Role of methotrexate in juvenile idiopathic arthritis: where we have been and where we are going

Methotrexate is a cornerstone of therapy worldwide for juvenile idiopathic arthritis, yet there remains vast variability in drug dosing and administration, as well as unpredictable outcomes on the drug. Recent efforts through worldwide organization and collaboration have resulted in large registries from which we can now collect clinical data, attempts to standardize therapeutic management with methotrexate and ongoing goals to further individualize drug therapy. Recent studies in juvenile idiopathic arthritis have begun to predict outcomes on the drug by investigating clinical, genetic and cellular biomarkers in children. Pediatric rheumatology as a field has grown from extrapolating data from adult studies to overcoming the barriers to conduct needed investigations in children; however, there remains much to learn and discover about this commonly used drug in juvenile idiopathic arthritis. This nonsystematic review will briefly discuss the history of methotrexate use in juvenile arthritis, the current clinical challenges practitioners face in the variability of drug utilization and drug outcomes, and highlight recent research that has focused on investigating factors that contribute to this variability.