{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:20:13Z","timestamp":1790277613730,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:00:00Z","timestamp":1567987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002066","name":"GlaxoSmithKline foundation","doi-asserted-by":"publisher","award":["200363"],"award-info":[{"award-number":["200363"]}],"id":[{"id":"10.13039\/501100002066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>There are no published reports for anti\u2010interleukin\u20105 therapy in children &lt;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\u2010of\u2010age with severe eosinophilic asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Hypothesis<\/jats:title><jats:p>Mepolizumab SC pharmacokinetics and pharmacodynamics in children with severe eosinophilic asthma are comparable with adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Multinational, nonrandomised, open\u2010label (NCT02377427).<\/jats:p><\/jats:sec><jats:sec><jats:title>Patient Selection<\/jats:title><jats:p>Children 6 to 11 years\u2010of\u2010age with severe eosinophilic asthma (blood eosinophil count \u2265150\u2009cells\/\u00b5L at screening or \u2265300\u2009cells\/\u00b5L &lt;12 months of screening) and \u22652 exacerbations in the prior year.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Children received mepolizumab SC 40\u2009mg (bodyweight &lt;40\u2009kg) or 100\u2009mg (\u226540\u2009kg) every 4 weeks for 12 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010six children received mepolizumab (40\u2009mg, <jats:italic>n<\/jats:italic>\u2009=\u200926; 100\u2009mg, <jats:italic>n<\/jats:italic>\u2009=\u200910). 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\u2009mg and 100\u2009mg dose groups were 454\u2009\u03bcg\u2009*\u2009day\/mL and 675\u2009\u03bcg\u2009*\u2009day\/mL, respectively. At week 12, blood eosinophils were reduced by 89% and 83% from baseline to 42 and 55\u2009cells\/\u00b5L, respectively. Mepolizumab was well tolerated; no new safety signals were observed compared with previous adult\/adolescent studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In children 6 to 11 years\u2010of\u2010age with severe eosinophilic asthma, mepolizumab SC 40 or 100\u2009mg provided bodyweight\u2010adjusted 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.24508","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T05:29:31Z","timestamp":1568093371000},"page":"1957-1967","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma"],"prefix":"10.1002","volume":"54","author":[{"given":"Atul","family":"Gupta","sequence":"first","affiliation":[{"name":"King's College Hospital NHS Foundation Trust King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Pouliquen","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modelling and Simulation GSK Uxbridge Middlesex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daren","family":"Austin","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modelling and Simulation GSK Uxbridge Middlesex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Price","sequence":"additional","affiliation":[{"name":"Clinical Statistics GSK Stevenage Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodger","family":"Kempsford","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modelling and Simulation, R&amp;D Medicines Research Centre GSK Stevenage Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3947-0523","authenticated-orcid":false,"given":"Jonathan","family":"Steinfeld","sequence":"additional","affiliation":[{"name":"Respiratory TAU &amp; Flexible Discovery Unit GSK Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric S.","family":"Bradford","sequence":"additional","affiliation":[{"name":"Respiratory Therapeutic Area GSK Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Yancey","sequence":"additional","affiliation":[{"name":"Respiratory Therapeutic Area GSK Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"e_1_2_9_1_2_1","unstructured":"World Health Organization. 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