Adverse events (AE; safety population).
| All-control Population, n = 4199 | All-exposed Population (cutoff date: Feb. 17, 2010), n = 4009 | |||||||
|---|---|---|---|---|---|---|---|---|
| Control, n = 1555 | TCZ 4 mg/kg + DMARD/MTX, n = 774 | TCZ 8 mg/kg ± DMARD/MTX, n = 1870 | Overall | 0–12 Mo | 13–24 Mo | 25–36 Mo | > 36 Mo | |
| Total duration, PY | 824.6 | 564.6 | 1194.1 | 12293.1 | 3470.9 | 3026.1 | 2732.7 | 3063.5 |
| AE, rate/100 PY | ||||||||
| Anya | 339.0 | 358.0 | 381.6 | 257.2 | 379.4 | 275.8 | 252.4 | 224.5 |
| Severea,b | — | — | — | 16.8 | 22.2 | 16.7 | 15.8 | 12.9 |
| Led to withdrawala | 6.9 | 10.1 | 10.2 | 5.2 | 9.2 | 4.4 | 3.8 | 2.9 |
| Led to dose modification/interruptiona | 27.8 | 32.9 | 34.2 | 36.0 | 40.3 | 38.5 | 38.7 | 36.8 |
| Serious AE, rate/100 PY Anya | 14.4 | 13.6 | 14.5 | 14.1 | 15.5 | 13.4 | 14.8 | 13.6 |
| Death rate/100 PY | 0.73 | 0.00 | 0.75 | 0.45 | 0.55 | 0.33 | 0.44 | 0.29 |
| AE with rate ≥ 2/100 PY by SOCa | ||||||||
| Infections and infestations | 87.9 | 93.9 | 93.4 | 68.7 | 96.7 | 83.8 | 80.8 | 73.7 |
| Gastrointestinal disorders | 55.3 | 47.3 | 56.8 | 32.7 | 55.0 | 32.8 | 29.3 | 23.9 |
| Musculoskeletal and connective tissue disorders | 38.8 | 30.3 | 29.1 | 27.5 | 34.7 | 31.1 | 27.8 | 25.2 |
| Nervous system disorders | 20.5 | 21.4 | 24.0 | 12.8 | 22.4 | 13.0 | 10.6 | 8.9 |
| Skin and subcutaneous disorders | 19.6 | 29.4 | 31.7 | 15.6 | 27.3 | 14.5 | 12.0 | 10.8 |
| General disorders and administrative site conditions | 18.2 | 17.5 | 18.0 | 9.2 | 16.2 | 8.3 | 7.6 | 5.2 |
| Respiratory, thoracic, and mediastinal disorders | 14.8 | 18.4 | 17.5 | 11.8 | 17.1 | 12.3 | 11.0 | 10.1 |
| Injury, poisoning, and procedural complications | 13.9 | 15.8 | 15.8 | 14.5 | 16.9 | 15.1 | 14.3 | 13.7 |
| Investigations | 12.4 | 17.5 | 25.0 | 10.8 | 20.9 | 9.8 | 8.2 | 6.2 |
| Vascular disorders | 10.3 | 14.2 | 12.4 | 8.4 | 13.3 | 8.8 | 7.8 | 6.2 |
| Psychiatric disorders | 7.9 | 8.3 | 8.3 | 5.4 | 8.2 | 5.5 | 5.5 | 3.4 |
| Metabolism and nutrition disorders | 6.3 | 7.4 | 7.1 | 7.3 | 8.9 | 8.4 | 6.1 | 7.5 |
| Blood and lymphatic disorders | 5.3 | 5.7 | 7.3 | 5.2 | 7.4 | 4.6 | 5.4 | 5.5 |
| Eye disorders | 5.0 | 6.4 | 8.2 | 6.1 | 7.9 | 6.3 | 6.0 | 5.2 |
| Renal and urinary disorders | 4.0 | 2.7 | 4.1 | 2.9 | 3.6 | 2.8 | 2.7 | 2.8 |
| Reproductive and breast disorders | 4.4 | 4.3 | 5.3 | 3.4 | 4.6 | 3.4 | 2.9 | 3.0 |
| Cardiac disorders | 3.5 | 2.7 | 4.0 | 4.1 | 4.5 | 4.5 | 3.8 | 4.0 |
| Ear and labyrinth disorders | 3.3 | 3.9 | 2.9 | 2.3 | 3.1 | 2.7 | 2.2 | 1.6 |
| Neoplasms benign, malignant, unspecified (including cysts and polyps) | 1.7 | 5.1 | 2.6 | 3.1 | 3.5 | 2.9 | 3.4 | 3.0 |
| Immune disorders | 1.9 | 1.8 | 2.4 | 1.6 | 2.3 | 1.8 | 1.6 | 1.0 |
| Hepatobiliary disorders | 1.7 | 1.1 | 2.8 | 1.8 | 2.2 | 1.5 | 1.9 | 2.0 |
| SAE with rate ≥ 1/100 PY by SOCa | ||||||||
| Infections and infestations | 3.3 | 3.5 | 4.8 | 4.4 | 4.4 | 3.8 | 5.0 | 4.7 |
| Gastrointestinal disorders | 1.0 | 0.9 | 1.7 | 1.2 | 1.5 | 1.0 | 1.1 | 1.2 |
| Musculoskeletal and connective tissue disorders | 1.8 | 1.2 | 0.6 | 0.9 | 1.0 | 1.0 | 0.9 | 0.8 |
| Nervous system disorders | 0.7 | 1.4 | 0.8 | 0.8 | 1.0 | 0.8 | 0.7 | 0.7 |
| Injury, poisoning, and procedural complications | 1.1 | 1.1 | 1.8 | 1.2 | 1.4 | 1.5 | 1.0 | 1.0 |
| Cardiac disorders | 1.1 | 0.4 | 1.1 | 1.0 | 1.0 | 1.0 | 1.1 | 1.0 |
| Neoplasms, benign, malignant, unspecified (including cysts and polyps) | 0.8 | 1.8 | 0.5 | 1.2 | 1.0 | 1.0 | 1.4 | 1.3 |
↵a Multiple occurrences of the same AE in a patient are counted once in each period.
↵b Intensity of AE graded by the investigator as mild, moderate, or severe. PY: patient-years; SAE: serious adverse event; SOC: system organ class; TCZ: tocilizumab; DMARD: disease-modifying antirheumatic drug; MTX: methotrexate.