{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T19:12:13Z","timestamp":1760987533500,"version":"3.44.0"},"reference-count":13,"publisher":"The Pediatric Pharmacy Association","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021]]},"abstract":"\n OBJECTIVE<\/jats:title>\n To evaluate the impact of obesity on etanercept (ETN) drug exposure in children with juvenile idiopathic arthritis (JIA).<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n We conducted a pilot, cross-sectional, observational study in a real-world cohort of children with JIA receiving ETN as standard of care from a single center. We analyzed the relationship between body size and ETN plasma concentrations, adjusting for dosage. Body size was analyzed as a continuous measure using weight and body mass index (BMI) percentiles and categorically using BMI percentile classifications according to the CDC guidelines.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n We enrolled a total of 29 children. Each child provided one plasma sample for ETN concentration measurement, and all participants were receiving subcutaneous ETN dosed weekly. We observed that the ETN concentration normalized for dose decreased significantly as a function of weight (p = 0.004) and BMI percentile (p = 0.04). Similarly, we observed a progressive decline in mean and median dose-normalized concentrations across higher body size categories. Because of reaching maximum ETN dosage (50 mg), 7 of 8 children (87.5%) with obesity received a weight-based dosage < 0.8 mg\/kg\/dose.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n We found that higher body weight and BMI percentile are significantly and negatively associated with ETN drug serum concentration, accounting for differences in dosing. Our data suggest that children who are obese may be routinely under-dosed using current dosing strategies. Inadequate dosing may increase the risk for therapeutic failure and long-term morbidity in a developing child. As a result, characterizing adequate drug exposure in children of all sizes is an important step toward precision dosing.<\/jats:p>\n <\/jats:sec>","DOI":"10.5863\/1551-6776-26.8.809","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:52:24Z","timestamp":1636591944000},"page":"809-814","source":"Crossref","is-referenced-by-count":6,"title":["Low Etanercept Concentrations in Children With Obesity and Juvenile Idiopathic Arthritis"],"prefix":"10.5863","volume":"26","author":[{"given":"Stephen J.","family":"Balevic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara L.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan S.","family":"Funk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3883","reference":[{"issue":"11","key":"i1551-6776-26-8-809-b1","series-title":"N Engl J Med","first-page":"763","article-title":"Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group","volume":"342","year":"2000","unstructured":"Lovell\n DJ,\n \n \n Giannini\n EH,\n \n \n Reiff\n A,\n \n \n .\n\t\t\t\t\tEtanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group.\n\t\t\t\t\tN Engl J Med.\n\t\t\t\t\t2000;\n\t\t\t\t\t342(\n\t\t\t\t\t11):\n\t\t\t\t\t763\u2013\n\t\t\t\t\t769."},{"issue":"5","key":"i1551-6776-26-8-809-b2","series-title":"PLoS One","first-page":"e0195123","article-title":"Obesity and response to anti-tumor necrosis factor-alpha agents in patients with select immune-mediated inflammatory diseases: a systematic review and meta-analysis","volume":"13","year":"2018","unstructured":"Singh\n S,\n \n \n Facciorusso\n A,\n \n \n Singh\n AG,\n \n \n .\n\t\t\t\t\tObesity and response to anti-tumor necrosis factor-alpha agents in patients with select immune-mediated inflammatory diseases: a systematic review and meta-analysis.\n\t\t\t\t\tPLoS One.\n\t\t\t\t\t2018;\n\t\t\t\t\t13(\n\t\t\t\t\t5):\n\t\t\t\t\te0195123."},{"issue":"suppl 1","key":"i1551-6776-26-8-809-b3","series-title":"Dig Dis","first-page":"61","article-title":"The pharmacokinetics of biologics: a primer","volume":"33","year":"2015","unstructured":"Mould\n DR.\n \n \n The pharmacokinetics of biologics: a primer.\n\t\t\t\t\tDig Dis.\n\t\t\t\t\t2015;\n\t\t\t\t\t33(\n\t\t\t\t\tsuppl 1):\n\t\t\t\t\t61\u2013\n\t\t\t\t\t69."},{"issue":"4","key":"i1551-6776-26-8-809-b4","series-title":"Clin Pharmacol Ther","first-page":"348","article-title":"Population pharmacokinetic and pharmacodynamic modeling of etanercept using logistic regression analysis","volume":"73","year":"2003","unstructured":"Lee\n H,\n \n \n Kimko\n HC,\n \n \n Rogge\n M,\n \n \n .\n\t\t\t\t\tPopulation pharmacokinetic and pharmacodynamic modeling of etanercept using logistic regression analysis.\n\t\t\t\t\tClin Pharmacol Ther.\n\t\t\t\t\t2003;\n\t\t\t\t\t73(\n\t\t\t\t\t4):\n\t\t\t\t\t348\u2013\n\t\t\t\t\t365."},{"issue":"1","key":"i1551-6776-26-8-809-b5","series-title":"Pediatr Rheumatol Online J","first-page":"3","article-title":"Obesity and disease activity in juvenile idiopathic arthritis","volume":"10","year":"2012","unstructured":"Pelajo\n CF,\n \n \n Lopez-Benitez\n JM,\n \n \n Miller\n LC.