BOSTON, Massachusetts—Etanercept (Enbrel®, Amgen/Wyeth Pharmaceuticals) is safe and effective in the long-term treatment of juvenile rheumatoid arthritis (JRA), according to new 8-year outcome data presented at the annual meeting of the American College of Rheumatology in Boston.¹

"We were shocked at how well this stuff worked," said Andreas Reiff, MD, head of the division of rheumatology at the Keck School of Medicine of the University of Southern California and the Children's Hospital Los Angeles. "We had to add an ACR Pediatric (ACR PEDI) 100 because there were patients who had no disease activity and are essentially in remission."

Open-label extension of RCT

The new study was an open-label extension of a double-blind, randomized, controlled trial of etanercept in 69 children with JRA. Overall, 42 patients continued taking etanercept for 4 years, and 26 continued taking the drug for 8 years. Researchers assessed safety and effectiveness in those patients who received at least one dose of etanercept during the open-label extension. Safety assessments included the incidence of serious adverse events, malignancies, lymphomas, and deaths. They analyzed effectiveness using the Childhood Health Assessment Questionnaire (CHAQ), physician global assessment (PhGA), patient's/parent's global assessment (PtGA), number of swollen joints, pain upon movement or limitation in movement, and C-reactive protein (CRP).

The most common reason that patients withdrew from the study was patient/guardian refusal. Nine patients withdrew because of a suboptimal treatment response; five patients withdrew due to adverse effects and another five because of their doctor's decision.

Safety profile looks good

A total of 16 patients (23%) reported 39 serious adverse events. The overall rate of serious adverse events did not increase with long-term exposure to etanercept therapy, the study showed. There were no cases of lupus or demyelinating disorders. The rate of medically important infections was less than the rate reported in a previous study for adult patients with RA.

There were no cases of tuberculosis or other opportunistic infections, but there was one case of pyelonephritis seen in the past 4 years. There were no cases of malignancies or lymphomas seen in this cohort and no deaths were reported.

Etanercept still effective 8 years later

At 7 years, 90% of patients achieved ACR PEDI 30, 90% achieved ACR PEDI  50, 86% achieved ACR PEDI 70, 67% achieved ACR PEDI 90, and 29% achieved ACR PEDI 100. In addition, at 7 years, the median CHAQ was 0.3, the median PhGA was 1.5, the median PtGA was 2, and the median CRP level was 0.1, the study showed.

"Over time patients continue to do better and better and better [on the ACR PEDI]," Dr. Reiff said.

Translating research into practice

"I was pleased to see the etanercept remained safe in those children who were on it for 8 years," said Kathleen A. Haines, MD, section chief of pediatric immunology in the department of pediatric rheumatology and immunology at Hackensack University Medical Center in New Jersey. "However, only a ‘positive' finding of increasing side effects (as disappointing as that would have been) would have given us actionable information. The number of children on etanercept for 8 years is far too few to reveal infrequent long-term effects."

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