d treatment with MTX,and had ≥ 12 tender joints, ≥ 10 swollen joints, and either ESR ≥ 28 mm/hr, CRP > 2.0 mg/dL, or morning stiffnessfor ≥ 45 minutes. Doses of 10 mg or 25 mg etanercept 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 etanercept. MTX tablets (escalated from7.5 mg/week to a maximum of 20 mg/week over the first 8 weeks of the trial) or placebo tablets were given once aweek on the same day as the injection of placebo or etanercept 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 aninadequate response to at least one DMARD other than MTX. Forty-three percent of patients had previously receivedMTX for a mean of 2 years prior to the trial at a mean dose of 12.9 mg. Patients were excluded from this study ifMTX had been discontinued for lack of efficacy or for safety considerations. The patient baseline characteristics weresimilar to those of patients in Study I. Patients were randomized to MTX alone (7.5 to 20 mg weekly, dose escalatedas described for Study III; median dose 20 mg), etanercept alone (25 mg twice weekly), or the combination ofetanercept and MTX initiated concurrently (at the same doses as above). The study eva luated ACR response, Sharpradiographic score, and safety.
Clinical Response
A higher percentage of patients treated with etanercept and etanercept 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 StudiesI, II, and III are summarized in Table 6. The results of Study IV are summarized in Table 7.
Table 6. ACR Responses in Placebo- and Active-Controlled Trials
(Percent of Patients)
Response
Placebo Controlled Active Controlled
Study I Study II Study III
Placebo
N=80
Etanercepta
N=78
MTX/Placebo
N=30
MTX/Etanercepta
N=59
MTX
N=217
Etanercepta
N=207
ACR 20
Month 3
Month 6
Month 12
23%
11%
NA
62%b
59%b
NA
33%
27%
NA
66% b
71% b
NA
56%
58%
65%
62%
65%
72%
ACR 50
Month 3
Month 6
Month 12
8%
5%
NA
41%b
40%b
NA
0%
3%
NA
42% b
39% b
NA
24%
32%
43%
29%
40%
49%
ACR 70
Month 3
Month 6
Month 12
4%
1%
NA
15%b
15%b
NA
0%
0%
NA
15%b
15%b
NA
7%
14%
22%
13%c
21%c
25% a 25 mg etanercept SC twice weekly
b p < 0.01, etanercept vs placebo c p < 0.05, etanercept vs MTX
Table 7. Study IV Clinical Efficacy Results: Comparison of MTX vs Etanercept vs Etanercept in CombinationWith MTX in Patients With Rheumatoid Arthritis of 6 Months to 20 Years Duration(Percent of Patients)
Endpoint
MTX
(N=228)
Etanercept
(N=223)
Etanercept/MTX
(N=231)
ACR Na, b
Month 12 40% 47% 63%c
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, andACR 70.
c p < 0.05 for comparisons of etanercept/MTX vs etanercept
