{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T02:53:09Z","timestamp":1793847189153,"version":"4.6.1"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,6,8]],"date-time":"2016-06-08T00:00:00Z","timestamp":1465344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The characterization of the pharmacokinetic (PK) and pharmacodynamic (PD) properties in pediatric patients is essential in supporting the recommended dosage of canakinumab in the relevant population. Here the PK and PD properties of canakinumab\u2014a monoclonal antibody\u2014in pediatric patients with systemic juvenile idiopathic arthritis (SJIA) are presented. Blood samples were obtained from 4 phase 2\/3 clinical studies in patients with SJIA. Canakinumab PK properties and total interleukin (IL)\u20101\u03b2 kinetic properties were characterized by a population\u2010based PK\u2010binding model. On administration, canakinumab increased total IL\u20101\u03b2 complex in SJIA patients. Canakinumab clearance and volume of distribution were not impacted by age in pediatric patients after correction for the patient's body weight. The estimated serum clearance of canakinumab was 0.106\u00a0\u00b1\u00a00.00689\u00a0L\/day, with a corresponding volume of distribution at steady state of 3.2\u00a0L and an estimated half\u2010life of 22\u00a0days, based on a model typical body weight of 33\u00a0kg. Body\u2010weight\u2013based dosing provided comparable canakinumab exposure across the age groups in patients 2 to &lt;20\u00a0years with SJIA. In younger children, a modest increase in the turnover rate of IL\u20101\u03b2 was observed. Compared to other indications, IL\u20101\u03b2 production rate was higher and clearance was slower in patients with SJIA. Low immunogenicity incidence of 3.1% was observed, and none of the patients had neutralizing antibodies. In conclusion, the PK\/PD findings further support dose selection of canakinumab in patients with SJIA.<\/jats:p>","DOI":"10.1002\/jcph.754","type":"journal-article","created":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T17:23:40Z","timestamp":1461777820000},"page":"1516-1527","source":"Crossref","is-referenced-by-count":46,"title":["Pharmacokinetics and Pharmacodynamics of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"56","author":[{"given":"Haiying","family":"Sun","sequence":"first","affiliation":[{"name":"Novartis Institutes for BioMedical Research  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linh M.","family":"Van","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Floch","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf R.","family":"Klein","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Abrams","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangadhar","family":"Sunkara","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,8]]},"reference":[{"issue":"2","key":"e_1_2_10_2_1","first-page":"229","article-title":"Biological therapies for the treatment of juvenile idiopathic arthritis: lessons from the adult and pediatric experiences","volume":"2","author":"Stoll ML","year":"2008","journal-title":"Biologics"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.9230"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.8975"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e3181cf0726"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1731"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00343-09"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-3081"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050473"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2143"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00046-9"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10688"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17401-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO;2-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3297"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.144063"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27600"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33342"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205099"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810787"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-12-153"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.162"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.170"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-012-0027-4"},{"issue":"2","key":"e_1_2_10_25_1","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty RE","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2004.12.016"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2165\/11599820-000000000-00000"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2008.09.020"},{"key":"e_1_2_10_29_1","unstructured":"European Medicines Agency (EMEA) Committee for Medicinal Products for Human Use (CHMP).Guideline on immunogenicity assessment of biotechnology\u2010derived therapeutic proteins. 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