Covid-19 living Data

Pharmacologic treatments for covid-19 patients

Tocilizumab vs Standard care/Placebo

This comparison will not be updated. Last search date 14 Dec, 2022.

On March 18th, 2021, we published results of the living systematic review on IL-6 blocking agents which included all preprints and published trials published online up to February 11th, 2021.

Studies included but not extracted/included in the analysis: Ullah S, Medicina (Kaunas), 2022

We updated the the evidence on the effectiveness and safety of IL-6 blocking agents compared to standard care alone or to a placebo for people with COVID-19. On June 1, 2023, an update of the systematic review on IL-6 blocking agents was published. It included all preprints and published trials published online up to June 7, 2022.

Hospitalized patients

Forest plots
(last update: 2022-11-17)

Funnel plots
(last update: 2022-07-01)

Summary of findings
(last update: 2022-11-22)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Tocilizumab
Comparison: Standard care/Placebo

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 1.05 (1.00 - 1.11)	27 more per 1000 (from 0 fewer to 60 more)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns or high risk regarding adequate randomization, deviations from intended interventions, missing data, outcome measurement and selection of reported results, not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect/trivial effect
15 trials Salama C 2020; Stone JH 2020; IMMCOVA 2021; Broman N 2022; COVIDOSE-2 2021; Talaschian M 2021; Hermine O 2020; Rosas IO 2022; Declercq J 2021; Horby P 2021; Veiga VC 2021; Salvarani C 2020; HMO-0224-20 2021; Hermine O 2022; ARCHITECTS 2021 6116 participants		Tocilizumab 573 per 1,000 (545 - 605)	Standard care/Placebo 545 per 1,000
Clinical improvement D60	RR: 1.10 (0.81 - 1.48)	61 more per 1000 (from 116 fewer to 292 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding missing data, outcome measurement and selection of the reported results Inconsistency: Not serious Indirectness: Serious despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
1 trials Hermine O, 2022 97 participants		Tocilizumab 670 per 1,000 (493 - 901)	Standard care/Placebo 609 per 1,000
WHO progression score (level 7 or above) D28	RR: 0.90 (0.72 - 1.12)	22 fewer per 1000 (from 61 fewer to 26 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns or high risk regarding adequate randomization, deviations from intended interventions, and selection of reported results, not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
13 trials COVITOZ-01 2021; Salama C 2020; Stone JH 2020; IMMCOVA 2021; Broman N 2022; COVIDOSE-2 2021; Hermine O 2020; Rosas IO 2022; Declercq J 2021; Rutgers A 2021; Veiga VC 2021; HMO-0224-20 2021; ARCHITECTS 2021 2117 participants		Tocilizumab 196 per 1,000 (157 - 244)	Standard care/Placebo 217 per 1,000
WHO progression score (level 7 or above) D60	Outcome not yet measured or reported
All-cause mortality D28	RR: 0.88 (0.81 - 0.94)	34 fewer per 1000 (from 54 fewer to 17 fewer)		High certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns or high risk regarding adequate randomization, deviations from intended interventions, missing data, outcome measurement and selection of reported results, not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Not serious
18 trials Salama C 2020; Stone JH 2020; IMMCOVA 2021; Broman N 2022; COVIDOSE-2 2021; Talaschian M 2021; Hermine O 2020; Rosas IO 2022; Declercq J 2021; Rutgers A 2021; Soin AS 2021; Horby P 2021; Veiga VC 2021; Salvarani C 2020; HMO-0224-20 2021; Hermine O 2022; Gordon AC 2021; ARCHITECTS 2021 7454 participants		Tocilizumab 249 per 1,000 (229 - 266)	Standard care/Placebo 283 per 1,000
All-cause mortality D60	RR: 0.91 (0.80 - 1.04)	24 fewer per 1000 (from 53 fewer to 11 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns or high risk regarding adequate randomization, deviations from intended interventions, and missing data, not downgraded for risk of bias because the studies with these concerns contributed only a small proportion of weight to the effect estimate Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
9 trials Salama C 2020; Broman N 2022; Hermine O 2020; Rosas IO 2022; Declercq J 2021; HMO-0224-20 2021; Hermine O 2022; Derde L 2021; ARCHITECTS 2021 2792 participants		Tocilizumab 240 per 1,000 (211 - 274)	Standard care/Placebo 264 per 1,000
Viral negative conversion D7	Outcome not yet measured or reported
Adverse events	RR: 1.03 (0.95 - 1.12)	13 more per 1000 (from 22 fewer to 53 more)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns regarding adequate randomization, deviation from intended interventions, missing data, outcome measurement and selection of the reported results not downgraded for risk of bias Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for no effect/trivial effect and the possibility for harm
9 trials Salama C 2020; Stone JH 2020; Hermine O 2020; Wang D 2021; Rosas IO 2022; Soin AS 2021; Veiga VC 2021; Salvarani C 2020; Hermine O 2022 1811 participants		Tocilizumab 456 per 1,000 (421 - 496)	Standard care/Placebo 443 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
Serious adverse events	RR: 0.93 (0.81 - 1.07)	12 fewer per 1000 (from 32 fewer to 12 more)		Very low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding randomization, deviations from intended interventions, missing data, outcome measurement and selection of reported result Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
16 trials COVITOZ-01 2021; Salama C 2020; Stone JH 2020; IMMCOVA 2021; Broman N 2022; COVIDOSE-2 2021; Talaschian M 2021; Hermine O 2020; Wang D 2021; Rosas IO 2022; Declercq J 2021; Soin AS 2021; Veiga VC 2021; Salvarani C 2020; Hermine O 2022; Gordon AC 2021 3004 participants		Tocilizumab 155 per 1,000 (135 - 178)	Standard care/Placebo 167 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.

