Investigational drugs for treatment of juvenile idiopathic arthritis

ABSTRACT

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The improvement of knowledge about the pathogenetic mechanisms of JIA and advances in the understanding of pathways linking inflammation and autoimmunity and functions of multiple transcription factors have translated into new drug development for a tailored treatment directed to specific subpopulations of JIA patients.

Areas covered: This review provides a digest of new investigational drugs which are currently or have been recently tested for treatment of JIA, and highlights some early phase clinical trials on rilonacept, givinostat, daclizumab, tofacitinib, and sarilumab.

Expert opinion: Several studies have been focused on multiple complementary pathways driving synovial inflammation in JIA or molecules implicated in the inflammatory signature of JIA to deliver durable effects and prevent long-term complications. Since JIA is a complex disorder with multiple faces, identifying new treatment options for patients nonresponsive to the current drug armamentarium is of great relevance. A number of agents have been developed in the very last years, such as givinostat and tofacitinib, showing promising results in some cases, but trials remain in an early phase and few agents are currently under evaluation in a further phase setting. Longer-term use in possibly high numbers of patients and adequate data collection using large-scale registries are necessary to confirm clinical efficacy and provide a well-balanced overview of safety issues related to the drugs presented in this review.

KEYWORDS:

• Investigational drugs
• juvenile idiophatic arthritis
• phase 1 studies
• phase 2 studies

Article highlights

• New treatments have been evaluated for a more personalized treatment of juvenile idiopathic arthritis (JIA) and to improve long-term outcome of each JIA category.

• Rilonacept has shown a good efficacy in active systemic JIA, though inferior to other interleukin-1 antagonists and even interleukin-6 antagonists, and an acceptable safety profile.

• Evidences have shown both efficacy and safety of high dose givinostat in patients with systemic JIA, but its therapeutic role in the management of polyarthritis still requires further investigation.

• Few data are available for attributing high efficacy to daclizumab in the treatment of refractory JIA-related uveitis.

• An open-label non-randomized multiple dose phase 1 study with tofacitinib has evaluated both its pharmacokinetics and safety in pediatric patients with active polyarthritis.

• A study is underway to evaluate the best dosing regimen of subcutaneously injected sarilumab in children with polyarthritis.

• Treating refractory patients with JIA remains a challenging goal, and trials in progress will hopefully find new therapeutic tools to ameliorate the overall prognosis of this disorder.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.