Abstract

A generation ago, children with arthritis faced a lifetime of pain and disability. Today, there are a multitude of treatment options, including a variety of biologics targeting key cytokines and other inflammatory mediators. While non-steroidal anti-inflammatory drugs and corticosteroids were once the mainstay of therapy, they are now largely used as bridge or adjunctive therapies. Among the conventional disease-modifying anti-rheumatic drugs, methotrexate remains first-line therapy for most children with juvenile idiopathic arthritis (JIA) due to its long track record of safety and effectiveness in the management of peripheral arthritis. Sulfasalazine and leflunomide may also have a secondary role. The tumor necrosis factor inhibitors (TNFi) have shown tremendous benefit in children with polyarticular JIA and likely in enthesitis-related arthritis and psoriatic JIA as well. There may be additional benefit in combining TNFi with methotrexate. Abatacept and tocilizumab also appear to benefit polyarticular JIA; the role of rituximab remains unclear. For the treatment of systemic JIA, while the TNFi are of less benefit, blockade of interleukin-1 or interleukin-6 is highly effective. Additionally, interleukin-1 blockade appears to be effective treatment of macrophage activation syndrome, one of the most dangerous complications of JIA; specifically, anakinra in combination with cyclosporine and corticosteroids may obviate the need for cytotoxic approaches. In contrast, methotrexate along with the TNFi and abatacept are effective agents for the management of uveitis, another complication of JIA. Overall, the biologics have demonstrated an impressive safety record in children with JIA, although children do need to be monitored for rare but potentially dangerous adverse events, such as tuberculosis and other infections; paradoxical development of additional autoimmune diseases; and possibly an increased risk of malignancy. Finally, there may be a window of opportunity during which children with JIA will demonstrate most optimal responses to aggressive therapy, underscoring the need for rapid diagnosis and initiation of treatment.

Highlights

  • A generation ago, children with arthritis were fortunate if they could find a rheumatologist to treat them, and even with the best therapies available at the time, often faced a childhood of pain and disability

  • The role of conventional Disease-modifying anti-rheumatic drug (DMARD) in patients with spondyloarthritis (SpA) is unclear [13], MTX is recommended as initial therapy in all juvenile idiopathic arthritis (JIA) subtypes, following a trial of Nonsteroidal anti-inflammatory drug (NSAID) or Intra-articular CS (IACS) in children with mild oligoarticular JIA [5]

  • A generation ago, a diagnosis of chronic juvenile arthritis relegated children to a lifetime of pain, disability, and dsymorphology, with an increased risk of mortality as well observed in older studies [125]

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Summary

Introduction

A generation ago, children with arthritis were fortunate if they could find a rheumatologist to treat them, and even with the best therapies available at the time, often faced a childhood of pain and disability. An open-label study of etanercept in JIA as well as the German etanercept registry have both shown less of a response in patients with sJIA as compared to those with oligoarticular or polyarticular onset [56,57]. Data is limited to case reports and one case series, which have largely been positive [70,71,72,73,74,75,76] These studies, though limited in numbers and not randomized, do suggest the concerns that rituximab will only be effective in patients with a positive RF may be unfounded, as subjects with multiple JIA categories have responded well. Even in the absence of such a window, the benefits of obtaining rapid control of a potentially debilitating and painful medical condition that may effect growth in young children, whose entire lives are ahead of them, are incontrovertible

Conclusions
49. Zhou H
68. Ohsugi Y
Findings
92. Kimby E
Full Text
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