Treatment of juvenile idiopathic arthritis: a revolution in care

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.

Effective Use of Monoclonal Antibodies Against TNF — Adalimumab — As a Switchover Drug in a Patient With Juvenile Idiopathic Polyarthritis and Uveitis

“…Использование ГИБП, действие которых направлено на подавление эффектов цитокинов, а также других фак-торов, участвующих в воспалении, имело революционное значение для терапии ревматических заболеваний [9][10][11]. По данным немногочисленных исследований, эффек-тивность ГИБП, преимущественно ингибиторов фактора некроза опухоли (tumor necrosis factor, TNF) ␣, значительно варьирует у детей с увеитами и составляет от 35 до 100%, что обусловлено различием критериев отбора больных, успеха терапии, сроков наблюдения, сопутствующего лече-ния, малым числом пациентов [12][13][14].…”

Treatment in juvenile rheumatoid arthritis and new treatment options

“…In addition, the patient's preference should be considered in terms of the mode of administration and frequency of administration. The limitations for use of these drugs include inadequate long-term safety data and cost, though they are efficient drugs (1)(2)(3)(11)(12)(13)(14).…”

“…Treatment in JRA findings improve in time. When repeated intraarticular steroid injection is required for the same joint, a period of 3-4 months should have passed (1)(2)(3)13).…”

“…It is not recommended to be used in systemic JIA, since the risk of side effects is increased. The initial dose is 10-20 mg/kg/day and the dose is increased to 30-50 mg/kg/day in weeks (1)(2)(3)(11)(12)(13)(14).…”

“…ACR Pedi; American College of Rheumatology Pediatric; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; JIA: juvenile idiopathic arthritis; JADAS: Juvenile Arthritis Disease decreased complaints and physical findings. In rare cases, a single high dose of 30mg/kg steroid may be administered parenterally to supress severe systemic disease and this dose may be repeated when necessary (1)(2)(3)13).…”