Reflections on 'older' drugs: learning new lessons in rheumatology.

The management of rheumatic and musculoskeletal diseases has transformed over two decades of exciting discoveries regarding pathogenesis and innovative drug development. The introduction of sophisticated immunomodulatory therapies has given renewed hope to many patients, but notable challenges remain within the field of rheumatology. Before the advent of biologic therapies, conventional synthetic DMARDs (csDMARDs) provided effective disease control for some patients, although a comprehensive understanding of the mechanisms by which these drugs exert their effects remained elusive. Reflecting upon the efficacy and mechanisms of action of csDMARDs can provide intriguing insights. First, contemplating past approaches brings our remarkable current approaches concerning pathogenesis-driven discovery and drug development into sharper focus. Second, increased understanding of the mode of action of these older drugs might in turn provide exciting opportunities for the understanding of disease and for the development of future therapies.

JAK Inhibitors in Rheumatology: Implications for Paediatric Syndromes?

PURPOSE OF REVIEW: Given the recent increase in the profile and use of Janus kinase inhibitors (JAKinibs) in adult patients with rheumatic diseases, we aimed to review the current evidence accruing for use in paediatric rheumatology patients. RECENT FINDINGS: Significant advances have been made in the management of rheumatic diseases in the past two decades. The introduction of biologic agents in both adults and children has provided significant improvements to patient outcomes and led to better quality of life. Moreover, responses to similar agents allude to common effector pathways operating across juvenile and adult synovitis especially. However, inefficacy and intolerance of these agents leads to a subset of children with limited treatment options. Since 2012, Janus kinase (JAK) inhibitors (JAKinibs), a novel group of oral small molecule inhibitors, have demonstrated their efficacy in several forms of adult inflammatory arthritis, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). There are hopes that these successes will be transferable to the paediatric population. In the following review, we discuss the development and progress of JAKinibs in this regard.