CINCINNATI, Ohio—Long-term, continuous treatment with etanercept (Enbrel^®, Immunex Corp) was safe and remained effective for at least 8 years in children with juvenile rheumatoid arthritis (JRA), according to researchers from the Pediatric Rheumatology Collaborative Study Group, which includes over 70 pediatric rheumatology centers in the US and Canada.

Reporting for the investigators, Daniel J. Lovell, MD, MPH, of Cincinnati Children’s Hospital Medical Center in Ohio, wrote in Arthritis & Rheumatism, “The results of the present study show that in this population of patients with JRA, long-term continuous treatment with etanercept was well tolerated for up to 8 years, without an increase in the rates of SAEs (serious adverse events) over time. In addition, these data demonstrate that continuous treatment with etanercept resulted in sustained improvements in clinically important signs and symptoms of JRA for up to 8 years.”¹

Open-label extension of major etanercept randomized clinical trial

The 58 patients in the study were among 69 who had previously participated in a randomized controlled trial of the drug and had a total of 318 patient-years of etanercept exposure. Median age at baseline was 10 years, and median disease duration was 5.9 years. All had polyarticular JRA that had not been adequately controlled on methotrexate (MTX) or other disease-modifying drugs (DMARDs). A total of 42 (72%) of the 58 patients entered the fourth year of continuous etanercept treatment, 26 (45%) entered the eighth year.

Treatment with MTX and other DMARDs was discontinued a minimum of 2 weeks before enrollment, although maintaining a low-dose regimen of corticosteroids or NSAIDs was allowed. The treatment regimen was based on the patient’s body weight, with a maximum weekly dosage of 50 mg. Patients in the extension study were permitted to add low-dose MTX if recommended by their physician. Response was assessed every 3 months during the first year of the extension phase, then every 4 to 6 months.

Safety endpoints were the incidences of SAEs medically important infections (MIIs), and death. Efficacy endpoints were the American College of Rheumatology (ACR) Pediatric (Pedi) -30, -50, -70, -90, and -100 response criteria.

The 8-year analysis found the following:

• Overall exposure-adjusted SAE rate of 0.12 events per patient-year
• No increase in SAEs with long-term exposure to etanercept
• Overall exposure-adjusted MII rate of 0.03 events per patient year
• No increase in MIIs with long-term exposure to etanercept
• No cases of tuberculosis
• No cases of lupus
• No malignancies
• No nervous system disorders
• No deaths
• JRA flare was the most common AE
• 100% ACR, Pedi 70 responses in patients who had received 8 years’ worth of weekly etanercept

“Continuous treatment with etanercept resulted in truly important, often profound, sustained improvement in all aspects of this disease including clinically important signs and symptoms of JRA, improvements in functional ability and decreased pain for up to 8 years,” Dr. Lovell said.

Translating research into practice

Thomas J. A. Lehman MD, chief of the division of pediatric rheumatology at the Hospital for Special Surgery, and professor of clinical pediatrics at Cornell University’s Weill Medical Center in New York, told MSKreport.com, “Etanercept has been very safe in children and the study confirms the absence of unusual or worrisome late side effects that some parents feared. The increasing evidence of etanercept’s safety makes it clear that early and aggressive treatment of children with severe arthritis will improve the outcome without an undue risk.”

According to Dr. Lehman, the major unanswered question about etanercept in JRA is for how long to continue the TNF inhibitors once the child looks well. “We don’t yet know how often we will be able to take the drug away without problems versus the children whose arthritis will come back again when we withdraw the TNF inhibitor.”

Reference

1. Lovell DJ, Reiff A, Ilowite NT, et al. Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum. 2008;58:1496-1504.