New Medications Are Needed for Children With Juvenile Idiopathic Arthritis

Brunner, Hermine I.; Schanberg, Laura E.; Kimura, Yukiko; Dennos, Anne; Co, Dominic O.; Colbert, Robert A.; Fuhlbrigge, Robert C.; Goldmuntz, Ellen A.; Kingsbury, Daniel J.; Patty‐Resk, Cathy; Mintz, Sandra; Onel, Karen; Rider, Lisa G.; Schneider, Rayfel; Watts, A.; Scheven, Emily von; Lovell, Daniel J.; Beukelman, Timothy

doi:10.1002/art.41390

Cited by 40 publications

(28 citation statements)

References 11 publications

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“…As an example, several biologics are approved for the indication of juvenile idiopathic arthritis (JIA). However, many children with JIA continue to have active disease despite treatment and are treated with other offlabel biologics, including anakinra, ustekinumab and golimumab (12). Infliximab and golimumab, which are not approved for JIA, are considered potential treatment options, particularly in JIA patients with rheumatoid factor positive where previous therapy was ineffective or not tolerated (13).…”

Section: Medication Uses In Recent Pediatric Clinical Practicementioning

confidence: 99%

Off-label medication use in rare pediatric diseases in the United States

Fung

Yue

Wigle

et al. 2021

IRDR

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rare diseases, off-label drug use, pediatrics, infants, children.Many pediatric patients with rare diseases use drugs off-label due to limited data in pediatric patients. Off-label treatment remains an important public health issue for neonates, infants, children, and adolescents, especially for pediatric patients with rare diseases. For patients with rare diseases, the majority of medications have no or limited information in labelling for pediatric use. Children present unique considerations in clinical trials due to ethical and clinical concerns, which have limited and even discouraged testing of drugs in the pediatric population. Numerous legislative measures have been enacted to address barriers in pediatric drug testing. This research reviewed off-label medication use in rare pediatric diseases, evaluated recent medication uses in pediatric clinical practice, discussed key regulations for rare pediatric diseases, and summarized recent drug approvals for rare pediatric diseases. This study demonstrates the ongoing medical need for newly approved medications to treat pediatric rare diseases and revealed the positive impact of regulations from the Orphan Drug Act of 1983 to the Research to Accelerate Cures and Equity (RACE) for Children Act on drug development and off-label medication practice in rare pediatric disease management. This article provides informative historical background and current considerations of off-label use of medications in neonates, infants, children, and adolescents with rare diseases.

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Section: Medication Uses In Recent Pediatric Clinical Practicementioning

confidence: 99%

Off-label medication use in rare pediatric diseases in the United States

Fung

Yue

Wigle

et al. 2021

IRDR

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“…Comparable outcomes were reported in a 2020 comprehensive study on unmet needs in JIA. Brunner et al described 2 large cohorts, one from Cincinnati Children's (CHMC) and another from the multi-site Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, including 279/1351 with ERA/PsA and 50/164 with undifferentiated arthritis (82). In the two cohorts, 79 and 72% of children with ERA/PsA were treated with biologics.…”

Section: Remission Rates and Biologic Dmardsmentioning

confidence: 99%

Outcomes in Juvenile-Onset Spondyloarthritis

Smith

Burgos‐Vargas

2021

Front. Med.

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Some studies have suggested children with juvenile onset spondyloarthritis (JoSpA) have a relatively poor outcome compared to other juvenile idiopathic arthritis (JIA) categories, in regards to functional status and failure to attain remission. Thus, in the interest of earlier recognition and risk stratification, awareness of the unique characteristics of this group is critical. Herein, we review the clinical burden of disease, prognostic indicators and outcomes in JoSpA. Of note, although children exhibit less axial disease at onset compared to adults with spondyloarthritis (SpA), 34–62% have magnetic resonance imaging (MRI) evidence for active inflammation in the absence of reported back pain. Furthermore, some studies have reported that more than half of children with “enthesitis related arthritis” (ERA) develop axial disease within 5 years of diagnosis. Axial disease, and more specifically sacroiliitis, portends continued active disease. The advent of TNF inhibitors has promised to be a “game changer,” given their relatively high efficacy for enthesitis and axial disease. However, the real world experience in various cohorts since the introduction of more widespread TNF inhibitor usage, in which greater than a third still have persistently active disease, suggests there is still work to be done in developing new therapies and improving the outlook for JoSpA.

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“…Most JIA patients attain inactive disease with therapies; however, the likelihood of disease flare is over 50% in the first 2 years after attaining inactive disease (3, 4). Moreover, chronically uncontrolled JIA occurs in half of patients that require multiple DMARDs during treatment (5). Critical needs exist for a personalized approach to current therapies and development of new therapies.…”

Section: Introductionmentioning

confidence: 99%

JIA patient T cells differentiate into Th1, Th17 and Th1.17 effector cells under Th1 polarizing conditions

Esmond

Shoaff

et al. 2021

Preprint

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Objective. T helper cells develop into discrete Th1, Th2 or Th17 lineages that selectively express IFN-gamma, IL-4/IL-5/IL-13, or IL-17, respectively and actively silence signature cytokines expressed by opposing lineages. Our objective was to compare Th1, Th2 and Th17 polarization in cell culture models using JIA patient samples. Methods. Peripheral blood mononuclear cells were isolated from JIA or healthy prepubescent children. T cell naive and memory phenotypes were assessed by flow cytometry. T cell proliferation was measured using a fluorescence-based assay. Th cell cultures were generated in vitro and IFN-gamma, IL-17, and TNF-alpha measured by ELISA and flow cytometry. Results. JIA Th1 cells produced increased IFN-gamma and inappropriately produced IL-17. JIA Th17 cells produced increased IL-17. JIA Th1 cell cultures develop dual producers of IFN-gamma and IL-17, which are Th1.17 cells. JIA Th1 cultures expressed elevated levels of both T-bet and ROR-gamma-T. RNA sequencing confirmed activation of immune responses and inappropriate activation of IL-17 signaling pathways in Th1 cultures. A subset of JIA patient samples was disproportionally responsible for the enhanced IFN-gamma and IL-17 phenotype and Th1.17 phenotype. Conclusions. This study reveals that JIA patient uncommitted T cell precursors, but not healthy children, inappropriately develop into inflammatory effector Th1.17 and Th17 cells under Th1 polarizing conditions.

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New Medications Are Needed for Children With Juvenile Idiopathic Arthritis

Cited by 40 publications

References 11 publications

Off-label medication use in rare pediatric diseases in the United States

Off-label medication use in rare pediatric diseases in the United States

Outcomes in Juvenile-Onset Spondyloarthritis

JIA patient T cells differentiate into Th1, Th17 and Th1.17 effector cells under Th1 polarizing conditions

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