) in patients aged 12-75 years with asthma inadequately controlled by at least a medium-dose inhaled corticosteroid, and blood eosinophils ≥400cells/μL.METHODS: Patients were randomized to receive reslizumab 0.3 or 3.0mg/kg or placebo once/every 4 weeks/16 weeks. Primary endpoint was change from baseline in pre-bronchodilator forced expiratory volume in 1 sec (FEV1) over 16 weeks. Secondary endpoints included forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF25-75%), patient-reported control of asthma symptoms, short-acting beta agonist (SABA) use, blood eosinophil levels, and safety.RESULTS: Reslizumab significantly improved FEV1 (difference vs placebo [reslizumab 0.3 and 3.0mg/kg]:115mL[95% CI 16-215; P= .0237] and 160mL[95% CI 60-259; P= .0018]). Clinically meaningful increases in FVC (130mL) and FEF25-75% (233mL/s) were observed with reslizumab 3.0mg/kg. Reslizumab improved Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) versus placebo (greater effects seen with 3.0mg/kg; P<0.05). The minimally important difference was reached for AQLQ (reslizumab 3.0mg/kg) but not ACQ. Asthma Symptom Utility Index and SABA use were improved with reslizumab. The most common adverse events were asthma worsening, headache, and nasopharyngitis; most were mild-to-moderate in severity.CONCLUSIONS: Reslizumab improved lung function, asthma control and symptoms, and quality of life, and was well tolerated in patients with inadequately controlled asthma (despite standard therapy), and elevated blood eosinophils. Overall, the 3.0mg/kg dose of reslizumab provided greater improvements in asthma outcomes (vs 0.3mg/kg), with comparable safety.
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| 2. |
- Heaney, Liam G., et al.
(författare)
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Eosinophilic and Noneosinophilic Asthma : An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort
- 2021
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Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 160:3, s. 814-830
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Tidskriftsartikel (refereegranskat)abstract
- Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.
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| 3. |
- Murphy, Kevin, et al.
(författare)
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Long-term Safety and Efficacy of Reslizumab in Patients with Eosinophilic Asthma
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology: In Practice. - : Elsevier BV. - 2213-2198. ; 5:6, s. 3-1581
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Tidskriftsartikel (refereegranskat)abstract
- Background In placebo-controlled trials, reslizumab, an anti-IL-5 monoclonal antibody, significantly reduced asthma exacerbations and improved lung function and asthma control in patients with eosinophilic asthma. Objective This open-label extension study evaluated safety and efficacy of reslizumab for up to 24 months. Methods After participation in 1 of 3 placebo-controlled, phase III trials in moderate-to-severe eosinophilic asthma, patients received reslizumab 3.0 mg/kg intravenously every 4 weeks for up to 24 months. Adverse events (AEs), lung function, and patient-reported asthma control were evaluated. Results In the open-label extension, 1,051 patients received ≥1 reslizumab dose (480 reslizumab-naïve, 571 reslizumab-experienced); median (range) exposure was 319 (36-840) and 343 (36-863) days in reslizumab-naïve and reslizumab-experienced patients, respectively. Continuous exposure, including during the placebo-controlled studies, was ≥12 months for 740 patients and ≥24 months for 249 patients. The most common AEs were worsening of asthma and nasopharyngitis. Serious AEs affected 78 of 1,051 (7%) patients; 18 of 1,051 (2%) discontinued treatment because of AEs; and there were 3 deaths (all non-treatment-related). Fifteen adult patients (15 of 1,023; 1%) had malignancies of diverse tissue types. Reslizumab-experienced patients maintained improved lung function and asthma control; reslizumab-naïve patients had improvements in these measures throughout open-label treatment. Blood eosinophil counts appeared to be returning to baseline after reslizumab discontinuation. Conclusions In patients with moderate-to-severe eosinophilic asthma, intravenous reslizumab 3.0 mg/kg displays favorable long-term safety and sustained long-term efficacy. Initial improvements in lung function and asthma control were maintained for up to 2 years. These findings substantially add to our understanding of the long-term safety and efficacy of anti-IL-5 strategies.
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