Therapeutic Potential of Janus Kinase Inhibitors in Juvenile Idiopathic Arthritis

Abstract

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of rheumatic diseases characterized by chronic joint inflammation that begins before the age of 16 [1]. The term “JIA” encompasses seven distinct subtypes, each with unique clinical features, treatment approaches, and prognoses [2]. Current guidelines for managing JIA include a stepwise approach involving nonsteroidal anti-inflammatory drugs (NSAIDs), non-biologic disease-modifying antirheumatic drugs (DMARDs), and biologic DMARDs (bDMARDs). Biologic treatments include interleukin-1 (IL-1) inhibitors, interleukin-6 (IL-6) inhibitors, tumor necrosis factor (TNF) inhibitors, T-cell inhibitors, and anti-B cell therapies. Glucocorticoids (GCs) are often used as adjunctive therapy.

Despite significant advances in treating JIA over the past two decades, several challenges remain. Long-term use of corticosteroids and NSAIDs can lead to hepatic and renal toxicity, and IL-1 inhibitors may be associated with inflammatory liver infiltrates, particularly in systemic JIA (sJIA) patients [3-5]. Complications such as uveitis and macrophage activation syndrome (MAS) further complicate treatment, increasing the complexity of disease management [6, 7]. These challenges highlight the need for new therapeutic options, including Janus kinase (JAK) inhibitors, to improve outcomes for patients with JIA. Recent advances have introduced JAK inhibitors as a promising therapeutic option [8], particularly for patients with refractory JIA who do not respond to bDMARDs [9]. JAK inhibitors act by targeting the JAK–STAT signaling pathway, which is crucial in the pathogenesis of autoimmune diseases. This editorial explores the current evidence regarding using JAK inhibitors in JIA, emphasizing their efficacy and safety profiles.

JAK inhibitors are a promising therapeutic option for children with refractory JIA, particularly those with complications like MAS and uveitis. Early clinical trials and observational studies indicate they reduce disease activity, improve outcomes, and act as corticosteroid-sparing agents. However, the long-term safety and optimal dosing strategies require further investigation. As ongoing trials provide more data, JAK inhibitors could become a cornerstone for treating difficult-to-treat JIA.

Y.X.L., C.D., and B.S.C. write the draft paper. Y.X.L., C.D., and B.S.C. collect the references. Y.X.L., A.P.H., conceived this article. A.P.H. corrected and finalized the draft paper to the final version.

The authors declare no conflicts of interest.