Table.

Main characteristics of selected trials of tocilizumab and sarilumab in patients with COVID-19

	Design	Main intervention	Inclusion and exclusion criteria	Number of participants*	Time to enrolment	Primary outcome	Other outcomes	Main results	Comments†
CORIMUNO-19,20 published October, 2020 (NCT04331808)	Open-label RCT; 1:1 ratio	Tocilizumab 8 mg/kg versus usual care; option for second dose at 72 h	Adults with COVID-19-related moderate, severe, or critical pneumonia requiring O2 ≥3 L/min; patients on non-invasive or invasive mechanical ventilation excluded	131 (64 tocilizumab, 67 usual care)	Mean of 10 days from symptom onset; median of 1 day from hospitalisation	Score >5 on WHO 10-point Clinical Progression Scale at day 4; survival free from mechanical ventilation at day 14	Clinical status; overall survival; time to discharge; time to oxygen supply dependency	Indeterminate for primary outcome (median HR 0·58, 90% CrI 0·33–1·00); indeterminate for secondary outcomes	17% of patients on steroids; none on remdesivir; not critically ill
RCT-TCZ-COVID-19,21 published October, 2020 (NCT04346355)	Open-label RCT; 1:1 ratio	Tocilizumab 8 mg/kg versus standard of care; second dose at 12 h	Patients aged ≥18 years with COVID-19 pneumonia, PaO2/FiO2 200–300, and inflammatory phenotype, without mechanical ventilation at baseline; patients admitted to ICU, of advanced age, or with high burden of comorbidities excluded	126 (60 tocilizumab, 66 standard of care)	Median of 8 days from symptom onset; median of 2 days from hospitalisation	Clinical worsening at 14 days, including ICU admission, death, or PaO2/FiO2 <150	ICU admission; death at 14 and 30 days	Indeterminate for primary outcome (RR 1·05, 0·59–1·86); indeterminate for secondary outcomes	<5% of patients on steroids; none on remdesivir; not critically ill
BACC Bay,22 published December, 2020 (NCT04356937)	Double-blind RCT; 2:1 ratio	Tocilizumab 8 mg/kg versus placebo; single dose	Patients aged 19–85 years with confirmed COVID-19, hyperinflammatory state, and pulmonary infiltrates, fever, or need for supplemental O2; patients with higher risk of infection or O2 >10 L/min excluded	243 (161 tocilizumab, 82 placebo)	Median of 9 days from symptom onset; within 72 h of worsening	Mechanical ventilation or death	Clinical worsening (ordinal scale)	Indeterminate for primary outcome (HR 0·83, 0·38–1·81); indeterminate for secondary outcome	10% of patients on steroids; 32% on remdesivir; 4% on HFNO
TOCIBRAS,23 published January, 2021 (NCT04403685)	Open-label RCT; 1:1 ratio	Tocilizumab 8 mg/kg versus standard of care; single dose	Adults hospitalised with severe COVID-19 receiving supplemental O2 or mechanical ventilation, with high inflammatory markers; patients with uncontrolled infection, liver disease, or renal disease excluded	129 (65 tocilizumab, 64 standard of care)	Mean of 10 days from symptom onset	Clinical status (ordinal scale) at day 15	Death at 28 days	Indeterminate for primary outcome (OR 1·54, 0·66–3·66); indeterminate for secondary outcome	71% pf patients on steroids; none on remdesivir; 32% on non-invasive ventilation or HFNO; 16% on invasive mechanical ventilation
EMPACTA,24 published January, 2021 (NCT04372186)	Double-blind RCT; 2:1 ratio	Tocilizumab 8 mg/kg versus placebo; option for second dose at 8–24 h	Patients aged ≥18 years with COVID-19 pneumonia receiving supplemental O2; patients on non-invasive or invasive mechanical ventilation, with active infection, or at risk of imminent death excluded	388 (259 tocilizumab, 129 placebo)	Median of 8 days from symptoms; median of 1 day from diagnosis	Mechanical ventilation or death by day 28	Median time to hospital discharge; improvement in clinical status (ordinal scale)	Positive for primary outcome (HR 0·56, 0·33–0·97); indeterminate for secondary outcomes	>80% of patients on steroids; >70% on antivirals; 27% critically ill or on HFNO
COVACTA,25 published February, 2021 (NCT04320615)	Double-blind RCT; 2:1 ratio	Tocilizumab 8 mg/kg versus placebo; option for second dose at 8–24 h	Patients aged ≥18 years with COVID-19 pneumonia, and SpO2 ≤93% or PaO2/FiO2 <300; patients with active infection or at risk of imminent death excluded	452 (301 tocilizumab, 151 placebo)	Mean of 12 days from symptom onset; median of 5 days from mechanical ventilation	Clinical status (7-category ordinal scale) at day 28	Death at 28 days; ventilator-free days during 28 days	Indeterminate for primary outcome (between-group difference in median clinical status −1·00, −2·50 to 0·00); indeterminate for secondary outcomes	22% of patients on steroids (more in the placebo group); 25% on antivirals; 37% on invasive mechanical ventilation
