Table 5.
Major adverse events associated with tocilizumab during clinical trials
| Article | Adverse events | ||
|---|---|---|---|
| First author or study group | Ref. | Placebo | Tocilizumab |
| REMAP-CAP | [98] |
Four bleeding events Seven thromboses |
One secondary bacterial infection Five bleeding events two cardiac events One deterioration in vision |
| Rosas IO | [54] |
Patients with at least 1 AE: 116 (81.1%) Infections: 58 (40.6%) Serious: 37 (25.9%) Opportunistic: 1 (0.7%) |
Patients with at least 1 AE: 228 (77.3%) Infections: 113 (38.3%) Serious: 62 (21.0%) Opportunistic: 1 (0.3%) |
| Veiga VC | [96] |
Any: 21 (34%) Secondary infection: 14.7 (8.2%) Thrombotic events: 4 (6%) Neutropenia: 0(0%) Severe raised in ALT, AST, or bilirubin level: 3(5%) |
Any: 29 (43%) Secondary infection: 11.3 (8.0%) Thrombotic events: 3 (5%) Neutropenia: 1 (1%) Severe raised in ALT, AST, or bilirubin level: 7(10%) |
| RECOVERY | [127] | - |
One pulmonary abscess One external otitis One Staphylococcus aureus bacteremia |
| Stone JH | [43] |
Infection of grade 3 or 4: 14 (17.1%) DVT: 3(3.7%) PE: 2 (2.4%) Stroke: 0 Neutropenia (≥ grade 3): 1 (1.2%) |
Infection of grade 3 or 4: 13 (8.1%) DVT: 2 (1.2%) PE: 2 (1.2%) Stroke: 2 (1.2%) Neutropenia (≥ grade 3): 22 (13.7%) |
| Gupta S | [99] |
Secondary infection: 1085 (31.1%) Thrombotic complications: 342 (9.8%) AST or ALT level elevation (> 250U/L): 452 (12.9%) |
Secondary infection: 140 (32.3%) Thrombotic complications: 46 (10.6%) AST or ALT level elevation (> 250U/L): 72 (16.6%) |
| Salvarani C | [42] |
Any: 7 (11.1%) Infection: 4 (6.3%) Laboratory abnormalities: 2 (3.2%) Vascular disorders: 0 |
Any: 14 (23.3%) Infection: 1 (1.7%) Laboratory abnormalities: 8 (13.3%) Vascular disorders: 1 (1.7%) |
| Hermine O | [100] |
At least one: 36 (54%) No. of events: 86 Patients with at least 1 SAE: 29 (43%) Hepatic cytolysis: 4 Neutropenia: 0 ARDS (death): 19 (9%) Bacterial sepsis: 11 Fungal sepsis: 2 PE (death): 3 |
At least one: 28 (44%) No. of events: 66 Patients with at least 1 SAE: 20 (32%) Hepatic cytolysis: 4 Neutropenia: 4 ARDS (death): 9 (7%) Bacterial sepsis: 2 Fungal sepsis: 0 PE (death): 0 |
| Lescure FX | [52] |
Total: 55 (65%) Leading to death: 9 (11%) |
Sarilumab (200 mg): - Total: 103 (65%) - Leading to death: 17 (11%) Sarilumab (400 mg): - Total: 121 (70%) - Leading to death: 18 (10%) |
| Soin AS | [53] |
Total: 22 (25%) Serious: 15 (17%) ARDS: 7 |
Total: 33 (36%) Serious: 18 (20%) ARDS: 7 |
| Guaraldi G | [56] |
Secondary infection*: 14 (4%) Neutropenia: 0 |
Secondary infection*: 24 (13%) Neutropenia: 1 (<1%) |
| SARTRE | [58] |
Overall: 15.7% Infection and infestation: 2.9% Increased Alanine aminotransferase: 2.9% Increased aminotransferase: 2.0% Nervous system disorders: 1.0% Gastrointestinal disorders: 0.0% Blood and lymphatic system disorders: 0.0% |
Overall: 18.2% Infection and infestation: 1.0% Increased Alanine aminotransferase: 7.1% Increased aminotransferase: 5.1% Nervous system disorders: 0.0% Gastrointestinal disorders: 1.0% Blood and lymphatic system disorders: 2.0% |
