hrough 104 weeks or they had the option to continue their double-blind treatment if they maintained a greater than 70% improvement in swollen/tender joint count. Two pre-specified interim analyses at week 24 and week 52 were conducted. The primary endpoint at week 24 was the proportion of patients who achieved an ACR20 response. At weeks 52 and 104, the primary endpoints were change from baseline in modified total Sharp-Genant score and the area under the curve (AUC) of the change from baseline in HAQ-DI score.
Study III eva luated patients with moderate to severe active rheumatoid arthritis who had an inadequate clinical response to MTX. Patients received ACTEMRA 8 mg per kg, ACTEMRA 4 mg per kg, or placebo every four weeks, in combination with MTX (10 to 25 mg weekly). The primary endpoint was the proportion of patients who achieved an ACR20 response at week 24.
Study IV eva luated patients who had an inadequate response to their existing therapy, including one or more DMARDs. Patients received ACTEMRA 8 mg per kg or placebo every four weeks, in combination with the stable DMARDs. The primary endpoint was the proportion of patients who achieved an ACR20 response at week 24.
Study V eva luated patients with moderate to severe active rheumatoid arthritis who had an inadequate clinical response or were intolerant to one or more TNF antagonist therapies. The TNF antagonist therapy was discontinued prior to randomization. Patients received ACTEMRA 8 mg per kg, ACTEMRA 4 mg per kg, or placebo every four weeks, in combination with MTX (10 to 25 mg weekly). The primary endpoint was the proportion of patients who achieved an ACR20 response at week 24.
Clinical Response
The percentages of ACTEMRA-treated patients achieving ACR20, 50 and 70 responses are shown in Table 3. In all studies, patients treated with 8 mg per kg ACTEMRA had higher ACR20, ACR50, and ACR70 response rates versus MTX- or placebo-treated patients at week 24.
During the 24 week controlled portions of Studies I to V, patients treated with ACTEMRA at a dose of 4 mg per kg in patients with inadequate response to DMARDs or TNF antagonist therapy had lower response rates compared to patients treated with ACTEMRA 8 mg per kg.
Table 3 Clinical Response at Weeks 24 and 52 in Active and Placebo Controlled Trials (Percent of Patients) Percent of Patients
Response Rate Study I Study II Study III Study IV Study V
MTX ACTEMRA 8 mg per kg Placebo + MTX ACTEMRA 4 mg per kg + MTX ACTEMRA 8 mg per kg + MTX Placebo + MTX ACTEMRA 4 mg per kg + MTX ACTEMRA 8 mg per kg + MTX Placebo + DMARDs ACTEMRA 8 mg per kg + DMARDs Placebo + MTX ACTEMRA 4 mg per kg + MTX ACTEMRA 8 mg per kg + MTX
N=284 N=286
(95% CI)* N=393 N=399
( 95% CI)* N=398
(95% CI)* N=204 N=213
( 95% CI)* N=205
(95% CI)* N=413 N=803
(95% CI)* N=158 N=161
( 95% CI)* N=170
(95% CI)*
*
CI: 95% confidence interval of the weighted difference to placebo adjusted for site (and disease duration for Study I only)
†
Major clinical response is defined as achieving an ACR 70 response for a continuous 24 week period
ACR20
Week 24 53% 70%
(0.11, 0.27) 27% 51%
(0.17, 0.29) 56%
(0.23, 0.35) 27% 48%
(0.15, 0.32) 59%
(0.23, 0.41) 24% 61%
(0.30, 0.40) 10% 30%
(0.15, 0.36) 50%
(0.36, 0.56)
Week 52 N/A N/A 25% 47%
(0.15, 0.28) 56%
(0.25, 0.38) N/A N/A N/A N/A N/A N/A N/A N/A
ACR50 &nb
