Enbrel - Clinical Pharmacology

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Study II evaluated 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 evaluated 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 remained in the study on the treatment to which they were randomized through 2 years, after which they entered an extension study and received open-label 25 mg ENBREL®. Results from patients receiving 25 mg are presented in Table 1. MTX tablets (escalated from 7.5 mg/week to a maximum of 20 mg/week over the first 8 weeks of the trial) or placebo tablets were given once a week on the same day as the injection of placebo or ENBREL® doses, respectively.

Study IV evaluated 682 adult patients with active RA of 6 months to 20 years duration (mean of 7 years) who had an inadequate response to at least one DMARD other than MTX. Forty-three percent of patients had previously received MTX a mean of two years prior to the trial at a mean dose of 12.9 mg. Patients were excluded from this study if MTX had been discontinued for lack of efficacy or for safety considerations. The patient baseline characteristics were similar to those of patients in Study I (Table 3). Patients were randomized to MTX alone (7.5 to 20 mg weekly, dose escalated as described for Study III; median dose 20 mg), ENBREL® alone (25 mg twice weekly), or the combination of ENBREL® and MTX initiated concurrently (at the same doses as above). The study evaluated ACR response, Sharp radiographic score and safety.