{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:43:45Z","timestamp":1790711025169,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T00:00:00Z","timestamp":1409011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["NO1 AR 700015"],"award-info":[{"award-number":["NO1 AR 700015"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the efficacy and safety of rilonacept, an interleukin\u20101 inhibitor, in a randomized, double\u2010blind, placebo\u2010controlled trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An initial 4\u2010week double\u2010blind placebo phase was incorporated into a 24\u2010week randomized multicenter design, followed by an open\u2010label phase. Seventy\u2010one children who had active arthritis in \u22652 joints were randomized (1:1) to the 2 arms of the study. Patients in the rilonacept arm received rilonacept (loading dose 4.4 mg\/kg followed by 2.2 mg\/kg weekly, subcutaneously) beginning on day 0. Patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary end point was time to response, using the adapted American College of Rheumatology Pediatric 30 criteria coupled with the absence of fever and taper of the dosage of systemic corticosteroids, using prespecified criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The time to response was shorter in the rilonacept arm than in the placebo arm (\u03c7<jats:sup>2<\/jats:sup> = 7.235, <jats:italic>P<\/jats:italic> = 0.007). The secondary analysis, which used the same response criteria, showed that 20 (57%) of 35 patients in the rilonacept arm had a response at week 4 compared with 9 (27%) of 33 patients in the placebo arm (<jats:italic>P<\/jats:italic> = 0.016). Exacerbation of systemic juvenile idiopathic arthritis (JIA) was the most common severe adverse event. More patients in the rilonacept arm had elevated liver transaminase levels (including levels more than 3 times the upper limit of normal) compared with those in the placebo arm. Adverse events were similar in the 2 arms of the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Rilonacept was generally well tolerated and demonstrated efficacy in active systemic JIA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38699","type":"journal-article","created":{"date-parts":[[2014,5,16]],"date-time":"2014-05-16T11:29:09Z","timestamp":1400239749000},"page":"2570-2579","source":"Crossref","is-referenced-by-count":154,"title":["Randomized, Double\u2010Blind, Placebo\u2010Controlled Trial of the Efficacy and Safety of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"66","author":[{"given":"Norman T.","family":"Ilowite","sequence":"first","affiliation":[{"name":"Children's Hospital at Montefiore, Albert Einstein College of Medicine Bronx New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi","family":"Prather","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliya","family":"Lokhnygina","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Schanberg","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Elder","sequence":"additional","affiliation":[{"name":"University of Florida Gainesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Milojevic","sequence":"additional","affiliation":[{"name":"University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Verbsky","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin Milwaukee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Spalding","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Hackensack University Medical Center Hackensack New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa F.","family":"Imundo","sequence":"additional","affiliation":[{"name":"Columbia University Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilynn G.","family":"Punaro","sequence":"additional","affiliation":[{"name":"Texas Scottish Rite Hospital Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Sherry","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey E.","family":"Tarvin","sequence":"additional","affiliation":[{"name":"Riley Hospital for Children at Indiana University Health Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence S.","family":"Zemel","sequence":"additional","affiliation":[{"name":"Connecticut Children's Medical Center Hartford"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Birmingham","sequence":"additional","affiliation":[{"name":"Michigan State University East Lansing"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth S.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Steven and Alexandra Cohen Children's Hospital New Hyde Park New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Ann and Robert H. Lurie Children's Hospital Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"O'Neil","sequence":"additional","affiliation":[{"name":"Riley Hospital for Children at Indiana University Health Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha M.","family":"Ruth","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Charleston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Seattle Children's Hospital and Research Institute Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora G.","family":"Singer","sequence":"additional","affiliation":[{"name":"Rainbow Babies and Children's Hospital and Case Medical Center Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy I.","family":"Sandborg","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(96)70140-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21774"},{"key":"e_1_2_7_4_1","first-page":"491","article-title":"Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years","volume":"27","author":"Lomater C","year":"2000","journal-title":"J Rheumatol"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0084"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200011)43:11<2402::AID-ANR5>3.0.CO;2-C"},{"key":"e_1_2_7_7_1","first-page":"2322","article-title":"Candidate early predictors for progression to joint damage in systemic juvenile idiopathic arthritis","volume":"33","author":"Sandborg C","year":"2006","journal-title":"J Rheumatol"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050473"},{"key":"e_1_2_7_9_1","first-page":"2071","article-title":"Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis","volume":"31","author":"Verbsky JW","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33342"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205099"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30128"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-008-0995-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0b013e3181a4f459"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.134254"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.076034"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm811"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38042"},{"key":"e_1_2_7_19_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_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(00)00357-7"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780371209"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400703"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1546-0096-10-31"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_7_25_1","first-page":"2290","article-title":"Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis","volume":"31","author":"Wallace CA","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2307\/2530245"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112802"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2008.24"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070070"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2011.12.008"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.68"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003163421103"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60998-8"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23437"},{"key":"e_1_2_7_35_1","first-page":"138","article-title":"Rilonacept (arcalyst), an interleukin\u20101 trap for the treatment of cryopyrin\u2010associated periodic syndromes","volume":"34","author":"Kapur S","year":"2009","journal-title":"P T"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38699","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38699","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:15:48Z","timestamp":1759954548000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.38699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,26]]},"references-count":34,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1002\/art.38699"],"URL":"https:\/\/doi.org\/10.1002\/art.38699","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,26]]}}}