Updates on efficacy and safety janus kinase inhibitors in juvenile dermatomyositis

ABSTRACT

Introduction

Juvenile dermatomyositis (JDM) is a rare autoimmune disease most commonly with proximal weakness due to inflammation and characteristic skin rashes. Most patients have a chronic or polycyclic disease course on standard therapy so better treatments are needed. An interferon signature is well-established in key tissues of JDM. Janus kinase inhibitors (jakinibs), which can decrease IFN signaling, are therefore appealing as a targeted therapy.

Areas covered

Herein is a review of the growing literature on JDM patients in jakinibs, including specifics of their jakinib exposure, summary of efficacy, disease features, and characteristics of patients treated, and safety parameters.

Expert opinion

The vast majority of refractory JDM patients respond to jakinib therapy, though they have varied features, doses, and previous/concurrent medications, and data is largely retrospective. Jakinibs are an exciting and promising treatment in JDM. Evaluation with larger prospective controlled studies is needed to answer remaining questions about jakinibs in JDM regarding dosing, which JDM patients to treat with jakinibs, potential biomarkers to use, and how best to monitor safety risks in JDM.

KEYWORDS:

• Baricitinib
• efficacy
• interferon
• janus kinase inhibitor
• juvenile dermatomyositis
• ruxolitinib
• safety
• tofacitinib

Article highlights

• There are more than 150 largely retrospective and mostly refractory JDM patients on jakinibs reported in literature generally with clinical improvement, allowing for weaning of steroids in most and weaning of other immunosuppressants in some.

• The vast majority of JDM patients on jakinibs had skin disease activity that generally improved and about one-third had muscle disease activity that generally improved.

• For some JDM patients, there was notable improvement or stabilization of calcinosis, which is difficult to manage, and ILD, which has significant morbidity and rare mortality.

• Given the increased IFN signature noted in JDM, jakinib targeting of IFN signaling has been assessed by different markers and generally found to decrease with jakinib treatment.

• Safety assessment of jakinibs in JDM has been limited, but has noted infections including herpes simplex and herpes zoster and changes in cell counts as in other pediatric conditions. Notable for JDM, variable elevation of muscle enzymes have been noted, not associated with increased muscle inflammation or muscle weakness.

• Future larger randomized controlled trials are needed to better assess efficacy, dosing, predictors of response, and safety of jakinibs in JDM.

Declaration of interest

The author had a Cooperative Agreement with for a study of baricitinib in juvenile dermatomyositis. Otherwise, the author has 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.

Acknowledgments

This work was supported by the US NIH Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases. Owing to how fast this field is moving, the author apologize for any studies, or approvals that may have been missed.

Reviewer disclosures

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

Additional information

Funding

This paper was funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.