{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:36:30Z","timestamp":1791466590876,"version":"4.3.4"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T00:00:00Z","timestamp":1659225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100017759","name":"Childhood Arthritis and Rheumatology Research Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017759","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp; Research"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To describe high\u2010dose biologic use when treating juvenile idiopathic arthritis (JIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry and treated with a biologic after enrollment were eligible. We described the frequency of high\u2010dose biologic use and characteristics of patients receiving high\u2010dose biologics. We used regression modeling to compare 6\u2010month outcomes (using disease activity measures) between those who increased their biologic from standard to high dose (high\u2010dose group) to those who initiated and remained on standard dosing (no\u2010change group), and to those who switched biologic agents (biologic\u2010switch group). We also compared serious adverse events (SAEs) between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 5,352 patients with JIA were treated with biologics following enrollment; 1,080 (20%) had ever received a high\u2010dose biologic. There were no significant differences in outcomes between the high\u2010dose group and the biologic\u2010switch group; both improved disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score 10 (\u20133.53 and \u20133.95, respectively; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.68). Although the SAE rates in the high\u2010dose group and the biologic\u2010switch group were numerically higher than the no\u2010change group, the event rates were similar, and neither rate was significantly higher than in the no\u2010change group (unadjusted incident rate ratio 2.5 [95% confidence interval (95% CI) 0.7\u20138.5] and 1.8 [95% CI 0.7\u20134.6], respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Dosing escalation appears to be a reasonable choice to improve disease control, but large, prospective, randomized studies evaluating specific biologic agents are needed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.24727","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T01:08:15Z","timestamp":1623632895000},"page":"1770-1779","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effectiveness and Safety of High\u2010Dose Biologics in Juvenile Idiopathic Arthritis in the Childhood Arthritis and Rheumatology Research Alliance"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5451-1936","authenticated-orcid":false,"given":"Colleen K.","family":"Correll","sequence":"first","affiliation":[{"name":"University of Minnesota  Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Shrader","sequence":"additional","affiliation":[{"name":"Duke University  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Dennos","sequence":"additional","affiliation":[{"name":"Duke University  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Phillips","sequence":"additional","affiliation":[{"name":"Duke University  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-9709","authenticated-orcid":false,"given":"Natalie J.","family":"Shiff","sequence":"additional","affiliation":[{"name":"University of Saskatchewan  Saskatoon Saskatchewan Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6638-8405","authenticated-orcid":false,"given":"Ruud H. J.","family":"Verstegen","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children and University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Beukelman","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Childhood Arthritis and Rheumatology Research Alliance Registry Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,31]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23870"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60244-4"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40885"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3890-4"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.130133"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27541"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.121098"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2006.01.005"},{"key":"e_1_2_6_10_1","first-page":"1677","article-title":"Safety and efficacy of high dose etanercept in treatment of juvenile rheumatoid arthritis","volume":"28","author":"Takei S","year":"2001","journal-title":"J Rheumatol"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-017-0160-6"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504370"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.106781"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.11041.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000715"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.013052"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30128"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21625"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez030"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez285"},{"key":"e_1_2_6_21_1","first-page":"737","article-title":"Burden of dose escalation with tumour necrosis factor inhibitors in rheumatoid arthritis: a systematic review of frequency and costs","volume":"33","author":"Moots RJ","year":"2015","journal-title":"Clin Exp Rheumatol"}],"container-title":["Arthritis Care &amp; Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr.24727","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acr.24727","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr.24727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T16:10:31Z","timestamp":1759421431000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/acr.24727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,31]]},"references-count":20,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/acr.24727"],"URL":"https:\/\/doi.org\/10.1002\/acr.24727","archive":["Portico"],"relation":{},"ISSN":["2151-464X","2151-4658"],"issn-type":[{"value":"2151-464X","type":"print"},{"value":"2151-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,31]]},"assertion":[{"value":"2021-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}