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editorial
. 2021 Jan 27:1–4. doi: 10.1080/14712598.2021.1880563

Table 1.

Review of RCTs analyzing the efficacy and safety of tocilizumab as immunomodulatory therapy for COVID-19

  COVACTA [15] ENVACTA [16] RCT-TCZ-COVID-19 [17] CORIMUNO-TOCI-1 [18] BACC Bay Tocilizumab Trial [19]
Type of RCT Blinded, placebo-controlled (2:1 ratio) Blinded, placebo-controlled (2:1 ratio) Open-label, no placebo-controlled (1:1 ratio) Open-label, no placebo-controlled (1:1 ratio) Blinded, placebo-controlled (2:1 ratio)
No. of sites (countries) 67 (Europe, US, Canada) 69 (Mexico, South America, Kenya, South Africa, US) 24 (Italy) 9 (France) 7 (US)
No. of participants 438 389 126 131 243
Age at enrrollment, years (mean ± SD or median [IQR]) 60.9 ± 14.6 [TCZ arm] 56.0 ± 14.3 60.0 (54.0–69.0) 64.0 (57.1–74.3) [TCZ arm] 59.8 (45.3–69.4)
Severe disease at enrrollmenta 301 (68.7%) 100 (26.5%) Not specified (patients on MV were excluded)b Not specified (patients on MV were excluded)c 11 (4.5%)
Days from symptom onset to randomization 11.0 (1.0–49.0) [TCZ arm] 8.0 (0.0–36.0) 8.0 (6.0–11.0) 10.0 (7.0–13.0) [TCZ arm] 9.0 (6.0–13.0)
Use of systemic corticosteroidsd 106 (36.1%) [TCZ arm], 79 (54.9%) [placebo arm] 200 (80.3%) [TCZ arm], 112 (87.5%) [placebo arm] None 21 (33%) [TCZ arm], 41 (61%) [SoC arm] 18 (11%) [TCZ arm], 5 (6%) [placebo arm]
Primary outcome Change in clinical status (on a 7-category ordinal scale) by day 28 Invasive MV, ECMO or death by day 28 Clinical worsening (MV, death and/or PaO2/FiO2 ratio <150) by day 14

  • MV or death by day 4

  • Survival with no MV by day 14

 Invasive MV or death (time-to-event analysis)
Main results Threshold for efficacy not met: OR 1.19 (95% CI: 0.81–1.76; P-value = 0.36) Threshold for efficacy met: HR 0.56 (95% CI: 0.32–0.97; P-value = 0.04) Threshold for efficacy not met: RR: 1.05 (95% CI: 0.59–1.86; P-value = 0.87)

  • MV or death by day 4: threshold for efficacy not met: ARD −9.0% (90% CI: −21.0% – 3.1%)

  • Survival with no MV by day 14: threshold for efficacy met: HR: 0.58 (90% CI: 0.33–1.00)

 Threshold for efficacy not met: HR: 0.83 (95% CI: 0.38–1.81; P-value = 0.64)
Selected secondary outcomes (TCZ vs. control arm) and safety signals No differences in 28-day mortality (19.7% vs. 19.4%) No differences in 28-day mortality (10.4% vs. 8.6%)
Numerically lower rate of serious infection with TCZ		 No differences in 14-day (1.7% vs. 1.6%) or 30-day mortality (3.3% vs. 1.6%) No differences in 14-day (11.1% vs. 8.9%) or 28-day mortality (11.1% vs. 11.9%)
Numerically lower rate of SAEs and serious bacterial infection with TCZ		 No differences in 14-day (4.4% vs. 1.3%) or 28-day mortality (5.6% vs. 3.8%)
Numerically lower rate of serious infection with TCZ

ARD: median absolute risk difference; CI: confidence interval; ECMO: extracorporeal membrane oxygenation; HR: hazard ratio; IQR: interquartile range; MV: mechanical ventilation; OR: odds ratio; RCT: randomized clinical trial; SAE: serious adverse event; PaO2/FiO2: partial pressure of arterial oxygen/fraction of inspired oxygen; SD: standard deviation; SoC: standard of care; TCZ: tocilizumab.

aPatients receiving high-flow oxygen or noninvasive or invasive mechanical ventilation. Definition of severity varied across trials.

bPatients were eligible for the RCT-TCZ-COVID-19 trial if they have a PaO2/FiO2 ratio between 200 and 300 mmHg. They were allowed to receive oxygen therapy with Venturi mask or high-flow nasal cannula but not invasive or noninvasive mechanical ventilation.

cPatients were eligible for the CORIMUNO-TOCI-1 trial if they had a WHO-CPS score of 5 with O2 levels of 3 L/min or higher but without noninvasive or invasive mechanical ventilation.

dSystemic corticosteroids as immunomodulatory therapy for COVID-19.