Etanercept appears to maintain its safety through 8 years of continuous use in children with polyarticular-course juvenile rheumatoid arthritis without any incidence of cancers or serious opportunistic infections.
That is the conclusion reached by investigators of a multicenter, randomized, controlled trial that was later extended into an open-label study that specifically examined the long-term safety of the anti-tumor necrosis factor-α drug.
“Etanercept [Enbrel] was the first of the anti-TNF agents tested in children with JRA, and thus we have the longest and most clinical experience with it. This study, although small, was very reassuring,” said Dr. Daniel Lovell of the Cincinnati Children's Hospital Medical Center, in an interview.
It is indicated for reducing the signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis (JRA) in those who have had an inadequate response to one or more disease-modifying antirheumatic drugs.
Of 69 patients who were originally randomized into the trial, Dr. Lovell and Dr. Andreas Reiff and their colleagues followed 58 patients into the open-label extension; all the patients had taken at least one dose of etanercept. Dr. Reiff originally presented the follow-up data at the annual European Congress of Rheumatology in Barcelona.
In the original randomized trial, all of the patients initially received etanercept for 3 months. Those who responded to the drug remained in the study and were randomized to either etanercept or placebo. Corticosteroids and anti-inflammatory drugs were allowed during both the randomized trial and the open-label extension, but relatively few patients were allowed to begin taking methotrexate again, said Dr. Reiff, head of the division of rheumatology and rehabilitation at Children's Hospital Los Angeles.
In the ongoing safety study, 42 of the original patients (61%) received at least 4 years of etanercept, and 16 (23%) received at least 8 continuous years of the study drug. They used the recommended dosage on the label of the subcutaneous injection formulation (0.4 mg/kg twice a week).
Overall, 16 patients (23%) reported adverse events. Long-term use did not significantly increase the rate of adverse events. Between years 4 to 8 of the follow-up period, only one severe adverse event (pyelo- nephritis) occurred. No cases of lupus; demyelinating disorders; tuberculosis or other opportunistic infections; or malignancy were reported. No deaths were reported.
Three cases of varicella infection occurred during follow-up, said Dr. Reiff. Although Dr. Lovell said that overall etanercept had a very good safety profile, he expressed caution about an increased risk of varicella in children on etanercept who lack protective antibodies to this virus.
Dr. Lovell suggested all children be tested for varicella antibodies before starting treatment with etanercept and that extra precautions be taken to avoid exposing nonimmune children taking etanercept to others with active varicella disease.
Dr. Reiff serves as an adviser and speaker for Amgen Inc. and Wyeth, which comarket etanercept in North America.
All children should be tested for varicella antibodies before starting treatment with etanercept. DR. LOVELL