Update on Biologic Therapy in Juvenile Idiopathic Arthritis: A Five-year Narrative Review.

The "biologic era" in the management of juvenile idiopathic arthritis (JIA) has begun in the year 2000, with the publication of the randomized controlled trial on etanercept. In the subsequent years, there has been continued progress, marked by the availability of new therapeutic agents and the shift towards early aggressive interventions. In addition, a more rational therapeutic approach has been fostered by the promulgation of therapeutic recommendations and guidelines. In parallel with the growing use of the novel biologic disease-modifying antirheumatic drugs (bDMARDs) in the real world of clinical practice, additional information has been gained about their effectiveness and safety. Furthermore, the role of the various bDMARDs in the management of the different JIA categories and of the main disease complications and comorbidities has been scrutinized. Innovative management strategies, such as the step-down and the treat-to-target, have been proposed to maximize the therapeutic benefits through the optimal combination of the newer and conventional medications. However, despite this progress several unmet needs remain, including the lack of well-established criteria for medication discontinuation after the attainment of sustained disease remission and of effective alternatives for patients who respond inadequately to the contemporary therapeutic modalities. The research agenda also calls for the search for reliable early predictors of therapeutic response that foster personalization of treatment and increase its precision. The aim of this Review is to summarize the evidence obtained in the past 5 years in the field of biologic therapy for JIA and to discuss the remaining gaps and the future perspectives of the use of these medications.