Table 2.
Overall adverse events
| n (%) | Placebo → 50 mg q4w n=305 |
Placebo → 100 mg q2w n=291 |
50 mg q4w Start n=605 |
100 mg q2w Start n=619 |
50 mg q4w Combined n=910 |
100 mg q2w Combined n=910 |
Combined N=1820 |
| Patients with ≥1 TEAE | 233 (76.4) | 234 (80.4) | 483 (79.8) | 489 (79.0) | 716 (78.7) | 723 (79.5) | 1439 (79.1) |
| Serious AEs | 65 (21.3) | 81 (27.8) | 160 (26.4) | 143 (23.1) | 225 (24.7) | 224 (24.6) | 449 (24.7) |
| Serious AEs occurring in >10 patients overall | |||||||
| Pneumonia | 4 (1.3) | 8 (2.7) | 9 (1.5) | 19 (3.1) | 13 (1.4) | 27 (3.0) | 40 (2.2) |
| Cellulitis | 3 (1.0) | 4 (1.4) | 12 (2.0) | 10 (1.6) | 15 (1.6) | 14 (1.5) | 29 (1.6) |
| Osteoarthritis | 2 (0.7) | 9 (3.1) | 3 (0.5) | 9 (1.5) | 5 (0.5) | 18 (2.0) | 23 (1.3) |
| Sepsis | 1 (0.3) | 6 (2.1) | 3 (0.5) | 5 (0.8) | 4 (0.4) | 11 (1.2) | 15 (0.8) |
| Rheumatoid arthritis | 0 | 2 (0.7) | 6 (1.0) | 5 (0.8) | 6 (0.7) | 7 (0.8) | 13 (0.7) |
| Leading to discontinuation | 27 (8.9) | 35 (12.0) | 62 (10.2) | 69 (11.1) | 89 (9.8) | 104 (11.4) | 193 (10.6) |
| Cellulitis | 0 | 2 (0.7) | 3 (0.5) | 3 (0.5) | 3 (0.3) | 5 (0.5) | 8 (0.4) |
| Diverticulitis | 2 (0.7) | 2 (0.7) | 0 | 2 (0.3) | 3 (0.3) | 4 (0.4) | 7 (0.4) |
| Pneumonia | 0 | 2 (0.7) | 1 (0.2) | 4 (0.6) | 1 (0.1) | 6 (0.7) | 7 (0.4) |
| Sepsis | 0 | 2 (0.7) | 1 (0.2) | 4 (0.6) | 1 (0.1) | 6 (0.7) | 7 (0.4) |
| Thrombocytopenia | 0 | 2 (0.7) | 0 | 4 (0.6) | 0 | 6 (0.7) | 6 (0.3) |
| AEs of interest | |||||||
| Deaths | 5 (1.6) | 6 (2.1) | 13 (2.1) | 8 (1.3) | 18 (2.0) | 14 (1.5) | 32 (1.8) |
| Malignancies | 3 (1.0) | 10 (3.4) | 9 (1.5) | 11 (1.8) | 12 (1.3) | 21 (2.3) | 33 (1.8) |
| Hepatobiliary abnormalities* | 0 | 1 (0.3) | 1 (0.2) | 1 (0.2) | 1 (0.1) | 2 (0.2) | 3 (0.2) |
| MACE | 6 (2.0) | 2 (0.7) | 14 (2.3) | 7 (1.1) | 20 (2.2) | 9 (1.0) | 29 (1.6) |
| MI | 1 (0.3) | 0 | 2 (0.3) | 3 (0.5) | 3 (0.3) | 3 (0.3) | 6 (0.3) |
| Stroke | 3 (1.0) | 2 (0.7) | 5 (0.8) | 3 (0.5) | 8 (0.9) | 5 (0.5) | 13 (0.7) |
| Gastrointestinal perforations | 2 (0.7) | 4 (1.4) | 4 (0.7) | 3 (0.5) | 6 (0.7) | 7 (0.8) | 13 (0.7) |
| Injection-site reactions | 11 (3.6) | 27 (9.3) | 23 (3.8) | 41 (6.6) | 34 (3.7) | 68 (7.5) | 102 (5.6) |
| Demyelination | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hypersensitivity reaction or serum sickness AE | 1 (0.3) | 2 (0.7) | 1 (0.2) | 2 (0.3) | 2 (0.2) | 4 (0.4) | 6 (0.3) |
| Deep vein thrombosis | 3 (1.0) | 2 (0.7) | 4 (0.7) | 4 (0.6) | 7 (0.8) | 6 (0.7) | 13 (0.7) |
| Thrombosis† | 0 | 0 | 0 | 1 (0.2) | 0 | 1 (0.1) | 1 (0.1) |
*Hepatobiliary abnormalities defined as occurrence of any of the following: (1) ALT or AST≥8× ULN; (2) ALT or AST≥5× ULN for ≥2 weeks; (3) ALT or AST≥3× ULN and total bilirubin ≥2× ULN; (4) ALT or AST≥3× ULN accompanied by clinical symptoms believed to be related to hepatitis or hypersensitivity (eg, new or worsening of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever or rash) and (5) ALT or AST≥5× ULN but <8× ULN and cannot be monitored at least weekly for ≥2 weeks.
†Thrombosis other than deep vein thrombosis.
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; MACE, major adverse cardiovascular events; MI, myocardial infarction; q2w, every 2 weeks; q4w, every 4 weeks; TEAE, treatment-emergent adverse event; ULN, upper limit of normal.