Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis

Abstract

In childhood arthritis, collectively known as Juvenile idiopathic arthritis (JIA), the rapid rise of available licensed biological and targeted small molecule treatments in recent years has led to improved outcomes. However, real-world data from multiple countries and registries show that despite a large number of available drugs, many children and young people continue to suffer flares and experience significant periods of time with active disease for many years. More than 50% of young people with JIA require ongoing immune suppression well into adult life, and they may have to try multiple different treatments in that time. There are currently no validated tools with which to select specific treatments, nor biomarkers of response to assist in such choices, therefore, current management uses essentially a trial-and-error approach. A further consequence of recent progress is a reducing pool of available children or young people who are eligible for new trials. In this review we consider how progress towards a molecular based approach to defining treatment targets and informing trial design in JIA, combined with novel approaches to clinical trials, could provide strategies to maximise discovery and progress, in order to move towards precision medicine for children with arthritis.

Novel therapies in juvenile idiopathic arthritis

“…There is a drive for precision patient-specific medicine, with focus on determination of biomarkers associated with response to treatment. This requires international collaboration, review of study design to optimize patient recruitment, industry support and significant patient and family involvement [47 ▪ ].…”

Relapses of juvenile idiopathic arthritis in adulthood: A monocentric experience

“…ANA carriers with oligoarticular involvement are at higher risk of developing chronic anterior uveitis (CUA), an asymptomatic iridocyclitis that can cause serious visual impairment and ocular complications [ 4 ]. The current ILAR classification criteria appear to be inadequate to implement JIA treatment and predict outcome [ 5 , 6 ], in light of recent evidence on JIA pathogenesis. The classification and outcomes of disease phenotypes are still ill-defined in the paediatric age, and is the case in adulthood for outcomes and predictors [ 7 , 8 ].…”

T lymphocytes-related cell network in the pathogenesis of juvenile idiopathic arthritis: a key point for personalized treatment

“…First line therapies are nonsteroidal anti-inflammatory drugs (NSAIDs), however in case of reduced symptoms control an immunosuppressive therapy with disease modifying antirheumatic drugs (DMARDs) can be initiated. Novel biological drugs selectively targeting cytokines [interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-a], B cells (CD20) or T cell costimulation (CTLA-4) have also proven efficacy in patients with limited response to first line therapy [5][6][7]. The finding that different patients display different responses to biological drugs further supports the heterogeneity of pathogenic mechanisms in JIA, with specific cellular and molecular mechanisms driving inflammation in each patient.…”