{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T18:44:54Z","timestamp":1766169894345,"version":"3.48.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Investigator-Sponsored Studies (ISS) GSK"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Children with severe eosinophilic asthma are at an increased risk of severe exacerbations, medication side effects, impaired lung function, and significantly reduced quality of life. The advent of biologic agents aimed at eosinophilic pathways has significantly improved management options for patients with severe asthma.<\/jats:p>\n                    <jats:p>Mepolizumab, an anti-interleukin-5 monoclonal antibody, was approved in 2018 as an add-on maintenance treatment for patients with severe eosinophilic asthma aged \u22656 years of age. Mepolizumab\u2019s efficacy and safety is well documented in adults, but paediatric data remain limited. This real-world observational study will evaluate the long-term safety and efficacy of mepolizumab in children and adolescents, including those with comorbidities and on concomitant medications to provide a clearer picture of its performance in everyday clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Design: CASAM is an open label, multinational (Spain and United Kingdom), multicenter (15 Spanish and 6 UK public institutions) observational cohort study. Sample size: 150 paediatric patients on mepolizumab for SA between 6\u201317 years of age will be enrolled. Study Duration: Study will be conducted over 36 months (12 months pre mepolizumab initiation and 24 months after initiation). Data Collection: Pseudonymized data (prospective and retrospective) from medical charts will be collected and entered in the electronic case report forms (eCRFs) of the electronic data capture (EDC) system. Primary Outcome: To compare the rates of clinically significant asthma exacerbations in the pre-exposure and the 12-month post-exposure period with mepolizumab treatment. Protocol Version: CASAM Study_Protocol_V2.0_16th November 2023 KCH<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Registration details:<\/jats:title>\n                    <jats:p>The study is registered with ClinicalTrials.gov (NCT05139381), IRAS number 306475.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0335399","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T18:42:06Z","timestamp":1766169726000},"page":"e0335399","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protocol for an open labelled observational study in children &amp; adolescents with severe asthma with an eosinophilic phenotype treated with mepolizumab (CASAM)"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1610-0335","authenticated-orcid":true,"given":"Atul","family":"Gupta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1418-4563","authenticated-orcid":true,"given":"Ines","family":"de Mir Messa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-7613","authenticated-orcid":true,"given":"Jose","family":"Valverde-Molina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare S.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Moral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Torres Borrego","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharine","family":"Pike","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"D\u00edaz-Izquierdo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Mart\u00ednez-Ca\u00f1avate","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prasad","family":"Nagakumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Cook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Latika","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"On behalf of the CASAM Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"pone.0335399.ref001","unstructured":"(FDA) FaDA. Mepolizumab FDA 2023. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/125526Orig1s021,761122Orig1s011Corrected_lbl.pdf"},{"key":"pone.0335399.ref002","unstructured":"GINA. Global strategy for asthma management and prevention 2024. https:\/\/ginasthma.org\/2024-report\/"},{"key":"pone.0335399.ref003","unstructured":"Excellence NIoHac. Mepolizumab for treating severe eosinophilic asthma (NICE technology appraisal guidance Ta671). 2021. https:\/\/www.nice.org.uk\/guidance\/ta671"},{"key":"pone.0335399.ref004","unstructured":"WHO. Asthma. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/asthma#:~:text=Asthma%20affected%20an%20estimated%20262,help%20to%20reduce%20asthma%20symptoms"},{"issue":"5","key":"pone.0335399.ref005","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11882-015-0521-5","article-title":"Severe asthma in school-age children: evaluation and phenotypic advances","volume":"15","author":"A Coverstone","year":"2015","journal-title":"Curr Allergy Asthma Rep"},{"issue":"8","key":"pone.0335399.ref006","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/j.1398-9995.2008.01672.x","article-title":"Severe asthma in childhood: assessed in 10 year olds in a birth cohort study","volume":"63","author":"A Lang","year":"2008","journal-title":"Allergy"},{"issue":"8","key":"pone.0335399.ref007","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/j.rmed.2014.05.015","article-title":"Prevalence of severe childhood asthma according to the WHO","volume":"108","author":"B Nordlund","year":"2014","journal-title":"Respir Med"},{"issue":"3","key":"pone.0335399.ref008","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1164\/rccm.201904-0903SO","article-title":"Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management","volume":"201","author":"ER Bleecker","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"issue":"5","key":"pone.0335399.ref009","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1183\/13993003.00780-2015","article-title":"The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts","volume":"46","author":"L Fleming","year":"2015","journal-title":"Eur Respir J"},{"issue":"7","key":"pone.0335399.ref010","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/cea.13143","article-title":"Remodelling and inflammation in preschoolers with severe recurrent wheeze and asthma outcome at school age","volume":"48","author":"G Lezmi","year":"2018","journal-title":"Clin Exp Allergy"},{"issue":"1","key":"pone.0335399.ref011","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/apa.12046","article-title":"Clinical characteristics of eosinophilic and noneosinophilic asthma in children","volume":"102","author":"YJ Lee","year":"2013","journal-title":"Acta Paediatr"},{"issue":"5","key":"pone.0335399.ref012","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.jaci.2006.12.668","article-title":"Demographic and clinical characteristics of children and adolescents with severe or difficult-to-treat asthma","volume":"119","author":"BE Chipps","year":"2007","journal-title":"J Allergy