\n \n \n Obesity and disease activity in juvenile idiopathic arthritis.\n\t\t\t\t\tPediatr Rheumatol Online J.\n\t\t\t\t\t2012;\n\t\t\t\t\t10(\n\t\t\t\t\t1):\n\t\t\t\t\t3."},{"issue":"1","key":"i1551-6776-26-8-809-b6","series-title":"Results from the Childhood Arthritis Prospective Study. Rheumatol (Oxford)","first-page":"116","article-title":"Disease activity and disability in children with juvenile idiopathic arthritis one year following presentation to paediatric rheumatology","volume":"49","year":"2010","unstructured":"Hyrich\n KL,\n \n \n Lal\n SD,\n \n \n Foster\n HE,\n \n \n .\n\t\t\t\t\tDisease activity and disability in children with juvenile idiopathic arthritis one year following presentation to paediatric rheumatology.\n\t\t\t\t\tResults from the Childhood Arthritis Prospective Study. Rheumatol (Oxford).\n\t\t\t\t\t2010;\n\t\t\t\t\t49(\n\t\t\t\t\t1):\n\t\t\t\t\t116\u2013\n\t\t\t\t\t122."},{"key":"i1551-6776-26-8-809-b7","unstructured":"CDC.\n \n About child & teen BMI.\n\t\t\t\t\tAccessed October 12, 2020. https:\/\/www.cdc.gov\/healthyweight\/assessing\/bmi\/childrens_bmi\/about_childrens_bmi.html","article-title":"About child & teen BMI"},{"issue":"3","key":"i1551-6776-26-8-809-b8","series-title":"J Clin Pharmacol","first-page":"246","article-title":"Population pharmacokinetic analysis and simulation of the time-concentration profile of etanercept in pediatric patients with juvenile rheumatoid arthritis","volume":"45","year":"2005","unstructured":"Yim\n DS,\n \n \n Zhou\n H,\n \n \n Buckwalter\n M,\n \n \n .\n\t\t\t\t\tPopulation pharmacokinetic analysis and simulation of the time-concentration profile of etanercept in pediatric patients with juvenile rheumatoid arthritis.\n\t\t\t\t\tJ Clin Pharmacol.\n\t\t\t\t\t2005;\n\t\t\t\t\t45(\n\t\t\t\t\t3):\n\t\t\t\t\t246\u2013\n\t\t\t\t\t256."},{"issue":"4","key":"i1551-6776-26-8-809-b9","series-title":"Br J Clin Pharmacol","first-page":"597","article-title":"What is the right dose for children?","volume":"70","year":"2010","unstructured":"Cella\n M,\n \n \n Knibbe\n C,\n \n \n Danhof\n M,\n \n \n Della Pasqua\n O.\n \n \n What is the right dose for children?\n \n Br J Clin Pharmacol\n .\n\t\t\t\t\t2010;\n\t\t\t\t\t70(\n\t\t\t\t\t4):\n\t\t\t\t\t597\u2013\n\t\t\t\t\t603."},{"key":"i1551-6776-26-8-809-b10","unstructured":"FDA.\n \n General clinical pharmacology considerations for pediatric studies for drugs and biological products.\n\t\t\t\t\tAccessed October 13, 2020. https:\/\/www.fda.gov\/downloads\/drugs\/guidances\/ucm425885.pdf","article-title":"General clinical pharmacology considerations for pediatric studies for drugs and biological products"},{"issue":"3","key":"i1551-6776-26-8-809-b11","series-title":"Ann Rheum Dis","first-page":"e16","article-title":"Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis","volume":"74","year":"2015","unstructured":"Chen\n DY,\n \n \n Chen\n YM,\n \n \n Tsai\n WC,\n \n \n .\n\t\t\t\t\tSignificant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis.\n\t\t\t\t\tAnn Rheum Dis.\n\t\t\t\t\t2015;\n\t\t\t\t\t74(\n\t\t\t\t\t3):\n\t\t\t\t\te16."},{"issue":"1","key":"i1551-6776-26-8-809-b12","series-title":"Ann Rheum Dis","first-page":"88","article-title":"Patients non-responding to etanercept obtain lower etanercept concentrations compared with responding patients","volume":"71","year":"2012","unstructured":"Jamnitski\n A,\n \n \n Krieckaert\n CL,\n \n \n Nurmohamed\n MT,\n \n \n .\n\t\t\t\t\tPatients non-responding to etanercept obtain lower etanercept concentrations compared with responding patients.\n\t\t\t\t\tAnn Rheum Dis.\n\t\t\t\t\t2012;\n\t\t\t\t\t71(\n\t\t\t\t\t1):\n\t\t\t\t\t88\u2013\n\t\t\t\t\t91."},{"key":"i1551-6776-26-8-809-b13","series-title":"Ann Rheum Dis","first-page":"1200","article-title":"Etanercept concentration in patients with juvenile idiopathic arthritis","volume":"79","year":"2020","unstructured":"K\u00e4rki\n J,\n \n \n Lev\u00e4lampi\n T,\n \n \n V\u00e4h\u00e4salo\n P,\n \n \n .\n\t\t\t\t\tEtanercept concentration in patients with juvenile idiopathic arthritis.\n\t\t\t\t\tAnn Rheum Dis.\n\t\t\t\t\t2020;\n\t\t\t\t\t79:\n\t\t\t\t\t1200\u2013\n\t\t\t\t\t1201."}],"container-title":["The Journal of Pediatric Pharmacology and Therapeutics"],"original-title":[],"link":[{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/26\/8\/article-p809.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/meridian.allenpress.com\/jppt\/article-pdf\/26\/8\/809\/3019021\/i1551-6776-26-8-809.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/26\/8\/article-p809.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/26\/8\/article-p809.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:44:32Z","timestamp":1747356272000},"score":1,"resource":{"primary":{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/26\/8\/article-p809.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":13,"journal-issue":{"issue":"8"},"URL":"https:\/\/doi.org\/10.5863\/1551-6776-26.8.809","relation":{},"ISSN":["1551-6776"],"issn-type":[{"type":"print","value":"1551-6776"}],"subject":[],"published":{"date-parts":[[2021]]}}}