¹The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

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click here for Hospitalized patients

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Permanent URL for this comparison: https://covid-nma.com/living_data/index.php?comparison=28

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Trial	Funding	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Treatment 1	Treatment 2
NCT04330638; EudraCT2020-001500-41 COV-AID Declercq J, Lancet Respir Med, 2021 Full text Commentary Commentary	Public/non profit	Anakinra Tocilizumab Siltuximab Anakinra Anakinra Tocilizumab Anakinra + Tocilizumab	Standard care Standard care Standard care Tocilizumab Siltuximab Siltuximab Standard care	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to 16 centers in Belgium.	N=342	Some concerns Details	Full description
NCT04577534 COVIDSTORM Broman N, Clin Microbiol Infect, 2022 Full text Commentary	No specific funding	Tocilizumab	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to a single center in Finland.	N=88	Some concerns Details	Full description
NCT04377750 HMO-0224-20 HMO-0224-20, Unpublished, 2021 Extracted from REACT meta-analysis: Full text	Public/non profit	Tocilizumab	Placebo	RCT	Patients with confirmed COVID-19 (severe-critical) admitted to multiple centers in Israel.	N=54	High Details	Full description
NCT04412291, EudraCT 2020-001748-24 IMMCOVA IMMCOVA, Unpublished, 2021 Extracted from REACT meta-analysis: Full text	Public/non profit	Tocilizumab	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to a multiple centerd in Sweden	N=49	Low Details	Full description
NCT04435717 COVITOZ-01 COVITOZ-01, Unpublished, 2021 Extracted from REACT meta-analysis: Full text	Public/non profit	Tocilizumab	Standard care	RCT	Patients with suspected or confirmed COVID-19 (mild-moderate-severe) admitted to a single center in Spain.	N=26	Low Details	Full description
NCT04479358 COVIDOSE-2 COVIDOSE-2, Unpublished, 2021 Extracted from REACT meta-analysis: Full text	Public/non profit	Tocilizumab	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to multiple centers in the USA	N=28	Low Details	Full description
NCT04331808 CORIMUNO-TOCI-2 Hermine O, Eur Respir J, 2022 Full text Commentary	Public/non profit	Tocilizumab	Standard care	RCT	Patients with suspected or confirmed COVID-19 (severe-critical) admitted to 12 centers in France.	N=97	Some concerns Details	Full description
NCT04412772 ARCHITECTS ARCHITECTS, Unpublished, 2021 Extracted from REACT meta-analysis: Full text	Public/non profit	Tocilizumab	Placebo	RCT	Patients with confirmed COVID-19 (critical) admitted to a single center in the USA.	N=21	Low Details	Full description
NCT02735707 REMAP-CAP Derde L, medRxiv, 2021 Full text Commentary Commentary	Mixed	Tocilizumab Sarilumab Anakinra	Standard care	RCT	Patients with suspected or confirmed COVID-19 (moderate to critical) admitted to 133 centers in 9 countries	N=2253	Some concerns Details	Full description
