Dataset Information

Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma.

ABSTRACT: OBJECTIVES:There are no published reports for anti-interleukin-5 therapy in children <12 years with asthma. The primary objective of this study was to characterize the pharmacokinetics and pharmacodynamics of mepolizumab following subcutaneous (SC) administration in children 6 to 11 years-of-age with severe eosinophilic asthma. HYPOTHESIS:Mepolizumab SC pharmacokinetics and pharmacodynamics in children with severe eosinophilic asthma are comparable with adults. STUDY DESIGN:Multinational, nonrandomised, open-label (NCT02377427). PATIENT SELECTION:Children 6 to 11 years-of-age with severe eosinophilic asthma (blood eosinophil count ?150?cells/µL at screening or ?300?cells/µL <12 months of screening) and ?2 exacerbations in the prior year. METHODOLOGY:Children received mepolizumab SC 40?mg (bodyweight <40?kg) or 100?mg (?40?kg) every 4 weeks for 12 weeks. RESULTS:Thirty-six children received mepolizumab (40?mg, n?=?26; 100?mg, n?=?10). Mepolizumab exposures were higher and apparent clearance lower than predicted based on prior existing data. Derived mepolizumab exposures normalized to mean bodyweight for the 40?mg and 100?mg dose groups were 454??g?*?day/mL and 675??g?*?day/mL, respectively. At week 12, blood eosinophils were reduced by 89% and 83% from baseline to 42 and 55?cells/µL, respectively. Mepolizumab was well tolerated; no new safety signals were observed compared with previous adult/adolescent studies. CONCLUSION:In children 6 to 11 years-of-age with severe eosinophilic asthma, mepolizumab SC 40 or 100?mg provided bodyweight-adjusted drug exposure within twofold of target adult exposure as well as marked reductions to blood eosinophil counts similar to adults, and although not designed to evaluate efficacy outcomes, demonstrated a positive clinical profile.

SUBMITTER: Gupta A

PROVIDER: S-EPMC6972599 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma.

Gupta Atul A Pouliquen Isabelle I Austin Daren D Price Robert G RG Kempsford Rodger R Steinfeld Jonathan J Bradford Eric S ES Yancey Steven W SW

Pediatric pulmonology 20190909 12

<h4>Objectives</h4>There are no published reports for anti-interleukin-5 therapy in children <12 years with asthma. The primary objective of this study was to characterize the pharmacokinetics and pharmacodynamics of mepolizumab following subcutaneous (SC) administration in children 6 to 11 years-of-age with severe eosinophilic asthma.<h4>Hypothesis</h4>Mepolizumab SC pharmacokinetics and pharmacodynamics in children with severe eosinophilic asthma are comparable with adults.<h4>Study design</h4 ...[more]

PMID: 31502421

Similar Datasets

Project description:PurposeImproved understanding of characteristics that may influence treatment response across phenotypes may help guide treatment decisions.Patients and methodsThis was a post hoc analysis of MENSA, a multicenter, randomized, double-blind, placebo-controlled trial (NCT01691521). Patients aged ≥12 years with severe eosinophilic asthma received mepolizumab (75 mg intravenously or 100 mg subcutaneously) or placebo, plus standard of care, every 4 weeks for 32 weeks. Outcomes assessed were the annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire (ACQ)-5 score. Subgroup analyses were performed by baseline blood eosinophil count (<150, ≥150-300, ≥300 cells/μL) within atopic subgroups (non-atopic [specific immunoglobulin E <0.35 kU/L], atopic [≥0.35-17.5 kU/L], strongly atopic [>17.5 kU/L]), and by house dust mite (HDM) sensitivity.ResultsOf 576 patients analyzed, 272 were non-atopic, 181 were atopic and 94 were strongly atopic; 29 had missing atopy data. In patients with blood eosinophil counts ≥300 cells/µL, mepolizumab versus placebo reduced clinically significant exacerbations by 74%, 43% and 25% in the non-atopic, atopic and strongly atopic subgroups. Similar reductions were observed in all atopic subgroups in other blood eosinophil count categories where there were sufficient patient numbers for analysis, except for non-atopic patients with baseline blood eosinophil counts of <150 cells/μL. Improvements in ACQ-5 scores of -0.75, -0.73 and -0.78 with mepolizumab versus placebo were observed in non-atopic, atopic and strongly atopic patients with blood eosinophil counts ≥300 cells/µL; consistent improvements in ACQ-5 were not observed in patients with blood eosinophil counts <150 or ≥150-300 cells/μL. Reductions in clinically significant exacerbations with mepolizumab versus placebo were also observed irrespective of sensitivity to HDMs.ConclusionMepolizumab was associated with a trend for reductions in clinically significant exacerbations and improved asthma control versus placebo in patients with severe eosinophilic asthma, irrespective of atopic status or HDM sensitivity.

Project description:Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources. Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations.We conducted a randomized, double-blind, placebo-controlled, parallel-group study of 61 subjects who had refractory eosinophilic asthma and a history of recurrent severe exacerbations. Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year. The primary outcome measure was the number of severe exacerbations per subject during the 50-week treatment phase. Secondary outcomes included a change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, in which scores range from 1 to 7, with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinically important), forced expiratory volume in 1 second (FEV(1)) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum.Mepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks (2.0 vs. 3.4 mean exacerbations per subject; relative risk, 0.57; 95% confidence interval [CI], 0.32 to 0.92; P=0.02) and with a significant improvement in the score on the AQLQ (mean increase from baseline, 0.55 vs. 0.19; mean difference between groups, 0.35; 95% CI, 0.08 to 0.62; P=0.02). Mepolizumab significantly lowered eosinophil counts in the blood (P<0.001) and sputum (P=0.002). There were no significant differences between the groups with respect to symptoms, FEV(1) after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma.Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma. The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population. (Current Controlled Trials number, ISRCTN75169762.)

Dataset Information

Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma.

Publications

Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets