SAN FRANCISCO—Long-term continuous treatment with etanercept (Enbrel^®, Amgen Wyeth) is both safe and effective for children with juvenile rheumatoid arthritis (JRA), experts reported at the American College of Rheumatology 2008 meeting.¹ This industry-funded report is expected to provide some level of reassurance to clinicians and families concerned about potential risks associated with long-term use of biological agents in these young patients.

Few serious problems reported in over 1200 patient-years of exposure

“Serious adverse events and medically important infections were prospectively and systematically collected in 594 patients representing over 1200 years of exposure. These data suggest that etanercept, alone or in combination with methotrexate, is safe as long-term continuous therapy for the treatment of juvenile rheumatoid arthritis,” said coinvestigator Norman T. Ilowite, MD. Dr. Ilowite is chief of rheumatology at Children's Hospital, Einstein College of Medicine, in the Bronx, New York.

Researchers in this multicenter study examined data from a 3-year, open label nonrandomized registry of children with either polyarticular or systemic onset juvenile rheumatoid arthritis who were treated with methotrexate (MTX), etanercept (ETN), or both in combination. The primary study objective was to determine safety of these approaches used in this population for up to 3 years.

Inclusion criteria were patients, age 2 to 18 years, with a diagnosis of polyarticular or systemic JRA and a history of treatment with MTX (n=198), ETN (n=105), or MTX/ETN in combination (n=299). Coadministration of nonbiologic DMARDs was allowed. In addition, patients initially treated with MTX could switch to the ETN or MTX/ETN arms within 30 months.

Doses and administration schedules were: ETN sc twice weekly at 0.4 mg/kg (maximum dose of 25 mg) or once weekly at 0.8 mg/kg (maximum dose 50 mg); MTX at ≥10 mg/m2/wk (not to exceed 1 mg/kg/wk). The investigators monitored incidence of serious adverse events (SAEs), medically important infections (MIIs), mortality, joint counts, and Physician’s Global Assessment (PhGA).

A total of 66 (33%), 33 (31%), and 105 (35%) patients from the MTX, ETN, and MTX/ETN groups have completed the 3-year registry. This report included patient-years of exposure of 388 for MTX, 210 for ETN, and 610 for MTX/ETN. None of the MTX patients, 14% of the ETN patients, and 12% of the MTX/ETN patients are still on treatment and in the registry.

“Withdrawals from the study included 36 (18%), 8 (8%), and 55 (19%) patients who discontinued due to insufficient therapeutic effect, 3 (2%), 2 (2%), and 1 (0.3%) who discontinued due to AEs, and 24 (12%), 8 (8%), and 11 (4%) who discontinued due to remission,” the investigators reported. Rates of SAEs per 100 patient-years were 4.4 for MTX, 7.6 for ETN, and 5.7 for MTX/ETN. Rates of MII per 100 patient-years were 1.3 for MTX, 1.9 for ETN, and 2.1 for MTX/ETN.

The researchers found one case of lupus with MTX and 2 cases of sepsis: 1 with ETN and 1 with MTX/ETN.

Importantly, there were no cases of lymphoma, other malignancy, tuberculosis, or death. “Improvements in outcome measures for all groups were similar and maintained for 36 months,” the investigators reported.

They conclude, “These data suggest etanercept is safe as a long-term, continuous therapy for treatment of JRA.”

Reference

1. Giannini EH, Ilowite NT, Lovell DJ, et al. Safety data from over 1,200 patients-years of methotrexate and/or etanercept treatment in children with polyarticular or systemic juvenile rheumatoid arthritis. Presented at American College of Rheumatology 2008 meeting. San Francisco, CA; October 28, 2008. Presentation 1496.