Tocilizumab reduces mortality and mechanical ventilation requirement in hospitalized patients with COVID-19 and hypoxemia. |
Mortality benefit is confirmed and amplified in the severe COVID-19 group but not in the non-severe COVID-19 group. |
Mechanical ventilation incidence benefit is confirmed in both groups (severe COVID-19 group and non-severe COVID-19 group). |
Tocilizumab is effective in COVID-19 pneumonia. The greatest benefit is observed in severe COVID-19 pneumonia. |
Digital Features
Introduction
Methods
Search Strategy and Selection Criteria
Study Selection and Data Extraction
Risk of Bias Assessment
Statistical Analysis
Results
Study Selection and Characteristics
Studies | Study design | Country | Number of patients | TCZ regimena |
---|---|---|---|---|
Salvarini et al. [5] (RCT-TCZ) | Open-label, controlled trial | Italy, 24 sites | 126 patients (60 in TCZ arm) | Two doses (second dose 12 h later) |
Stone et al. [6] (BACC-bay) | Double-blind, placebo-controlled trial | USA | 243 patients (161 in TCZ arm) | Single dose |
Salama et al. [7] (EMPACTA) | Double-blind, placebo-controlled trial | 6 countries in America and Africa | 389 patients (249 in TCZ arm) | Single dose. Possibility of a 2nd dose 8–24 h later |
Hermine et al. [8] (CORIMUNO-TOCI) | Open-label, controlled trial | France, 9 sites | 131 patients (63 in TCZ arm) | Single dose. Possibility of a 2nd dose 48 h later |
Veiga et al. [9] (TOCIBRAS) | Open-label, controlled trial | Brazil, 9 sites | 129 patients (65 in TCZ arm) | Single dose |
Soin et al. [11] (COVINTOC) | Open-label, controlled trial | India, 12 sites | 180 patients (90 in TCZ arm) | Single dose. Possibility of a 2nd dose 12–168 h later |
Rosas et al. [10] (COVACTA) | Double-blind, placebo-controlled trial | 9 countries in Europe and North America | 444 patients (294 in TCZ arm) | Single dose |
Horby et al. [4] (RECOVERY) | Open-label, controlled trial | UK | 4116 patients (2022 in TCZ arm) | Single dose. Possibility of a 2nd dose 12–24 h later |
Gordon et al. [3] (REMAP-CAP) | Open-label, controlled trial | Europe, Oceania, and North America | 755 patients (353 in TCZ arm) | Single dose. Possibility of a 2nd dose 12–24 h later |
Salvarani et al. [5] | Stone et al. [6] | Salama et al. [7] | Veiga et al. [9] | Hermine et al. [8] | Soin et al. [11] | Rosas et al. [10] | Horby et al. [4] | Gordon et al. [3] | ||
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Respiratory support | ||||||||||
Respiratory support at baseline in TCZ arm | Not detailed but 72% of patients (43/60) had a PaO2/FiO2 ≥ 250 mmHg (so a O2 flow ≤ 3 L/min) | Ordinal scale scorea 2: 14% (23/161) 3: 83% (133/161) 4: 3% (5/161) | Ordinal scale scorec 2: 9% (24/249) 3: 65% (161/249) 4: 26% (64/249) | Ordinal scale scoreb 4: 60% (39/65) 5: 23% (15/65) 6: 17% (11/65) | WHO-CPS-Score (0–10)e: 5: 100% (63/63) | Respiratory support: supplemental O2: 89% (81/91) NIV: 31% (28/91) IMV: 5% (5/91) | Ordinal scale scored 2: 3% (9/294) 3: 27% (78/294) 4: 32% (94/294) 5: 15% (45/294) 6: 23% (68/294) | Respiratory support: low flow O2f: 46% (935/2022) NIV or HFNC: 41% (819/2022) IMV: 13% (268/2022) | Respiratory support:g HFNC: 29% (101/353) NIV: 42% (147/353) IMV: 29% (104/353) | |
Classification | O2 ≤ 3 L/min or no O2 | 72% | 97% | 9% | 0% | 60% | 64% | 3% | 46% | 0.3% |
3 L/min < O2 ≤ 6 L/min | 28% | 65% | 100% | 27% | ||||||
O2 > 6 L/min | 0% | 3% | ||||||||
HFNC or NIV | 0% | 0% | 26% | 0% | 23% | 31% | 32% | 41% | 70% | |
IMV (IMV < 24 h) | 0% | 0% | 0% | 0% | 17% (17%) | 5% | 38% | 13% | 29% (29%) | |
CRP level at baseline | ||||||||||
CRP in TCZ arm, median (IQR) or *mean (SD) | 105 (50–146) | 116 (67–191) | 125 | *160 (104) | 120 (75–220) | *111 (107) | *168 (101) | 143 (107–203) | 150 (85–221) | |
Significant resultsh | ||||||||||
Mortality at day 28 | No | No | No | No | No | No (in favor of TCZ in severe COVID-19) | No | In favor of TCZ | In favor of TCZ | |
MV or ICU incidence | No | No | In favor of TCZ | No | In favor of TCZ | No | No | In favor of TCZ | In favor of TCZ | |
Hospitalization characteristics | No | No | In favor of TCZ | In favor of TCZ | In favor of TCZ | No | In favor of TCZ | In favor of TCZ | In favor of TCZ | |
Safety | No | In favor of TCZ | No | No | In favor of TCZ | No | No | No | No | |
RCT risk of biasi | Some concerns | Low | Low | Some concerns | Some concerns | Some concerns | Low | Some concerns | Some concerns | |
Mortality rate in RCTs | ||||||||||
% of deaths in controlled arm (overall population) | 2% (2%) | 4% (5%) | 9% (10%) | 9% (15%) | 12% (12%) | 18% (15%) | 19% (20%) | 33% (31%) | 36% (32%) |