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Effective and safe medications are essential because there are generally no cures for these conditions. Etanercept was the first biologic therapy for the treatment of JIA, approved in 1999. Since then, other biologic disease\u2010modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease\u2010modifying antirheumatic drugs (tsDMARDs) blocking relevant immunologic pathways have been approved for the treatment of JIA, resulting in a marked improvement of disease prognosis. Conversely, there is only one bDMARD that has been approved for cSLE, but none are approved for the treatment of JDM. Lack of approved therapeutic options, with established dosing regimens and known efficacy and safety, remains a central challenge in the treatment of all PRDs, including autoinflammatory diseases, and for complications of PRDs. This review provides an overview of bDMARD and tsDMARD treatments studied for the treatment of various subtypes of JIA, summarizes information from bDMARD studies in other PRDs, with a focus on pivotal trials that led to regulatory approvals, and highlights improved outcomes in patients with JIA with the reception of these newer medications. Further, we outline barriers and challenges in the treatment of other PRDs. Last, we summarize the current regulatory landscape for bDMARD studies and medication approvals for patients with PRDs.<\/jats:p>","DOI":"10.1002\/acr.25482","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T06:10:02Z","timestamp":1733724602000},"page":"573-583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["25 Years of Biologics for the Treatment of Pediatric Rheumatic Disease: Advances in Prognosis and Ongoing Challenges"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-315X","authenticated-orcid":false,"given":"Michael","family":"Shishov","sequence":"first","affiliation":[{"name":"Phoenix Children's Hospital  Phoenix Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9724-0443","authenticated-orcid":false,"given":"Pamela 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