IRCT20081027001411N4 Talaschian M, Research Square, 2021 Full text Commentary Commentary	Public/non profit	Tocilizumab	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to a single center in Iran	N=40	High Details	Full description
Trial NL8504 Rutgers A, PLoS ONE, 2022 Full text Full text Commentary Commentary	Mixed	Tocilizumab	Standard care	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to 11 centers in the Netherlands.	N=354	Low Details	Full description
CTRI/2020/05/025369 COVINTOC Soin AS, Lancet Respir Med, 2021 Full text Commentary	Mixed	Tocilizumab	Standard care	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to 12 centers in India	N=180	Some concerns Details	Full description
NCT04381936, ISRCTN50189673 RECOVERY (TCZ) Horby P, Lancet, 2021 a Full text Commentary Commentary	Public/non profit	Tocilizumab	Standard care	RCT	Patients with suspected or confirmed COVID-19 (moderate-critical) admitted to 131 centers in the UK	N=4116	Some concerns Details	Full description
NCT04403685 TOCIBRAS Veiga VC, BMJ, 2021 Full text Commentary Commentary	Mixed	Tocilizumab	Standard care	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to 9 centers in Brazil	N=129	Some concerns Details	Full description
NCT02735707 REMAP-CAP Gordon AC, N Engl J Med, 2021 Full text Full text Commentary Commentary	Mixed	Tocilizumab Sarilumab	Standard care	RCT	Patients with confirmed or suspected COVID-19 (severe-critical) admitted to 113 centers in Australia, Ireland, the Netherlands, New Zealand, Saudi Arabia, UK.	N=826	Some concerns Details	Full description
NCT04372186 EMPACTA Salama C, N Engl J Med, 2020 Full text Full text Commentary Commentary	Private	Tocilizumab	Placebo	RCT	Patients with confirmed COVID-19 (mild-severe) admitted to 65 centers in Brazil, Kenya, Mexico, Peru, South Africa, and USA	N=388	Some concerns Details	Full description
NCT04356937 Stone JH, N Engl J Med, 2020 Full text Commentary	Private	Tocilizumab	Placebo	RCT	Patients with COVID-19 (mild-severe) admitted to seven centers in USA	N=243	Low Details	Full description
NCT04346355 Salvarani C, JAMA , 2020 Full text Commentary	Mixed	Tocilizumab	Standard care	RCT	Patients with confirmed COVID-19 (severe) admitted to 24 centers in Italy	N=126	Some concerns Details	Full description
NCT04331808 CORIMUNO-TOCI 1 Hermine O, JAMA Intern Med, 2020 Full text Commentary	Public/non profit	Tocilizumab	Standard care	RCT	Patients with COVID-19 (moderate-severe) admitted to nine centers in France	N=131	Some concerns Details	Full description
ChiCTR2000029765 Wang D, Front Med, 2021 Full text Full text Commentary	Public/non profit	Tocilizumab	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to 6 centers in China	N=65	Some concerns Details	Full description
NCT04320615 COVACTA Rosas IO, EClinicalMedicine, 2022 Full text Full text Commentary Commentary	Mixed	Tocilizumab	Placebo	RCT	Patients with confirmed COVID-19 (mild-critical) admitted to multiple centers across 9 countries	N=452	Some concerns Details	Full description