{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:21:42Z","timestamp":1792012902882,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The selective T\u2010cell costimulation modulator abatacept is approved for treatment of adult rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA; 6\u201017 years [intravenous] and 2\u201017 years [subcutaneous]). An extrapolation approach was taken to determine subcutaneous weight\u2010tiered doses of abatacept to evaluate in patients with pJIA. Population pharmacokinetic (PPK) and exposure\u2010response (E\u2010R) analyses were conducted to determine whether the weight\u2010tiered subcutaneous regimen provides near\u2010maximal efficacy and is therapeutically comparable to the intravenous regimen in patients with pJIA aged 2\u201017 years. Combined study data from intravenous or subcutaneous abatacept were used to assess clinically relevant exposure outcomes. The PPK model was developed with data from 13 phase 2\/3 studies in RA and pJIA; the E\u2010R model for the American College of Rheumatology pediatric scores (JIA\u2010ACR 30\/50\/70\/100 responses) in month 4 was developed with data from 2 phase 3 pJIA studies. Predefined covariates were investigated in both analyses. PPK model\u2010predicted exposures were steady\u2010state peak, trough (C<jats:sub>minss<\/jats:sub>), and time\u2010averaged concentrations. Abatacept PK was characterized by a linear 2\u2010compartment model (zero\u2010order intravenous infusion, first\u2010order subcutaneous absorption, first\u2010order elimination); body weight was the only clinically relevant covariate. C<jats:sub>minss<\/jats:sub> was the best exposure predictor for the JIA\u2010ACR response: log odds for response increased in proportion to log\u2010transformed C<jats:sub>minss<\/jats:sub>; JIA\u2010ACR30 approached a plateau when C<jats:sub>minss<\/jats:sub> \u2265 10 \u03bcg\/mL. The PPK and E\u2010R analyses demonstrated that the weight\u2010tiered subcutaneous and intravenous abatacept dosing regimens provide near\u2010maximal efficacy and are clinically comparable across children with pJIA who are &gt;\u20092 years old.<\/jats:p>","DOI":"10.1002\/jcph.1797","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T16:28:05Z","timestamp":1607358485000},"page":"688-699","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Model\u2010Based Selection and Recommendation for Subcutaneous Abatacept Dose in Patients With Polyarticular Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"61","author":[{"given":"Yash","family":"Gandhi","sequence":"first","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Passarell","sequence":"additional","affiliation":[{"name":"Cognigen Corporation  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Roy","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindu","family":"Murthy","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-017-0160-6"},{"issue":"13","key":"e_1_2_12_3_1","first-page":"1","article-title":"Treatment of juvenile idiopathic arthritis: a revolution in care","volume":"12","author":"Stoll ML","year":"2014","journal-title":"Pediatr Rheumatol Online J"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-008-0964-3"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30463"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.130112"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/14397595.2014.881954"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203843"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37711"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.120906"},{"issue":"4","key":"e_1_2_12_11_1","first-page":"553","article-title":"Long\u2010term safety and efficacy of abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: a 7\u2010year extended study","volume":"32","author":"Westhovens R","year":"2014","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39234"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60998-8"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27431"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40466"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1308"},{"key":"e_1_2_12_17_1","unstructured":"Bristol Myers Squibb. Orencia (abatacept) summary of product characteristics: EMC.https:\/\/www.medicines.org.uk\/emc\/medicine\/27216\/SPC\/ORENCIA+125+mg+solution+for+injection+(pre-filled+syringe). Published 2017. Accessed November 13 2020."},{"key":"e_1_2_12_18_1","unstructured":"Bristol Myers Squibb. Orencia (abatacept) prescribing information: Bristol\u2010Myers Squibb.http:\/\/packageinserts.bms.com\/pi\/pi_orencia.pdf. Published 2019. Accessed November 13 2020."},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.160904.C1"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(02)17635-1"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004271945"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-018-0261-x"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-012-9367-0"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260327"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.11.5512"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.170"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1797","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1797","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1797","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T03:26:07Z","timestamp":1693625167000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,18]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/jcph.1797"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1797","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,18]]},"assertion":[{"value":"2020-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}