SEARCHNARRATIVE_REVIEWpediatrics, rheumatology

narrative_review·pediatrics, rheumatology, immunology, biomedical research·PMC10571000

The clinical and experimental treatment of Juvenile Idiopathic Arthritis

Clinical and Experimental Immunology · 5 authors, 11 centres

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TL;DR

The central conclusion is a call for developing biologically stratified treatment strategies to optimize care.

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It describes JIA as the most common chronic rheumatic disease in children, detailing its clinical heterogeneity and subtypes based on joint involvement and serology. The review discusses how current therapies target the underlying inflammatory pathways for each subtype. It identifies unresolved clinical questions and future directions, advocating for the development of biologically stratified treatment strategies, optimized tapering of therapy, and less intensive maintenance treatments. The authors suggest combining therapeutic modalities early to modulate immune responses and changing the disease biology.

STUDY TYPE

narrative_review

SPECIALTY

pediatrics

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ORIGINAL PAPER

PMC10571000

The clinical and experimental treatment of Juvenile Idiopathic Arthritis

Clinical and Experimental Immunology

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ABSTRACT

Summary Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and comprises of multiple subtypes. The most relevant disease subtypes, grouped upon current insight in disease mechanisms, are nonsystemic (oligo- and polyarticular) JIA and systemic JIA (sJIA). In this review, we summarize some of the main proposed mechanisms of disease in both nonsystemic and sJIA and discuss how current therapeutic modalities target some of the pathogenic immune pathways. Chronic inflammation in nonsystemic JIA is the result of a complex interplay between effector and regulatory immune cell subsets, with adaptive immune cells, specifically T-cell subsets and antigen-presenting cells, in a central role. There is, however, also innate immune cell contribution. SJIA is nowadays recognized as an acquired chronic inflammatory disorder with striking autoinflammatory features in the first phase of the disease. Some sJIA patients develop a refractory disease course, with indications for involvement of adaptive immune pathways as well. Currently, therapeutic strategies are directed at suppressing effector mechanisms in both non-systemic and sJIA. These strategies are often not yet optimally tuned nor timed to the known active mechanisms of disease in individual patients in both non-systemic and sJIA. We discuss current treatment strategies in JIA, specifically the ‘Step-up’ and ‘Treat to Target approach’ and explore how increased insight into the biology of disease may translate into future more targeted strategies for this chronic inflammatory disease at relevant time points: preclinical disease, active disease, and clinically inactive disease. Keywords: juvenile idiopathic arthritis, translational immunology, treatment, mechanisms of disease

CITATION EXPORT

L Nijhuis, J F Swart, B J Prakken et al.. The clinical and experimental treatment of Juvenile Idiopathic Arthritis. Clinical and Experimental Immunology. (2023). https://doi.org/10.1093/cei/uxad045

AUTHORS

5 · 11 CENTRES

L Nijhuis, J F Swart, B J Prakken, J van Loosdregt, S J Vastert

1 Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
2 Department of pediatric rheumatology & immunology, University Medical Center Utrecht, Utrecht, The Netherlands
3 Department of pediatric rheumatology & immunology, University Medical Center Utrecht, Utrecht, The Netherlands
4 University of Utrecht, Utrecht, The Netherlands
5 Department of pediatric rheumatology & immunology, University Medical Center Utrecht, Utrecht, The Netherlands
6 University of Utrecht, Utrecht, The Netherlands
7 Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
8 University of Utrecht, Utrecht, The Netherlands
9 Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
10 Department of pediatric rheumatology & immunology, University Medical Center Utrecht, Utrecht, The Netherlands
11 University of Utrecht, Utrecht, The Netherlands