mained 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 eva luated 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 eva luated ACR response, Sharp radiographic score and safety.
Clinical Response
A higher percentage of patients treated with ENBREL® and ENBREL® in combination with MTX achieved ACR 20, ACR 50, and ACR 70 responses and Major Clinical Responses than in the comparison groups. The results of Studies I, II, and III are summarized in Table 1. The results of Study IV are summarized in Table 2.
Table 1: ACR Responses in Placebo and Active Controlled Trials (Percent of Patients) *
25 mg ENBREL ® SC twice weekly.
†
p < 0.01, ENBREL ® vs. placebo.
‡
p < 0.05, ENBREL ® vs. MTX.
Response Placebo Controlled Active Controlled
Study I Study II Study III
Placebo
N = 80 ENBREL®*
N = 78 MTX/Placebo
N = 30 MTX/ENBREL®*
N = 59 MTX
N = 217 ENBREL®*
N = 207
ACR 20
Month 3 23% 62%† 33% 66%† 56% 62%
Month 6 11% 59%† 27% 71%† 58% 65%
Month 12 NA NA NA NA 65% 72%
ACR 50
Month 3 8% 41%† 0% 42%† 24% 29%
Month 6 5% 40%† 3% 39%† 32% 40%
Month 12 NA NA NA NA 43% 49%
ACR 70
Month 3 4% 15%† 0% 15%† 7% 13%‡
Month 6 1% 15%† 0% 15%† 14% 21%‡
Month 12 NA NA NA NA 22% 25%
Table 2: Study IV Clinical Efficacy Results: Comparison of MTX vs ENBREL ® vs ENBREL ® in Combination with MTX in Patients with RA of 6 Months to 20 Years Duration (Percent of Patients) *
Values are medians.
†
ACR N is the percent improvement based on the same core variables used in defining ACR 20, ACR 50, and ACR 70.
‡
p < 0.05 for comparisons of ENBREL ®/MTX vs ENBREL ® alone or MTX alone.
§
Major clinical response is achieving an ACR 70 response for a continuous 6-month period.
Endpoint MTX
(N = 228) ENBREL® (N = 223) ENBREL®/MTX
(N = 231)
ACR N*†
Month 12 40 47 63‡
ACR 20
Month 12 59% 66% 75%‡
ACR 50
Month 12 36% 43% 63%‡
ACR 70
Month 12 17% 22% 40%‡
Major Clinical Response§ 6% 10% 24%‡
The time course for ACR 20 response rates for patients receiving placebo or 25 mg ENBREL® in Studies I and II is summarized in F |