Clin Immunol"},{"issue":"11","key":"pone.0335399.ref013","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1111\/j.1365-2222.2007.02839.x","article-title":"Eosinophilic airway inflammation and the prognosis of childhood asthma","volume":"37","author":"CJ Lovett","year":"2007","journal-title":"Clin Exp Allergy"},{"issue":"2","key":"pone.0335399.ref014","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1183\/09031936.00202013","article-title":"International ERS\/ATS guidelines on definition, evaluation and treatment of severe asthma","volume":"43","author":"KF Chung","year":"2014","journal-title":"Eur Respir J"},{"issue":"2","key":"pone.0335399.ref015","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/ACI.0b013e32835090ac","article-title":"Severe asthma in childhood: recent advances in phenotyping and pathogenesis","volume":"12","author":"AM Fitzpatrick","year":"2012","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"pone.0335399.ref016","unstructured":"CDC. Asthma-related Missed School Days among Children aged 5\u201317 Years. https:\/\/www.cdc.gov\/asthma\/asthma_stats\/missing_days.htm"},{"issue":"8","key":"pone.0335399.ref017","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1093\/jpepsy\/jst049","article-title":"Parenting stress among caregivers of children with chronic illness: a systematic review","volume":"38","author":"MK Cousino","year":"2013","journal-title":"J Pediatr Psychol"},{"key":"pone.0335399.ref018","unstructured":"EMA. Nucala. https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/nucala"},{"issue":"13","key":"pone.0335399.ref019","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1056\/NEJMoa1403291","article-title":"Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma","volume":"371","author":"EH Bel","year":"2014","journal-title":"N Engl J Med"},{"issue":"5","key":"pone.0335399.ref020","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S2213-2600(17)30125-X","article-title":"Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial","volume":"5","author":"GL Chupp","year":"2017","journal-title":"Lancet Respir Med"},{"issue":"9","key":"pone.0335399.ref021","doi-asserted-by":"crossref","DOI":"10.1016\/j.clinthera.2016.07.010","article-title":"Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study","volume":"38","author":"N Lugogo","year":"2016","journal-title":"Clin Ther"},{"issue":"13","key":"pone.0335399.ref022","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1056\/NEJMoa1403290","article-title":"Mepolizumab treatment in patients with severe eosinophilic asthma","volume":"371","author":"HG Ortega","year":"2014","journal-title":"N Engl J Med"},{"issue":"5","key":"pone.0335399.ref023","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaci.2018.09.033","article-title":"Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma","volume":"143","author":"S Khatri","year":"2019","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"pone.0335399.ref024","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.jaci.2013.11.026","article-title":"Outcomes after cessation of mepolizumab therapy in severe eosinophilic asthma: a 12-month follow-up analysis","volume":"133","author":"P Haldar","year":"2014","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"pone.0335399.ref025","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.jaci.2017.10.005","article-title":"Biomarkers for severe eosinophilic asthma","volume":"140","author":"SW Yancey","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"pone.0335399.ref026","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13223-019-0366-x","article-title":"Efficacy of add-on mepolizumab in adolescents with severe eosinophilic asthma","volume":"15","author":"SW Yancey","year":"2019","journal-title":"Allergy Asthma Clin Immunol"},{"issue":"9842","key":"pone.0335399.ref027","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0140-6736(12)60988-X","article-title":"Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial","volume":"380","author":"ID Pavord","year":"2012","journal-title":"Lancet"},{"issue":"10351","key":"pone.0335399.ref028","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/S0140-6736(22)01198-9","article-title":"Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial","volume":"400","author":"DJ Jackson","year":"2022","journal-title":"Lancet"},{"key":"pone.0335399.ref029","article-title":"Mepolizumab for severe eosinophilic asthma: a comparison of efficacy in children, adolescents, and adults","volume":"51","author":"A Gupta","year":"2018","journal-title":"Eur Respir J"},{"key":"pone.0335399.ref030","unstructured":"FDA. Drugs@FDA: FDA Approved Drug Products. https:\/\/www.fda.gov\/drugs\/development-approval-process-drugs\/drug-approvals-and-databases"},{"issue":"12","key":"pone.0335399.ref031","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1002\/ppul.24508","article-title":"Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma","volume":"54","author":"A Gupta","year":"2019","journal-title":"Pediatr Pulmonol"},{"issue":"5","key":"pone.0335399.ref032","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaci.2019.08.005","article-title":"Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype","volume":"144","author":"A Gupta","year":"2019","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"pone.0335399.ref033","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.jaci.2006.12.662","article-title":"Development and cross-sectional validation of the Childhood Asthma Control Test","volume":"119","author":"AH Liu","year":"2007","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"pone.0335399.ref034","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.jaci.2011.12.962","article-title":"Development and validation of the Composite Asthma Severity Index--an outcome measure for use in children and adolescents","volume":"129","author":"JJ Wildfire","year":"2012","journal-title":"J Allergy Clin Immunol"},{"issue":"5","key":"pone.0335399.ref035","doi-asserted-by":"crossref","first-page":"353","DOI":"10.2165\/00019053-199304050-00006","article-title":"The validity and reproducibility of a work productivity and activity impairment instrument","volume":"4","author":"MC Reilly","year":"1993","journal-title":"Pharmacoeconomics"},{"key":"pone.0335399.ref036","first-page":"1","article-title":"Mepolizumab in children and adolescents with severe eosinophilic asthma not eligible for omalizumab: a single center experience","author":"YT Lim","year":"2024","journal-title":"J Asthma"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T18:42:12Z","timestamp":1766169732000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335399"}},"subtitle":[],"editor":[{"given":"Stelios","family":"Loukides","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0335399","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]}}}