Summary of safety findings (safety population)
| Placebo+MTX n=282 | 4 mg/kg TCZ+MTX n=289 | 8 mg/kg TCZ+MTX n=290 | 8 mg/kg TCZ+placebo n=292 | |
|---|---|---|---|---|
| Patients with one or more event, n (%) | ||||
| Any AEs | 235 (83.3) | 256 (88.6) | 256 (88.3) | 250 (85.6) |
| Infections | 136 (48.2) | 155 (53.6) | 137 (47.2) | 138 (47.3) |
| AEs resulting in premature withdrawal from the study | 21 (7.4) | 35 (12.1) | 59 (20.3) | 34 (11.6) |
| Any SAEs | 24 (8.5) | 29 (10.0) | 31 (10.7) | 25 (8.6) |
| SAEs of special interest | ||||
| Infections | 6 (2.1) | 11 (3.8) | 10 (3.4) | 8 (2.7) |
| Malignancies | 3 (1.1) | 4 (1.4) | 1 (0.3) | 2 (0.7) |
| Myocardial infarctions | 0 | 3 (1.0) | 1 (0.3) | 1 (0.3) |
| Strokes | 2 (0.7) | 2 (0.7) | 0 | 0 |
| Hypersensitivity reactions | 0 | 1 (0.3) | 0 | 1 (0.3) |
| Gastrointestinal perforations | 1 (0.4) | 0 | 0 | 0 |
| Hepatic events | 0 | 0 | 0 | 0 |
| Deaths, n (%) | 2 (0.7) | 4 (1.4) | 2 (0.7) | 1 (0.3) |
| Clinical laboratory abnormalities | ||||
| Neutropenia | ||||
| Grade −3 (<1.0–0.5×109/L) | 1 (0.4) | 2 (0.7) | 10 (3.4) | 8 (2.7) |
| Grade −4 (<0.5×109/L) | 0 | 0 | 0 | 1 (0.3) |
| Thrombocytopenia (based on platelet count) | ||||
| Grade −3 (<50–25×109/L) | 1 (0.4) | 1 (0.3) | 0 | 0 |
| Grade −4 (<25×109/L) | 1 (0.4) | 0 | 1 (0.3) | 0 |
| ALT elevations | ||||
| Grade 1 (>ULN–2.5× ULN) | 120 (42.6) | 125 (43.3) | 136 (46.9) | 115 (39.4) |
| Grade 2 (>2.5–5× ULN) | 21 (7.4) | 35 (12.1) | 59 (20.3) | 19 (6.5) |
| Grade 3 (>5.0–20× ULN) | 3 (1.1) | 10 (3.5) | 10 (3.4) | 5 (1.7) |
| Grade 4 (>20× ULN) | 0 | 0 | 0 | 0 |
| AST elevations | ||||
| Grade 1 (>ULN–2.5× ULN) | 88 (31.2) | 95 (32.9) | 137 (47.2) | 86 (29.5) |
| Grade 2 (>2.5–5× ULN) | 11 (3.9) | 12 (4.2) | 18 (6.2) | 9 (3.1) |
| Grade 3 (>5.0–20× ULN) | 1 (0.4) | 1 (0.3) | 5 (1.7) | 3 (1.0) |
| Grade 4 (>20× ULN) | 0 | 0 | 0 | 0 |
All values are n (%).
ALT ULN=55 U/L.
AST ULN=40 U/L.
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; MTX, methotrexate; SAE, serious adverse event; TCZ, tocilizumab; ULN, upper limit of normal.