Enbrel - Clinical Pharmacology

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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)

Placebo Controlled Active Controlled

Study I Study II Study III

Placebo ENBREL®a MTX/

Placebo

MTX/

ENBREL®a

MTX ENBREL®a

Response N = 80 N = 78 N = 30 N = 59 N = 217 N = 207

ACR 20

Month 3 23% 62%b 33% 66%b 56% 62%

Month 6 11% 59%b 27% 71%b 58% 65%

Month 12 NA NA NA NA 65% 72%

ACR 50

Month 3 8% 41%b 0% 42%b 24% 29%

Month 6 5% 40%b 3% 39%b 32% 40%

Month 12 NA NA NA NA 43% 49%

ACR 70

Month 3 4% 15%b 0% 15%b 7% 13%c

Month 6 1% 15%b 0% 15%b 14% 21%c

Month 12 NA NA NA NA 22% 25%

a 25 mg ENBREL® SC twice weekly.

b p < 0.01, ENBREL® vs. placebo.

c p < 0.05, ENBREL® vs. MTX.

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)

Endpoint

MTX

(N = 228)

ENBREL®

(N = 223)

ENBREL®/MTX

(N = 231)

ACR Na, b

Month 12 40 47 63c

ACR 20

Month 12 59% 66% 75%c

ACR 50

Month 12 36% 43% 63%c

ACR 70

Month 12 17% 22% 40%c

Major Clinical Responsed 6% 10% 24%c

a Values are medians.

b ACR N is the percent improvement based on the same core variables used in defining ACR 20, ACR

50 and ACR 70.

c p < 0.05 for comparisons of ENBREL®/MTX vs ENBREL® alone or MTX alone.

d Major clinical response is achieving an ACR 70 response for a continuous 6 month period.

The time course for ACR 20 response rates for patients receiving placebo or 25 mg ENBREL® in

Studies I and II is summarized in Figure 1. The time course of responses to ENBREL® in Study

III was similar.

Percent Responding

0

10

20

30

40

50

60

70

80

Months

0 1 2 3 4 5 6

Figure 1:

Time Course of ACR 20 Responses

25 mg ENBREL®, Study II (ENBREL® + MTX)

25 mg ENBREL®, Study I (ENBREL® alone) Placebo, Study I (placebo alone)