{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:53:47Z","timestamp":1784202827776,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,24]],"date-time":"2019-11-24T00:00:00Z","timestamp":1574553600000},"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":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"\n Objective<\/jats:title>\n \n Biologics have an important role in the treatment of juvenile idiopathic arthritis (\n JIA<\/jats:styled-content>\n ). Long\u2010term safety data are limited. Direct comparison of different agents regarding occurrence of adverse events (\n AE<\/jats:styled-content>\n s), especially of rare events, requires large quantities of patient years. In this analysis, long\u2010term safety with regard to\n AE<\/jats:styled-content>\n of special interest (\n AESI<\/jats:styled-content>\n ) was compared between different biologics.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Patients with nonsystemic\n JIA<\/jats:styled-content>\n were selected from the German\n BIKER<\/jats:styled-content>\n registry. Safety assessments were based on\n AE<\/jats:styled-content>\n reports. Number of\n AE<\/jats:styled-content>\n s, serious\n AE<\/jats:styled-content>\n s, and 25 predefined\n AESI<\/jats:styled-content>\n s, including medically important infection, uveitis, inflammatory bowel disease, cytopenia, hepatic events, anaphylaxis, depression, pregnancy, malignancy, and death, were analyzed. Event rates and relative risks were calculated using\n AE<\/jats:styled-content>\n s reported after first dose through 70 days after last dose.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 3873 patients entered the analysis with 7467 years of exposure to biologics. The most common\n AESI<\/jats:styled-content>\n s were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequent with tocilizumab (risk ratio [\n RR<\/jats:styled-content>\n ] 8.0, 95% confidence interval [\n CI<\/jats:styled-content>\n ] 4.2\u201015, and\n RR<\/jats:styled-content>\n 4.7, 95%\n CI<\/jats:styled-content>\n 1.8\u201012.2, respectively). Anaphylactic events were associated with intravenous route of administration. In patients ever exposed to biologics, eight malignancies were reported. Six pregnancies have been documented in patients with tumor necrosis factor inhibitors. No death occurred in this patient cohort during observation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Surveillance of pharmacotherapy as provided by the\n BIKER<\/jats:styled-content>\n registry is an import approach, especially for long\u2010term treatment of children. Overall, tolerance was acceptable. Differences between biologics were noted and should be considered in daily patient care.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/acr2.11091","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T01:10:20Z","timestamp":1574644220000},"page":"37-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Biologic Therapies in Polyarticular Juvenile Idiopathic Arthritis. Comparison of Long\u2010Term Safety Data from the German\n BIKER<\/scp>\n Registry"],"prefix":"10.1002","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9771-8710","authenticated-orcid":false,"given":"Ariane","family":"Klein","sequence":"first","affiliation":[{"name":"Asklepios Klinik Sankt Augustin, Sankt Augustin, Germany, and University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Becker","sequence":"additional","affiliation":[{"name":"University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Minden","sequence":"additional","affiliation":[{"name":"German Rheumatism Research Centre Berlin, Berlin and Charit\u00e9 University Medicine Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Hospach","sequence":"additional","affiliation":[{"name":"Olga Hospital Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Schwarz","sequence":"additional","affiliation":[{"name":"St. Josef\u2010Stift Sendenhorst Sendenhorst Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Foeldvari","sequence":"additional","affiliation":[{"name":"Hamburg Centre for Pediatric and Adolescent Rheumatology Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1145-6719","authenticated-orcid":false,"given":"Boris","family":"Huegle","sequence":"additional","affiliation":[{"name":"German Centre for Pediatric and Adolescent Rheumatology Garmisch\u2010Partenkirchen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Borte","sequence":"additional","affiliation":[{"name":"Children's Hospital Sankt Georg Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Weller\u2010Heinemann","sequence":"additional","affiliation":[{"name":"Prof. Hess Children's Hospital Bremen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Dressler","sequence":"additional","affiliation":[{"name":"Hanover Medical School Hanover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Kuemmerle\u2010Deschner","sequence":"additional","affiliation":[{"name":"University Hospital Tuebingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasad Thomas","family":"Oommen","sequence":"additional","affiliation":[{"name":"University Hospital D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1946-3916","authenticated-orcid":false,"given":"Dirk","family":"Foell","sequence":"additional","affiliation":[{"name":"University Children's Hospital M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Trauzeddel","sequence":"additional","affiliation":[{"name":"Helios Klinik Berlin\u2010Buch Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Rietschel","sequence":"additional","affiliation":[{"name":"Clementine Children's Hospital Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Horneff","sequence":"additional","affiliation":[{"name":"Asklepios Klinik Sankt Augustin, Sankt Augustin, Germany, and University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,24]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1377","article-title":"Epidemiology of juvenile idiopathic arthritis in Alsace, France","volume":"33","author":"Danner S","year":"2006","journal-title":"J Rheumatol"},{"key":"e_1_2_9_3_1","first-page":"622","article-title":"Health care provision in pediatric rheumatology in Germany\u2013national rheumatologic database","volume":"29","author":"Minden K","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1287837"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20460"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.014886"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.087593"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes019"},{"key":"e_1_2_9_9_1","unstructured":"ICH Harmonised Guideline.Integrated addendum to ICH E6(R1): guideline for good clinical practice E6(R2).2016. 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