Evaluating the use of JAK inhibitors in inflammatory connective tissue diseases in pediatric patients: an update

ABSTRACT

Introduction

Connective tissue diseases (CTDs) are a category of conditions that affect tissues that support and provide structure to the body. These diseases include rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, and sclerosing diseases. CTDs can be caused by dysregulation of inflammatory pathways, specifically an upregulation of interferons and JAK/STAT pathway activation.

Areas covered

While CTDs have historically been treated with broadly immunosuppressant medications such as corticosteroids and disease-modifying antirheumatic drugs (DMARDS), newer and more targeted immunomodulating medications called Janus kinase inhibitors (JAKi) have emerged as potential treatments.

Expert opinion

While most studies regarding JAKi for CTDs have focused on adult populations, pediatric patients with CTDs may also benefit from JAKi therapy. Moreover, the JAK/STAT inhibitor tofacitinib has been approved by the FDA for the treatment of active polyarticular course juvenile idiopathic arthritis. In this review, we have summarized what has been published on the use of JAKi for various pediatric CTDs.

KEYWORDS:

• Children
• connective tissue disease
• janus-kinase inhibitor
• pediatric

Acknowledgments

We would like to acknowledge Tess Grynoch, a research librarian at the University of Massachusetts Chan Medical School, who assisted with the literature search parameters for this review article. Ms Grynoch is aware and consented to be named in the manuscript.

Article highlights

• JAKi are potential treatments for CTD management given that they block a complicated myriad of cytokines rather than a single cytokine, yet they are more targeted than conventional immunosuppressive treatments, including systemic corticosteroids or rituximab.

• JAKi are increasingly being used for adults with CTDs and may also be beneficial for pediatric CTDs.

• Limited anecdotal reports suggest that JAKi may provide significant clinical improvement in pediatric CTD cases that are refractory to standard treatments. These include patients with juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, type 1 interferonopathies, and sclerosing diseases.

• Oral tofacitinib was recently approved by the FDA for the treatment of active polyarticular course juvenile idiopathic arthritis in patients over the age of 2.

• Although JAKi appear to be well tolerated and could be used in combination with other medications, future randomized-controlled trials are necessary to fully assess their safety and efficacy.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.