Efficacy of Etanercept Shown in Juvenile Rheumatoid Arthritis
In a double-blind, placebo-controlled clinical trial, Lovell etal (NEJM 342(11): 763-769, 2000) found that patients with active polyarticular juvenile rheumatoid arthritis (JRA): experienced significant improvements following treatment with etanercept (Enbrel), a tumor necrosis factor (TNF) inhibitor.
The study design consisted of two parts, an open-label study followed by a double-blind, placebo-controlled study. Patients were between 417 years of age (mean = 10.5), had a mean duration of JRA of 5.9 years, and did not tolerate or had an inadequate response to methotrexate. At base line, all patients had active polyarticular disease defined by the presence of 5 or more swollen joints and 3 or more joints with limitation of motion and pain, tenderness, or both. In Part I, all patients received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to 3 months. By study end, 74% (51 of 69) patients met the definition of improvement defined as a 30% improvement from base line in a at least 3 of 6 response variables; global assessment of the severity of disease by the physician, global assessment of overall well-being by the patient or parent, number of active joints, number of joints with limitation of motion, functional ability, and erythrocyte sedimentation rate. The 51 patients meeting the definition of improvement were then enrolled Part II, the double-blind portion of the study.
In part II, patients were randomly assigned to receive either placebo or 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for 4 months or until a disease flare occurred. Of the patients who received etanercept, 28 % (7 of 25) had a disease flare compared with 81% (21 of 26) of patients who received placebo (p=0.003). The median time to flare was 116 days for patients receiving etanercept and 28 days in the placebo group (p<0.001). By study end, 80′ (20 of 25) of patients who received etanercept still met the definition of improvement, as compared to 35% (9 of 26) of patients who received placebo (p<0.01). The frequency of adverse events did not differ significantly between the two treatment groups.
These data demonstrate that etanercept is effective and well tolerated in pediatric patients with polyarticular JRA.