MANAGEMENT OF JIA IN THE ERA OF BIOLOGICS
Kevin J Murray*
Paediatric rheumatologist Princess Margaret Hospital for Children Perth Western Australia. *
The last 20 years has witnessed a major transformation in the care of children with chronic inflammatory arthritis conditions. Juvenile idiopathic arthritis in its various forms has previously been only partly responsive to treatment in many cases, with chronic pain, joint deformity and damage a common outcome. Most early treatments such as NSAIDs and physical therapies provided only symptomatic control with inevitable progression to joint destruction and disability and a need for joint replacement surgery and life-long disability. The advent of more appropriate and early intensive use of standard disease-modifying agents such as methotrexate and the judicious use of potent longacting intra-articular steroids heralded a major change in prognosis for many children. Almost 60% of polyarticular disease JIA can be maintained in remission now with methotrexate excellent long term outcomes.

So called biological agents have revolutionized medical therapies in many counties in the last 10 years. These agents are the result of vast improvements in understanding the complexities of immune cellular function. The identification of key cytokines or messenger molecules has guided genetic and molecular technologies to design of humanised antibodies and receptor blockers, highly specific for discrete parts of the inflammatory mechanism. Further improvements in disease suppression and even reversal of joint damage have been witnessed. Pioneered by the anti-tumour necrosis factor therapies (Infliximab, etanercept and adalimumab) in the late 1990's the revolution was quickly followed by newer anti-cytokines agents against IL-1 (anakinra) and IL-6 (Tocilizumab/MRA) in particular. All of these therapies have been first used in rheumatoid arthritis in adults but are gaining acceptance and even perhaps more specificity for JIA in some cases.

Specifically anti-TNF therapies have been proven markedly effective in polyarticular course JIA and are recommended for methotrexate resistant, steroid-dependent disease where available. Though etanercept has gained widest acceptance to date, it is likely adalimumab and infliximab will also be important. Despite this advance, some cases are also resistant to anti-TNF therapies particularly the systemic onset form of JIA, known to have the worst prognosis. Most recently IL-1 receptor antagonist treatment (anakinra) and anti-IL6 therapy has been show to be very effective, and even remission inducing in some patients, in initial case series, though controlled trials are lacking. Examples of these responses will be presented.

Anterior uveitis remains a potentially blinding complication of disease and steroid use in some forms of JIA. Use of methotrexate has aided some patients, but complications and visual loss have remained an issue. Recent studies including our own, of the use of Infliximab have been very encouraging in terms of rapid clinical improvement and ability to reduce steroid exposure with recovery of visual loss and prevention of deterioration. Paradoxically etanercept may not only be ineffective but possibly worsen uveitis, indicating the complex nature of these interventions, as well as a need for standardised controlled studies.

Finally previously abandoned agents such as thalidomide are being "re-discovered" for use in auto-immune and malignant disorders including the systemic form of JIA. An example of this use in a child with JIA is also presented.

In summary, the future is very bright for children with JIA. With time much cheaper forms of biological agents will be available with easier and less frequent dosing regimes which can be managed in the home environment.
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