Patterns and determinants of response to novel therapies in juvenile and adult-onset polyarthritis

Abstract

Biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Amongst these, polyarticular juvenile idiopathic arthritis (pJIA) and rheumatoid arthritis (RA) display similarities in terms of disease pathophysiology and response pattern to b/tsDMARDs. Indeed, therapeutic efficacy of novel targeted drugs is variable among individual patients, in both RA and pJIA. Mechanisms and determinants of this heterogeneous response are diverse and complex, such that development of true “precision”-medicine strategies has proven highly challenging. In this review, we will discuss pathophysiological, patient-specific, drug-specific and environmental factors contributing to individual therapeutic response in polyarticular JIA in comparison to what is known in RA. Although some biomarkers have been identified that stratify for the likelihood of either therapeutic response or non-response, few have proved useful in clinical practice so far, likely due to the complexity of treatment-response mechanisms. Consequently, we propose a pragmatic, patient-centered and clinically-based approach, i.e. personalized instead of biomarker-based precision medicine in JIA.