Treatment for Juvenile Rheumatoid Arthritis

Polly Ferguson, M.D.
University of Iowa Department of Pediatrics
First Published: 2003
Last Revised: March 2004
Peer Review Status: Internally Peer Reviewed

History: Juvenile Rheumatoid Arthritis (JRA) is the most common rheumatic condition of childhood. There are three main categories of JRA: pauciarticular, polyarticular, and systemic. The three types differ in the number and distribution of joints involved as well as in the frequency of associated symptoms. The etiology of JRA is unknown, but it appears that a combination of genetic predisposition and environmental triggers are involved.

New facts: Pauciarticular JRA predominantly affects young girls. By definition, four or fewer joints are involved. This group is more likely to have a positive anti-nuclear antibody test and to be at highest risk of developing chronic uveitis. Treatment for pauciarticular disease often involves the use of intraarticular corticosteroid injections, antimalarial drugs, methotrexate, and nonsteroidal anti-inflammatory drugs alone or in combination. Frequent ophthalmologic visits are a necessary part of the treatment plan. Most children have a good response to therapy and a good outcome.

Children with polyarticular JRA have five or more joints inflamed. They typically have a more prolonged and severe course than the pauciarticular patients. Systemic-onset disease may present at any age; high-spiking fevers and a typical salmon-colored rash are the most common presenting features. Systemic symptoms may precede the development of arthritis by months to years. Polyarticular and systemic disease require treatment with a disease-modifying drug, typically methotrexate. Most children improve while taking methotrexate, but many continue to have active synovitis despite treatment.

Practice: Until recently, methotrexate non-responders would be treated with other immunomodulatory drugs, such as cyclosporine or azathioprine, with limited success. However, new anti-cytokine therapies have provided pediatric rheumatologists with a new, effective tool to treat those who fail to respond or only partially respond to conventional therapy. The new therapeutic agents were designed to target specifically small molecules (cytokines) that have been found to play a central role in chronic joint inflammation. The most widely used drugs, such as etanercept, infliximab, and adalimumab, bind tumor necrosis factor (TNF).

To date, the only anti-TNF drug that has been FDA approved to treat children with JRA is etanercept. It is given as a subcutaneous injection twice each week. The dose is 0.4 mg/kg/dose with a maximum of 25 mg/dose. The drug is very effective, but long-term safety is yet to be determined. In the January 2003 volume of Arthritis & Rheumatism, Lovell et al. reported a two-year follow-up study of etanercept treatment in severe, long-standing, methotrexate-resistant polyarticular JRA. The results demonstrate a marked improvement of the condition and a sustained response to treatment (~ 80% met a JRA 50% definition of improvement, DOI, and ~ 70% met the JRA 70% DOI). Etanercept is being used at UI Hospitals and Clinics to treat difficult-to-control or severe polyarticular JRA and to date, all patients have had a marked improvement.

On the down side, there is an increased risk of serious infections while on anti-TNF therapy. Lovell et al. reported two serious infections (n = 43) during the two years of treatment, including one case of varicella with aseptic meningitis and one case of complicated sepsis. Given this risk, the drugs should be used only with extreme caution in patients predisposed to unusual or severe infections or with a history of recurrent infections. Anti-TNF therapy should be discontinued if the patient develops fevers, shaking chills, or other symptoms of infection until the infection is treated and resolved. There have been a few reports of reactivation of latent tuberculosis; therefore, a negative PPD should be documented prior to initiating therapy. Other rare adverse events have included the development of demyelinating diseases and pancytopenia.

Due to the unknown long-term risks, these agents are typically reserved for patients who fail or only partially respond to standard therapy. As the number of individuals treated with anti-TNF agents increases and the safety profile becomes better established, these drugs are likely to be used earlier and earlier in the disease process.

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