{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:02:04Z","timestamp":1790179324205,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study was designed as a 2\u2010part phase IIIb\/IV open\u2010label, randomized trial. In the first part, patients received 4 mg\/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and\/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg\/kg to 2 mg\/kg and then to 1 mg\/kg, followed by discontinuation. In arm 2, the 4 mg\/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether &gt;40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg\/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg\/kg every 8 weeks) (<jats:italic>P<\/jats:italic> \u2264 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consistent interleukin\u20101 inhibition appears necessary to maintain this response.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41488","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T02:43:24Z","timestamp":1597200204000},"page":"336-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Tapering Canakinumab Monotherapy in Patients With Systemic Juvenile Idiopathic Arthritis in Clinical Remission: Results From a Phase IIIb\/IV Open\u2010Label, Randomized Study"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1769-549X","authenticated-orcid":false,"given":"Pierre","family":"Quartier","sequence":"first","affiliation":[{"name":"RAISE Reference Centre for Rare Diseases, Necker\u2013Enfants Malades, AP\u2010HP, Imagine Institute Paris University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Alexeeva","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Children\u2019s Health of the Ministry of Health of the Russian Federation Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e0s","family":"Constantin","sequence":"additional","affiliation":[{"name":"Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyacheslav","family":"Chasnyk","sequence":"additional","affiliation":[{"name":"Saint\u2010Petersburg State Pediatric Medical University  Saint\u2010Petersburg Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Wulffraat","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Palmblad","sequence":"additional","affiliation":[{"name":"Karolinska Institutet Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Wouters","sequence":"additional","affiliation":[{"name":"University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9478-2987","authenticated-orcid":false,"given":"Hermine","family":"I. Brunner","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Marzan","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles  Los Angeles California United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayfel","family":"Schneider","sequence":"additional","affiliation":[{"name":"University of Toronto and Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Horneff","sequence":"additional","affiliation":[{"name":"Asklepios Klinik Sankt Augustin and University Hospital Cologne  Sankt Augustin Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Martini","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini IRCCS  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8792-4219","authenticated-orcid":false,"given":"Jordi","family":"Anton","sequence":"additional","affiliation":[{"name":"Hospital Sant Joan de D\u00e9u Esplugues de Llobregat, Spain, and Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Wei","sequence":"additional","affiliation":[{"name":"China Novartis Institutes for Biomedical Research, Ltd  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Slade","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8407-7782","authenticated-orcid":false,"given":"Nicolino","family":"Ruperto","sequence":"additional","affiliation":[{"name":"Clinica Pediatrica e 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