Introduction
Materials and methods
Patients
Study design
Endpoints
Sample size
Statistical analysis
Results
Patient disposition and disease characteristics
AMG 108 | |||||
---|---|---|---|---|---|
Placebo (n= 203) | 50 mg (n= 204) | 125 mg (n= 203) | 250 mg (n= 203) | Total (n= 610) | |
Mean age (years) | 52.1 | 51.4 | 51.7 | 52.2 | 51.8 |
Age group, n (%) | |||||
< 65 years | 185 (91.1) | 171 (83.8) | 176 (86.7) | 184 (90.6) | 531 (87.0) |
≥65 years | 18 (8.9) | 33 (16.2) | 27 (13.3) | 19 (9.4) | 79 (13.0) |
Female, n (%) | 158 (77.8) | 155 (76.0) | 163 (80.3) | 160 (78.8) | 478 (78.4) |
Ethnicity, n (%) | |||||
White | 168 (82.8) | 169 (82.8) | 177 (87.2) | 179 (88.2) | 525 (86.1) |
Hispanic | 27 (13.3) | 24 (11.8) | 18 (8.9) | 17 (8.4) | 59 (9.7) |
Othera | 8 (3.9) | 11 (5.4) | 8 (3.9) | 7 (3.4) | 26 (4.3) |
Mean weight (kg) | 76.4 | 77.2 | 74.2 | 75.0 | 75.4 |
Mean height (cm) | 164.0 | 164.6 | 164.0 | 164.8 | 164.5 |
Mean body mass index (kg/m2) | 28.4 | 28.4 | 27.5 | 27.5 | 27.8 |
Mean duration of RA (years) | 7.6 | 7.3 | 7.5 | 8.0 | 7.6 |
Subcomponent of ACR (mean) | |||||
Tender joint count | 26.3 | 26.5 | 24.8 | 26.9 | 26.1 |
Swollen joint count | 16.8 | 16.8 | 15.8 | 15.7 | 16.1 |
Patient global assessment | 5.9 | 6.2 | 6.1 | 6.1 | 6.2 |
Physician global assessment | 6.2 | 6.3 | 6.3 | 6.5 | 6.4 |
Patient pain assessment | 51.2 | 53.9 | 53.5 | 57.0 | 54.8 |
HAQ Disability Index | 1.4 | 1.5 | 1.5 | 1.5 | 1.5 |
C-reactive protein (mg/dl) | 1.2 | 1.8 | 1.5 | 1.4 | 1.6 |
ESR (mm/hour) | 33.4 | 40.1 | 35.6 | 35.5 | 37.1 |
Mean DAS28 CRP | 4.7 | 4.9 | 4.7 | 4.8 | 4.8 |
Mean DAS28 ESR | 5.3 | 5.4 | 5.3 | 5.4 | 5.3 |
Mean tender joint count (28 joints) | 14.0 | 14.5 | 13.5 | 14.0 | 14.0 |
Mean swollen joint count (28 joints) | 11.3 | 10.6 | 10.8 | 11.2 | 11.0 |
Efficacy
AMG 108 | ||||
---|---|---|---|---|
Placebo (n= 203) | 50 mg (n= 204) | 125 mg (n= 203) | 250 mg (n= 203) | |
ACR response, n (%)a | ||||
ACR20 | 59 (29.1) | 63 (30.9) (P = 0.746) | 73 (36.0) (P = 0.168) | 82 (40.4) (P = 0.022) |
ACR50 | 17 (8.4) | 24 (11.8) (P = 0.323) | 28 (13.8) (P = 0.113) | 41 (20.2) (P < 0.001) |
ACR70 | 8 (3.9) | 4 (2.0) (P = 0.259) | 5 (2.5) (P = 0.575) | 12 (5.9) (P = 0.492) |
DAS28 CRP, mean change from baselineb | -0.60 | -0.69 (P = 0.213) | -0.92 (P < 0.001) | -1.18 (P < 0.001) |
EULAR28 response, n (%)c | ||||
Good | 16 (8%) | 20 (10%) | 28 (13.9%) | 39 (19.5%) |
Moderate | 61 (30.7%) | 59 (29.3%) | 76 (37.8%) | 76 (38%) |
No response | 122 (61.3%) | 122 (60.7%) | 97 (48.3%) | 85 (42.5%) |
AMG 108 | ||||
---|---|---|---|---|
Placebo (n= 203) | 50 mg (n= 204) | 125 mg (n= 203) | 250 mg (n= 203) | |
Tender joint count (68 joints) | ||||
Mean (SD) % change | -20.0 (127.5) | -29.5 (60.4) | -35.7 (43.6) | -40.2 (44.3) |
Median % change | -31.3 | -38.4 | -40.0 | -46.7 |
Swollen joint count (66 joints) | ||||
Mean (SD) % change | -32.2 (50.0) | -33.7 (46.5) | -33.8 (114.8) | -39.1 (53.3) |
Median % change | -33.1 | -40.8 | -46.3 | -47.1 |
Patient global assessment | ||||
Mean (SD) % change | -11.6 (49.8) | -16.7 (43.8) | -21.6 (48.2) | -17.8 (64.5) |
