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Are we closer to personalized therapy in juvenile idiopathic arthritis?

Elżbieta Smolewska

Data publikacji online: 2016/10/05
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Juvenile idiopathic arthritis (JIA) is the most common rheumatic disorder in children. However, actually this term encompasses a heterogeneous group of disorders. Their classification is based on clinical and laboratory features occurring in the 6 months after the disease onset. Most importantly, different subtypes of JIA can still be associated with permanent disability and significant morbidity.
Over the last decades a dramatic improvement in treatment of JIA has been noted. Introduction of methotrexate (MTX) in the late 1980s was the first milestone, described as the first revolution in this disease [1]. This caused transformation of JIA from an untreatable disease into a manageable condition. Unfortunately, although the therapeutic benefits of MTX in JIA are well established, only 30–50% of children have an adequately effective response to this treatment, and several adverse effects are noted in many patients. In 2011 Hinks et al. [2] reported a study in JIA patients which demonstrated that tagging single nucleotide polymorphisms (SNPs) across genes involved in the MTX metabolic pathway could reveal MTX efficacy. Three years later, the first large genome-wide pharmacogenetic study in JIA patients (N = 759) treated with MTX reported novel pathways in the MTX-induced response and identified three genes of particular interest (CFTR, TGIF1 and ZMIZ1) [3].
Ten years after MTX implementation, the introduction of biologically targeted agents led to a second leap forward in the treatment of JIA. It is one of the few real successes of translational medicine in the past decades. Although further experiences have proven that sometimes drugs inhibiting specific inflammatory pathways failed in JIA, they were found to be efficient in other chronic inflammatory diseases [1].
Over the past decade, the increased therapeutic possibilities resulting in improvement of JIA outcome have changed the way of its definition and classification. The goal for future treatment will be not only to suppress clinical symptoms, as currently, but to achieve an immunologically inactive status. Better understanding of JIA pathogenesis, mechanisms of targeted drug action and identifying biomarkers will be helpful in predicting prognosis, response to treatment and risk of side effects in individual JIA patients. This is the way to achieve personalized strategies for tapering or intensifying therapy in JIA [1, 4–9].

Biomarkers in juvenile idiopathic arthritis


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