REMAP-CAP,26 published February, 2021 (NCT02735707)	Open-label RCT (adaptive platform trial); balanced assignment (ratio dependent on number of interventions available at each site)	Tocilizumab 8 mg/kg or sarilumab 400 mg versus standard of care; option for second dose of tocilizumab at 12–24 h	Critically ill patients aged ≥18 years receiving respiratory or cardiovascular organ support, enrolled within 24 h of ICU admission; patients at risk of imminent death excluded	865 (353 tocilizumab, 48 sarilumab, 402 standard of care)	Median of 1 day from hospital admission to randomisation; median of 14 h from ICU admission	Organ support-free days or death up to 21 days	In hospital or death at 90 days; time to ICU discharge; time to hospital discharge	Positive for primary outcome (tocilizumab OR 1·64, 95% Crl 1·25–2·14; sarilumab 1.76, 1·17–2·91); positive for secondary outcomes	>80% of patients on steroids; 33% on remdesivir; 29% on HFNO; 42% on non-invasive ventilation; 29% on invasive mechanical ventilation
RECOVERY,27 preprint published February, 2021 (NCT04381936)	Open-label RCT (platform trial); 1:1 ratio	Tocilizumab 8 mg/kg versus usual care; option for second dose at 12–24 h	Patients aged ≥18 years with severe COVID-19, with SpO2 <92% on air or requiring O2 therapy, and C-reactive protein ≥75 mg/L; patients with active infection excluded	4116 (2022 tocilizumab, 2094 usual care)	Median of 10 days from symptom onset; median of 2 days from hospitalisation	All-cause death at 28 days	Time to hospital discharge; invasive mechanical ventilation or death at 28 days	Positive for primary outcome (RR 0·86, 0·77–0·96); positive for secondary outcomes	>80% of patients on steroids; 22% on remdesivir; 41% on non-invasive ventilation or HFNO; 14% on invasive mechanical ventilation
COVINTOC,28 published March, 2021 (CTRI/2020/05/025369)	Open-label RCT; 1:1 ratio	Tocilizumab 6 mg/kg versus standard of care; option for second dose at 12 h to 7 days	Patients aged ≥18 years admitted to hospital with moderate (respiratory rate 15–30 per min, SpO2 90–94%) to severe (respiratory rate ≥30 per min, SpO2 <90%, or ARDS or septic shock) COVID-19; patients with active infection or at risk of imminent death excluded	180 (90 tocilizumab, 90 standard of care)	Not reported	Progression of COVID-19 from moderate to severe or from severe to death up to day 14	Time to clinical improvement; proportion of patients with improvement in ASTCT CRS grade	Indeterminate for primary outcome (mean difference −3·7, −18·2 to 11·2); indeterminate for secondary outcomes	91% of patients on steroids; 42% on remdesivir; 27% on non-invasive ventilation; 5% on invasive mechanical ventilation
Lescure et al,29 published March, 2021 (NCT04327388)	Double-blind RCT (adaptive trial); 2:2:1 ratio	Sarilumab 400 mg or sarilumab 200 mg versus placebo; option for second dose at 24–48 h	Patients aged ≥18 years admitted to hospital with severe COVID-19 pneumonia or with critical disease requiring supplemental O2 or ICU admission; patients with active infection, dysfunction of ≥2 organ systems, on renal replacement therapy or extracorporeal support, or at risk of imminent death excluded	420 (173 sarilumab 400 mg, 161 sarilumab 200 mg, 86 placebo)	Median of 5 days from dyspnoea onset; median of 3 days from hospitalisation	Time to clinical improvement (2 or more points on 7-point ordinal scale)	Death at 28 days	Indeterminate for primary outcome sarilumab 400 mg HR 1·14, 0·84–1·54; sarilumab 200 mg 1·03, 0·75–1·40; indeterminate for secondary outcomes	20% of patients on steroids; <1% on remdesivir; 6% on HFNO; 2% on non-invasive ventilation; 12% on invasive mechanical ventilation

All measures of effect are shown alongside 95% CI (frequentist analysis) unless otherwise specified. ARDS=acute respiratory distress syndrome. ASTCT=American Society for Transplantation and Cellular Therapy. Crl=credible interval. CRS=cytokine release syndrome. HFNO=high-flow nasal oxygen. HR=hazard ratio. ICU=intensive care unit. OR=odds ratio. PaO₂/FiO₂=ratio of partial pressure of arterial oxygen to fraction of inspired oxygen. RR=risk ratio. SpO₂=oxygen saturation.

^*Total numbers might differ in the modified intention-to-treat analysis in individual trials.

^†Steroid and remdesivir use reflect pre-randomisation data where available, as a proportion of the entire sample enrolled (ie, all arms in the study).