Scope of JAK Inhibitors in Children: Recent Evidence and Way Forward.

Abstract

Over the last decade, there has been an increase in the use of targeted therapy using small molecules such as Janus kinase (JAK) inhibitors. Since the introduction of ruxolitinib, the first non-selective JAK inhibitor approved for use in myelofibrosis, many other JAK inhibitors have been tried in a wide spectrum of immune-mediated disorders. Although various trials have shown the promising efficacy of JAK inhibitors in immune-mediated inflammatory disorders (IMIDs), there is a growing concern over the major cardiovascular events and malignancies associated with the use of these molecules in older adults, particularly those over 65 years of age. In this review, we aim to discuss the immunology of the JAK-STAT pathway, the scope of use of JAK inhibitors, and their safety in paediatric practice. Here, we discuss high-quality evidence favouring the use of JAK inhibitors in children with juvenile idiopathic arthritis (JIA) who are refractory to one or more conventional/biological disease-modifying drugs, demonstrated in two randomised controlled trials (RCTs). In addition to JIA, there are reports favouring the role of JAK inhibitors in other IMIDs such as systemic-onset JIA and interferonopathies. Thus far, the existing literature suggests an acceptable safety profile for JAK inhibitors in children. With the expanding scope of JAK inhibitors in a wide range of IMIDs in children, there is a significant need for long-term close vigilance for any potential harm.