Covid-19 living Data

Pharmacologic treatments for covid-19 patients

Anakinra vs Standard care/Placebo

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

On Jan 26th, 2022, we published results of the Interleukin‐1 blocking agents for treating COVID‐19 which included all preprints and published trials published online up to November 5, 2021.

Hospitalized patients

Forest plots
(last update: 2022-10-07)

Summary of findings
(last update: 2022-10-13)

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

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 1.04 (0.94 - 1.16)	29 more per 1000 (from 44 fewer to 117 more)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns with adequate randomisation,deviation from intended intervention, outcome measurement, and selection of the 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
6 trials Mariette X, 2021; Kyriazopoulou E, 2021; Declerq J, 2021; Kharazmi AB, 2021; Elemekaty E, 2022; Audemard-Verger A, 2022 1018 participants		Anakinra 760 per 1,000 (687 - 847)	Standard care/Placebo 731 per 1,000
Clinical improvement D60	RR: 0.94 (0.79 - 1.11)	51 fewer per 1000 (from 178 fewer to 93 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns with deviation from intended intervetion, 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: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
2 trials Declerq J, 2021; Andersson H, 2022 126 participants		Anakinra 795 per 1,000 (668 - 939)	Standard care/Placebo 846 per 1,000
WHO progression score (level 7 or above) D28	RR: 0.76 (0.45 - 1.29)	44 fewer per 1000 (from 101 fewer to 53 more)		Very low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns with adequate randomization, deviation from intended intervention, and selection of the 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: Serious Inconsistency downgraded by 1 level: I²=:54.3% Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
4 trials Mariette X, 2021; Kyriazopoulou E, 2021; Kharazmi AB, 2021; Audemard-Verger A, 2022 823 participants		Anakinra 139 per 1,000 (83 - 237)	Standard care/Placebo 183 per 1,000
WHO progression score (level 7 or above) D60	RR: 0.54 (0.30 - 0.96)	47 fewer per 1000 (from 72 fewer to 4 fewer)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Multicentre study conducted across several countries, therefore not downgraded for indirectness Imprecision: Serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect/trivial effect
1 trials Kyriazopoulou E, 2021 606 participants		Anakinra 56 per 1,000 (31 - 99)	Standard care/Placebo 103 per 1,000
All-cause mortality D28	RR: 0.84 (0.47 - 1.49)	17 fewer per 1000 (from 58 fewer to 53 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns with adequate randomization, deviation from intended intervention, and selection of the 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
5 trials Mariette X, 2021; Kyriazopoulou E, 2021; Kharazmi AB, 2021; Elemekaty E, 2022; Audemard-Verger A, 2022 903 participants		Anakinra 91 per 1,000 (51 - 162)	Standard care/Placebo 109 per 1,000
All-cause mortality D60	RR: 1.05 (0.70 - 1.58)	13 more per 1000 (from 78 fewer to 151 more)		Very low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns regarding deviation from intended interventions and missing data not downgraded for risk of bias Inconsistency: Serious Inconsistency downgraded by 1 level: I²=:55.8% Indirectness: Not serious Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
5 trials Mariette X, 2021; Kyriazopoulou E, 2021; Declerq J, 2021; Andersson H, 2022; Derde L, 2021 1644 participants		Anakinra 273 per 1,000 (182 - 410)	Standard care/Placebo 260 per 1,000
Viral negative conversion D7	RR: 0.93 (0.63 - 1.37)	12 fewer per 1000 (from 61 fewer to 61 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Multicentre study conducted across several countries, therefore not downgraded for indirectness Imprecision: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
1 trials Kyriazopoulou E, 2021 606 participants		Anakinra 153 per 1,000 (104 - 226)	Standard care/Placebo 165 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
Adverse events	RR: 1.11 (0.92 - 1.35)	79 more per 1000 (from 57 fewer to 251 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns with adequate randomization, deviation from intended intervention, outcome measurement, and selection of the 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
5 trials Mariette X, 2021; Kyriazopoulou E, 2021; Kharazmi AB, 2021; Audemard-Verger A, 2022; Elmekaty E, 2022 903 participants		Anakinra 797 per 1,000 (660 - 969)	Standard care/Placebo 718 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
Serious adverse events	RR: 0.95 (0.71 - 1.28)	12 fewer per 1000 (from 69 fewer to 66 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Despite some concerns with adequate randomisation, deviation from intended intervention and 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: Very serious due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
6 trials Mariette X, 2021; Kyriazopoulou E, 2021; Kharazmi AB, 2021; Elemekaty E, 2022; Audemard-Verger A, 2022 914 participants		Anakinra 225 per 1,000 (168 - 303)	Standard care/Placebo 237 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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Permanent URL for this comparison: https://covid-nma.com/living_data/index.php?comparison=223

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Trial	Funding	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Treatment 1	Treatment 2
NCT04364009 ANACONDA Audemard-Verger A, Plos One, 2022 Full text Commentary Commentary	Public/non profit	Anakinra	Standard care	RCT	Patients with confirmed COVID-19 (moderate-severe) admitted to 20 centers in France.	N=71	Some concerns Details	Full description
NCT04643678 Elmekaty E, medRxiv, 2022 Full text Commentary Commentary	Public/non profit	Anakinra	Standard care	RCT	Patients with confirmed COVID-19 (moderate to critical) admitted to three centers in Qatar	N=80	Some concerns Details	Full description
NCT04324021 Andersson H, Unpublished, 2022 Full text	Private	Emapalumab Emapalumab Anakinra	Standard care Anakinra Standard care	RCT	Patients with suspected or confirmed COVID-19 (severe) admitted to 12 centers in USA and Italy.	N=16	Some concerns Details	Full description
IRCT20120703010178N20 Kharazmi AB, Immun Inflamm Dis, 2021 Full text Commentary	Private	Anakinra	Standard care	RCT	Patients with confirmed COVID-19 (moderate-critical) admitted to a single center in Iran.	N=30	Some concerns Details	Full description
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
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
NCT04680949; EudraCT 2020-005828-11 SAVE-MORE Kyriazopoulou E, Nat Med, 2021 Full text Full text Commentary Commentary	Mixed	Anakinra	Placebo	RCT	Patients with confirmed COVID-19 (mild-severe) admitted to 37 centers in Greece and Italy	N=606	Some concerns Details	Full description
NCT04341584 CORIMUNO-ANA-1 Mariette X, Lancet Respir Med, 2021 Full text Commentary	Public/non profit	Anakinra	Standard care	RCT	Patients with COVID-19 (moderate) admitted to 16 centers in France.	N=116	Some concerns Details	Full description