Median % change | -20.0 | -16.7 | -28.6 | -20.0 |
Physician global assessment | ||||
Mean (SD) % change | -30.1 (33.7) | -36.0 (30.4) | -36.2 (33.2) | -43.0 (30.8) |
Median % change | -33.3 | -37.5 | -40.0 | -50.0 |
Pain (visual analog scale) | ||||
Mean (SD) % change | 2.2 (142.6) | -11.4 (76.3) | -20.6 (60.6) | -30.9 (46.9) |
Median % change | -12.8 | -20.0 | -28.9 | -34.7 |
HAQ Disability Index | ||||
Mean (SD) % change | -11.1 (53.0) | -12.2 (40.6) | -20.5 (48.2) | -25.2 (44.6) |
Median % change | -11.4 | -13.3 | -20.0 | -25.0 |
Erythrocyte sedimentation rate | ||||
Mean (SD) % change | 12.7 (77.7) | 5 (124.3) | -18.3 (68.7) | -30.4 (73.7) |
Median % change | -6.3 | -13.2 | -36.8 | -46.7 |
C-reactive protein | ||||
Mean (SD) % change | 123.2 (695.3) | 32.2 (164.0) | -1.9 (181.5) | -25.5 (168.5) |
Median % change | 5.1 | -12.4 | -41.2 | -59.4 |
Tender joint count (28 joints) | ||||
Mean (SD) % change | -13.2 (143.7) | -21.0 (73.2) | -31.6 (58.7) | -36.5 (65.7) |
Median % change | -33.3 | -33.3 | -40.0 | -44.4 |
Swollen joint count (28 joints) | ||||
Mean (SD) % change | -28.2 (52.7) | -30.0 (48.1) | -28.7 (118.3) | -38.0 (52.2) |
Median % change | -33.3 | -33.3 | -44.4 | -44.4 |
Pharmacokinetics
50 mg AMG 108 | 125 mg AMG 108 | 250 mg AMG 108 | ||||
---|---|---|---|---|---|---|
Week 20 (n= 144) | Week 24 (n= 137) | Week 20 (n= 146) | Week 24 (n= 140) | Week 20 (n= 137) | Week 24 (n= 138) | |
Mean | 0 | 0 | 16.5 | 19.8 | 155 | 160 |
Median | 0 | 0 | 6.25 | 4.65 | 139 | 141 |
Range | 0 to 6.43 | 0 to 0.32 | 0 to 104 | 0 to 268 | 0 to 417 | 0 to 1,000 |
Safety
AMG 108 | |||||
---|---|---|---|---|---|
Placebo (n= 201) | 50 mg (n= 202) | 125 mg (n= 201) | 250 mg (n= 201) | Totala (n= 604) | |
Any AE | 133 (66.2) | 134 (66.3) | 143 (71.1) | 135 (67.2) | 412 (68.2) |
Most common AE | |||||
Headache | 16 (8.0) | 11 (5.4) | 15 (7.5) | 15 (7.5) | 41 (6.8) |
Diarrhea | 13 (6.5) | 10 (5.0) | 11 (5.5) | 15 (7.5) | 36 (6.0) |
Nasopharyngitis | 18 (9.0) | 11 (5.4) | 13 (6.5) | 12 (6.0) | 36 (6.0) |
URI | 15 (7.5) | 10 (5.0) | 13 (6.5) | 13 (6.5) | 36 (6.0) |
Treatment-related AE | 48 (23.9) | 43 (21.3) | 50 (24.9) | 45 (22.4) | 138 (22.8) |
AE leading to: | |||||
Study discontinuation | 1 (0.5) | 3 (1.5) | 3 (1.5) | 3 (1.5) | 9 (1.5) |
Withdrawal of study drug | 2 (1.0) | 4 (2.0) | 4 (2.0) | 3 (1.5) | 11 (1.8) |
Hospitalization | 9 (4.5) | 5 (2.5) | 5 (2.5) | 6 (3.0) | 16 (2.6) |
Any infection | 72 (35.8) | 64 (31.7) | 68 (33.8) | 62 (30.8) | 194 (32.1) |
Infection leading to: | |||||
Study discontinuation | 1 (0.5) | 0 | 0 | 1 (0.5) | 1 (0.2) |
Withdrawal of study drug | 0 | 1 (0.5) | 0 | 1 (0.5) | 2 (0.3) |
Hospitalization | 3 (1.5) | 1 (0.5) | 1 (0.5) | 2 (1.0) | 4 (0.7) |
Injection site reaction | 5 (2.5) | 8 (4.0) | 10 (5.0) | 9 (4.5) | 27 (4.5) |
Any serious AE | 11 (5.5) | 6 (3.0) | 6 (3.0) | 9 (4.5) | 21 (3.5) |
Treatment-related serious AE | 2 (1.0) | 2 (1.0) | 1 (0.5) | 1 (0.5) | 4 (0.7) |
Serious infection | 3 (1.5) | 2 (1.0) | 1 (0.5) | 2 (1.0) | 5 (0.8) |
Death | 0 | 0 | 0 | 0 | 0 |