Response to MTX)*
* The same patients may not have responded at each timepoint.
Figure 1
Radiographic Response
In Study II, structural joint damage was assessed radiographically and expressed as change in total Sharp-Genant score and its components, the erosion score and joint space narrowing score. Radiographs of hands/wrists and forefeet were obtained at baseline, 24 weeks, 52 weeks, and 104 weeks and scored by readers unaware of treatments group and visit number. The results from baseline to week 52 are shown in TABLE 6. ACTEMRA 4 mg per kg slowed (less than 75% inhibition compared to the control group) and ACTEMRA 8 mg per kg inhibited (at least 75% inhibition compared to the control group) the progression of structural damage compared to placebo plus MTX at week 52.
Table 6 Mean Radiographic Change from Baseline to Week 52 in Study II
Placebo + MTX ACTEMRA 4 mg per kg + MTX ACTEMRA 8 mg per kg + MTX
N=294 N=343 N=353
SD = standard deviation
* Week 52 analysis employs linearly extrapolated data for patients after escape, withdrawal, or loss to follow up. † Difference between the adjusted means (ACTEMRA + MTX - Placebo + MTX)
Week 52*
Total Sharp-Genant Score, Mean (SD) 1.17
(3.14) 0.33
(1.30) 0.25
(0.98)
Adjusted Mean difference†
(95%CI) -0.83
(-1.13, -0.52) -0.90
(-1.20, -0.59)
Erosion Score, Mean (SD) 0.76
(2.14) 0.20
(0.83) 0.15
(0.77)
Adjusted Mean difference†
(95%CI) -0.55
(-0.76, -0.34) -0.60
(-0.80, -0.39)
Joint Space Narrowing Score, Mean (SD) 0.41
(1.71) 0.13
(0.72) 0.10
(0.49)
Adjusted Mean difference†
(95%CI) -0.28
(-0.44, -0.11) -0.30
(-0.46, -0.14)
The mean change from baseline to week 104 in Total Sharp-Genant Score for the ACTEMRA 4 mg per kg groups was 0.47 (SD = 1.47) and for the 8 mg per kg groups was 0.34 (SD = 1.24). By the week 104, most patients in the control (placebo + MTX) group had crossed over to active treatment, and results are therefore not included for comparison. Patients in the active groups may have crossed over to the alternate active dose group, and results are reported per original randomized dose group.
In the placebo group, 66% of patients experienced no radiographic progression (Total Sharp-Genant Score change ≤ 0) at week 52 compared to 78% and 83% in the ACTEMRA 4 mg per kg and 8 mg per kg, respectively. Following 104 weeks of treatment, 75% and 83% of patients initially randomized to ACTEMRA 4 mg per kg and 8 mg per kg, respectively, experienced no progression of structural damage compared to 66% of placebo treated patients.
Health Related Outcomes
In Study II, physical function and disability were assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI). Both dosing groups of ACTEMRA demonstrated a greater improvement compared to the placebo group in the AUC of change from baseline in the HAQ-DI through week 52. The mean change from baseline to week 52 in HAQ-DI was 0.6, 0.5, and 0.4 for ACTEMRA 8 mg per kg, ACTEMRA 4 mg per kg, and placebo treatment groups, respectively. Sixty-three percent (63%) and sixty percent (60%) of patients in the ACTEMRA 8 mg per kg and ACTEMRA 4 mg per kg treatment groups, respectively, achieved a clinically relevant improvement in HAQ-DI (change from bas |
