25 Years of Biologics For The Treatment of Pediatric Rheumatic Diseases - Advances in Prognosis and Ongoing Challenges.

Abstract

There are over 100 rheumatic diseases and approximately 300,000 children with a pediatric rheumatic disease (PRD) in the United States (U.S.). The most common PRDs are juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), and juvenile dermatomyositis (JDM). 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 modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARD (tsDMARDs) blocking relevant immunological 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 pediatric rheumatic diseases, with a focus on pivotal trials that led to regulatory approvals and highlights improved outcomes in JIA with the use of these newer medications. Further, we outline barriers and challenges in the treatment of other PRDs. Lastly, we summarize the current regulatory landscape for bDMARD studies and medication approvals in PRDs.