{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:15:53Z","timestamp":1784286953753,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We evaluate tofacitinib efficacy and safety in patients with juvenile idiopathic arthritis (JIA) stratified by concomitant methotrexate and prior biologic disease\u2010modifying antirheumatic drug (bDMARD) treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this two part, double\u2010blind, randomized withdrawal Phase 3 trial (NCT02592434), patients (2\u2013&lt;18 years) with JIA received open\u2010label tofacitinib (5 mg twice daily\/weight\u2010based equivalent) in Part 1 (Day 1\u2013Week 18). Those eligible were randomized to continue tofacitinib or switch to placebo in Part 2 (Weeks 18\u201344). In this post hoc analysis, patients were stratified by concomitant methotrexate (MTX+\/\u2212) and prior bDMARD treatment (bDMARD+\/\u2212). Efficacy outcomes included JIA disease flare, JIA\/American College of Rheumatology (ACR) 50\/70 response rates, and JIA\/ACR clinical inactive disease (CID). Safety was assessed throughout the trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 225 patients in Part 1, 147 (65.3%) were MTX+; 85 (37.8%) were bDMARD+. Across subgroups, JIA flare rate at Week 44 was lower with tofacitinib than placebo: patients who were MTX+ (29.8% vs 47.5%), patients who were MTX\u2212 (32.3% vs 73.1%), patients who were bDMARD+ (29.0% vs 70.4%), patients who were bDMARD\u2212 (31.6% vs 48.3%). Greater JIA\/ACR50\/70 and JIA\/ACR\u2010CID responses with tofacitinib than with placebo were observed across subgroups. In tofacitinib\u2010treated patients, adverse events (AEs) were more common in the subgroups of patients who were MTX\u2212 (85.9%) and patients who were bDMARD+ (81.2%) than the subgroups of patients who were MTX+ (74.1%) and patients who were bDMARD\u2212 (76.4%). Similar findings were observed with serious AEs\/discontinuations due to AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tofacitinib was efficacious for patients regardless of baseline concomitant MTX treatment or prior bDMARD exposure; MTX may have a protective effect for flare upon tofacitinib withdrawal. Safety was consistent with the known tofacitinib profile, and no new risks were identified in these subgroups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acr2.70097","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T06:52:39Z","timestamp":1759906359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Concomitant Methotrexate Use and Prior Biologic Disease\u2010Modifying Antirheumatic Drug Exposure on Tofacitinib Efficacy and Safety in Patients with Polyarticular Course Juvenile Idiopathic Arthritis: Post Hoc Analysis of a Phase 3 Randomized Withdrawal Trial"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8407-7782","authenticated-orcid":false,"given":"Nicolino","family":"Ruperto","sequence":"first","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano\u2010Bicocca, Milan, and Fondazione IRCCS San Gerardo dei Tintori\/Paediatric Rheumatology International Trials Organisation (PRINTO)  Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1604-0130","authenticated-orcid":false,"given":"Daniel J.","family":"Lovell","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center and University of Cincinnati  Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Synoverska","sequence":"additional","affiliation":[{"name":"Regional Children's Hospital  Ivano\u2010Frankivsk Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3749-5831","authenticated-orcid":false,"given":"Carlos","family":"Abud\u2010Mendoza","sequence":"additional","affiliation":[{"name":"Regional Unit of Rheumatology and Osteoporosis at Central Hospital, Faculty of Medicine  San Luis Potos\u00ed Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Spindler","sequence":"additional","affiliation":[{"name":"Centro M\u00e9dico Privado de Reumatologia  Tucum\u00e1n Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3237-9962","authenticated-orcid":false,"given":"Yulia","family":"Vyzhga","sequence":"additional","affiliation":[{"name":"Vinnytsya National Medical University N Pirogov  Vinnytsya Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Reyhan","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyudmila","family":"Grebenkina","sequence":"additional","affiliation":[{"name":"Togliatti City Clinical Hospital Number 5  Togliatti 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Children's Hospital at Legacy Emanuel  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Sozeri","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, \u00dcmraniye Training and Research Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2036-8622","authenticated-orcid":false,"given":"Sheetal S.","family":"Vora","sequence":"additional","affiliation":[{"name":"Pediatric Rheumatology Atrium Health Levine Children's Hospital and Wake Forest University School of Medicine  Charlotte North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3489-1756","authenticated-orcid":false,"given":"Sampath","family":"Prahalad","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Human Genetics Emory University School of Medicine and Children's Healthcare of Atlanta  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Zholobova","sequence":"additional","affiliation":[{"name":"Institute of Children's Health, University Children's Clinical Hospital, Sechenov University  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gosford","family":"Sawyerr","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Blum","sequence":"additional","affiliation":[{"name":"Pfizer Pharma GmbH  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Pearl River New 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I.","family":"Brunner","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center and University of Cincinnati  Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"issue":"2","key":"e_1_2_8_2_1","first-page":"390","article-title":"et al; International League of Associations for Rheumatology. 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Review of the general methodology","volume":"19","author":"Ruperto N","year":"2001","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200108)44:8<1768::AID-ART312>3.0.CO;2-Q"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210456"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41528"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706290"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27670"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-207178"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-219601"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31618-5"}],"container-title":["ACR Open Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr2.70097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T14:18:12Z","timestamp":1761747492000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/acr2.70097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/acr2.70097"],"URL":"https:\/\/doi.org\/10.1002\/acr2.70097","archive":["Portico"],"relation":{},"ISSN":["2578-5745","2578-5745"],"issn-type":[{"value":"2578-5745","type":"print"},{"value":"2578-5745","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70097"}}