In another study, serum concentration profiles at steady state were comparable among patients with RA treated with 50 mg ENBREL® once weekly and those treated with 25 mg ENBREL® twice weekly. The mean (± standard deviation) Cmax, Cmin, and partial AUC were 2.4 ± 1.5 mcg/mL, 1.2 ± 0.7 mcg/mL, and 297 ± 166 mcg•h/mL, respectively, for patients treated with 50 mg ENBREL® once weekly (N = 21); and 2.6 ± 1.2 mcg/mL, 1.4 ± 0.7 mcg/mL, and 316 ± 135 mcg•h/mL for patients treated with 25 mg ENBREL® twice weekly (N = 16).
Pharmacokinetic parameters were not different between men and women and did not vary with age in adult patients. No formal pharmacokinetic studies have been conducted to examine the effects of renal or hepatic impairment on ENBREL® disposition.
Patients with JIA (ages 4 to 17 years) were administered 0.4 mg/kg of ENBREL® twice weekly for up to 18 weeks. The mean serum concentration after repeated SC dosing was 2.1 mcg/mL, with a range of 0.7 to 4.3 mcg/mL. Limited data suggests that the clearance of ENBREL® is reduced slightly in children ages 4 to 8 years. Population pharmacokinetic analyses predict that administration of 0.8 mg/kg of ENBREL® once weekly will result in Cmax 11% higher, and Cmin 20% lower at steady state as compared to administration of 0.4 mg/kg of ENBREL® twice weekly. The predicted pharmacokinetic differences between the regimens in JIA patients are of the same magnitude as the differences observed between twice weekly and weekly regimens in adult RA patients.
CLINICAL STUDIES
Adult Rheumatoid Arthritis
The safety and efficacy of ENBREL® were assessed in four randomized, double-blind, controlled studies. The results of all four trials were expressed in percentage of patients with improvement in RA using American College of Rheumatology (ACR) response criteria.
Study I eva luated 234 patients with active RA who were ≥ 18 years old, had failed therapy with at least one but no more than four disease-modifying antirheumatic drugs (DMARDs; e.g., hydroxychloroquine, oral or injectable gold, methotrexate [MTX], azathioprine, D-penicillamine, sulfasalazine), and had ≥ 12 tender joints, ≥ 10 swollen joints, and either ESR ≥ 28 mm/hr, CRP > 2.0 mg/dL, or morning stiffness for ≥ 45 minutes. Doses of 10 mg or 25 mg ENBREL® or placebo were administered SC twice a week for 6 consecutive months. Results from patients receiving 25 mg are presented in Table 1.
Study II eva luated 89 patients and had similar inclusion criteria to Study I except that subjects in Study II had additionally received MTX for at least 6 months with a stable dose (12.5 to 25 mg/week) for at least 4 weeks and they had at least 6 tender or painful joints. Subjects in Study II received a dose of 25 mg ENBREL® or placebo SC twice a week for 6 months in addition to their stable MTX dose.
Study III compared the efficacy of ENBREL® to MTX in patients with active RA. This study eva luated 632 patients who were ≥ 18 years old with early (≤ 3 years disease duration) active RA; had never received treatment with MTX; and had ≥ 12 tender joints, ≥ 10 swollen joints, and either ESR ≥ 28 mm/hr, CRP > 2.0 mg/dL, or morning stiffness for ≥ 45 minutes. Doses of 10 mg or 25 mg ENBREL® were administered SC twice a week for 12 consecutive months. The study was unblinded after all patients had completed at least 12 months (and a median of 17.3 months) of therapy. The majority of patients re |