| REMDACTA | [125] |
P+R: - Overall: 530 - Of “special interest”: 149 . Infection: 33.3% . Serious infection: 24.9% . Opportunistic: 2.3% . Bleeding: 10.3% . Serious bleeding: 3.3% . Stroke: 3.8% . Hepatic events: 1.4% .Gastrointestinal perforation: 0.5% |
T+R: - Overall: 1094 - Of “special interest”: 268 . Infection: 30.5% . Serious infection: 20.0% . Opportunistic: 0.7% . Bleeding: 12.8% . Serious bleeding: 2.6% . Stroke: 2.3% . Hepatic events: 1.4% .Gastrointestinal perforation: 0.2% |
| CORIMUNO-SARI-1 | [121] |
At least one AE :33 (43%) Multiple AE: 11 (14%) Serious AE: 28 (37%) ---ARDS:11 ---Bacteria sepsis:7 ---Hepatic cytolysis: 3 ---Neutropenia: 0 ---Death: 16 (21%) |
At least one AE: 37 (54%) Multiple AE: 17 (25%) Serious AE: 27 (40%) ---ARDS: 7 ---Bacteria sepsis: 12 ---Hepatic cytolysis: 6 ---Neutropenia: 5 Death:10 (15%) |
| SARICOR | [120] |
AE: 39 Cytolysis: 1 Nosocomial infection: 3 Bacteremia: 1 Tachyarrhythmia: 2 |
---S200: AE: 37 Cytolysis: 0 Nosocomial infection: 5 Bacteremia: 1 Tachyarrhythmia: 0 ---S400: AE: 39 Cytolysis: 1 Nosocomial infection: 2 Bacteremia: 1 Tachyarrhythmia: 1 |
| EMPACTA | [97] |
Total AE: 187 At least 1 AE: 67 (52.8%) Serious AE: 25 (19.7%) Death: 15 (11.8%) Infection: 16 (12.6%) Serious infection: 9 (7.1%) |
Total AE: 250 At least 1 AE: 127 (50.8%) Serious AE: 38 (15.2%) Death: 29 (11.6%) Infection: 25 (10.0%) Serious infection: 13 (5.2%) |
| Sivapalasingam S | [61] |
- Severe patients > TEAE: 7 (28.0%) > SAE: 1 (4.0%) > TEAE LD: 0 - Critical patients > TEAE: 28 (63.6) > SAE: 26 (59.1%) > TEAE LD: 14 (31.8%) - MSOD/IC patients > TEAE: 16 (76.2%) > SAE: 12 (57.1%) > TEAE LD: 9 (42.9%) MSOD/IC patients |
- Severe patients * S200: > TEAE: 19 (38.0%) > SAE: 5 (10.0%) > TEAE LD: 2 (4.0%) *S400: > TEAE: 25 (49.0%) > SAE: 16 (31.4%) > TEAE LD: 8 (15.7%) - Critical patients * S200: > TEAE: 69 (73.4%) > SAE: 56 (59.6%) > TEAE LD: 37 (39.4%) *S400: > TEAE: 56 (63.6%) > SAE: 41 (46.6%) > TEAE LD: 22 (25.0%) - MSOD/IC patients * S200: > TEAE: 35 (81.4%) > SAE: 29 (67.4%) > TEAE LD: 20 (46.5%) *S400: > TEAE: 33 (80.5%) > SAE: 27 (65.9%) > TEAE LD: 15 (36.6%) |
| CORIMUNO-19 bis | [122] |
Tocilizumab AE: 30 (70%) SAE: 27 (63%) ARDS: 15 Bacterial and fungal sepsis: 13 Hepatic cytotoxicity: 5 Neutropenia: 0 Sarilumab AE: 22 (68%) SAE: 19 (57.6%) ARDS: 9 Bacterial and fungal sepsis: 4 Hepatic cytotoxicity: 5 Neutropenia: 2 |
Tocilizumab AE: 33 (67%) SAE: 31 (63%) ARDS: 13 Bacterial and fungal sepsis: 27 Hepatic cytotoxicity: 12 Neutropenia:1 Sarilumab AE: 32 (68%) SAE: 31 (64.6%) ARDS: 15 Bacterial and fungal sepsis: 19 Hepatic cytotoxicity: 3 Neutropenia: 0 |
AE Adverse event, ARDS acute respiratory distress syndrome, DVT Deep venous thrombosis, MSOD/IC multi-system organ dysfunction/Immunocompromised, PE Pulmonary embolism, SAE severe adverse event, TEAE treatment-emergent adverse event, TEAE LD treatment-emergent adverse event leading to death
P+R: Placebo and Remdesivir
T+R: Tocilizumab and Remdesivir
*(p < 0.0001)