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/kg, ACTEMRA 4 mg/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/kg ACTEMRA had statistically significant ACR20, ACR50, and ACR70 response rates versus MTX- or placebo-treated patients at week 24.
Patients treated with ACTEMRA at a dose of 4 mg/kg in patients with inadequate response to DMARDs or TNF antagonist therapy had lower response rates compared to patients treated with ACTEMRA 8 mg/kg.
Table 3 ACR Response at 6 Months in Active and Placebo Controlled Trials (Percent of Patients) Percent of Patients
Response Rate Week 24 Study I Study II Study III Study IV Study V
MTX ACTEMRA 8 mg/kg Placebo + MTX ACTEMRA 4 mg/kg + MTX ACTEMRA 8 mg/kg + MTX Placebo + MTX ACTEMRA 4 mg/kg + MTX ACTEMRA 8 mg/kg + MTX Placebo + DMARDs ACTEMRA 8 mg/kg + DMARDs Placebo + MTX ACTEMRA 4 mg/kg + MTX ACTEMRA 8 mg/kg + MTX
N=284 N=286 N=393 N=399 N=398 N=204 N=213 N=205 N=413 N=803 N=158 N=161 N=170
*
The weighted difference is the difference between ACTEMRA and Placebo response rates, adjusted for site (and disease duration for Study I only).
†
CI: 95% confidence interval of the weighted difference
ACR20
Responders 53% 70% 27% 51% 56% 27% 48% 59% 25% 61% 10% 30% 50%
Weighted Difference %*
(95% CI)† 19
(11, 27) 23
(17, 29) 29
(23, 35) 23
(15, 32) 32
(23, 41) 35
(30, 40) 25
(15, 36) 46
(36, 56)
ACR50
Responders 34% 44% 10% 25% 32% 11% 32% 44% 9% 38% 4% 17% 29%
Weighted Difference % *
(95% CI)† 12
(4, 20) 15
(9, 20) 22
(16, 28) 21
(13, 29) 33
(25, 41) 28
(23, 33) 15
(5, 25) 31
(21, 41)
ACR70
Responders 15% 28% 2% 11% 13% 2% 12% 22% 3% 21% 1% 5% 12%
Weighted Difference % *
(95% CI)† 14
(7, 22) 8
(3, 13) 10
(5, 15) 11
(4, 18) 20
(12, 27) 17
(13, 21) 4
(-6, 13) 12
(3, 22)
The results of the components of the ACR response criteria for Studies III and V are shown in Table 4. Similar results to Study III were observed in Studies I, II and IV.
Table 4 Components of ACR Response at 6 Months Study III Study V
ACTEMRA 4 mg/kg + MTX ACTEMRA 8 mg/kg + MTX Placebo + MTX ACTEMRA 4 mg/kg + MTX ACTEMRA 8 mg/kg + MTX Placebo + MTX
N=213 N=205 N=204 N=161 N=170 N=158
Component (mean) Baseline Week 24* Baseline Week 24 * Baseline Week 24 Baseline Week 24 * Baseline Week 24 * Baseline Week 24
*
Data shown is mean at week 24, difference in adjusted mean change from baseline compared with placebo + MTX at week 24 and 95% confidence interval for that difference
†
Visual analog scale: 0 = best, 100 = worst
‡
Health Assessment Questionnaire: 0 = best, 3 = worst; 20 questions; 8 categories: dressing and grooming, arising, eating, walking |
