Juvenile rheumatoid arthritis

The most common rheumatologic condition in children is juvenile rheumatoid arthritis (JRA). About one third of children can be treated effectively with nonsteroidal anti-inflammatory drugs (NSAIDs). However, more than one half require more aggressive therapy. The second-line drug of choice has been methotrexate. Although effective, it requires close monitoring, and side effects increase with dosage increases. Etanercept is a novel, genetically developed agent that has proved effective for treating rheumatoid arthritis in adults. This drug selectively inhibits the activity of tumor necrosis factor, an inflammatory cytokine that is believed to play a role in the pathogenesis of rheumatoid arthritis. Lovell and colleagues performed a randomized, double-blind trial of etanercept in the treatment of polyarticular JRA.

Children enrolled in the trial were between four and 17 years of age and had active polyarticular JRA. Active disease was defined as having five or more swollen joints and three or more with pain, tenderness or decreased range of motion. Treatment with NSAIDs or methotrexate had failed in all of the children before entering the study.

The patients were initially given subcutaneous injections of etanercept twice a week for up to three months as the first part of the trial. After three months, the children that improved (based on a core set of six defined variables) were randomized to continue etanercept therapy or to receive twice-weekly injections of placebo. The second phase of the trial lasted four months. Regular clinical and serologic assessments were maintained throughout the study, and all children were evaluated for adverse effects from the drug. The primary end point of the study was the number of patients who had a flare of JRA.

Sixty-nine children were enrolled in the open-label study, and 51 (74 percent) had an acceptable response and were randomized into the double-blind phase of the study. The average age of the children was 10.5 years. In the double-blind study, seven of 25 children who received etanercept had disease flare compared with 21 of 26 who were given placebo. The median time to flare of JRA was 28 days in the placebo group and 116 days in the children maintained on the study drug. After seven months, 80 percent of the etanercept group and 35 percent of the placebo group met the study criteria for improvement. Significant declines in erythrocyte sedimentation rates, C-reactive protein level, white cell counts and platelet counts were noted in children who received etanercept.

With regard to the safety of etanercept, one child had an urticarial reaction and two children were hospitalized for serious adverse events (depression and gastroenteritis-influenza syndrome). In the open-label study, the most common events were injection site reactions, upper respiratory infections and headache. There were no deaths in either arm of the trial. Fifty-nine of the eligible children continued taking the drug as part of an open-label, extended treatment study.

The authors conclude from this study that etanercept is a safe and effective option for the treatment of children with polyarticular juvenile rheumatoid arthritis.

COPYRIGHT 2000 American Academy of Family Physicians
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