Covid-19 living Data

Pharmacologic treatments for covid-19 patients

Casirivimab+Imdevimab (REGN-COV2) vs Standard care/Placebo

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

Outpatients

Forest plots
(last update: 2022-12-06)

Summary of findings
(last update: 2022-12-06)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Casirivimab+Imdevimab (REGN-COV2)
Comparison: Standard care/Placebo

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	Outcome not yet measured or reported
Clinical improvement D60	Outcome not yet measured or reported
Hospitalisation or death	RR: 0.28 (0.18 - 0.44)	26 fewer per 1000 (from 29 fewer to 20 fewer)		Low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding adequate randomization, missing data, and selection of the reported results Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to low number of participants/events
3 trials Weinreich D, 2021; Weinreich D(2). 2022; O'Brien M, 2022 5021 participants		Casirivimab+Imdevimab (REGN-COV2) 10 per 1,000 (6 - 16)	Standard care/Placebo 36 per 1,000	1 additional study was identified that assessed this outcome, but no results were reported.
WHO progression score (level 7 or above) D28	RR: ( - )	Zero events in both groups		Very low certainty Reasons to downgrade Risk of bias: Not serious 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 no events in both groups
1 trials Portal Celhay C, 2022 413 participants		Casirivimab+Imdevimab (REGN-COV2) 0 per 1,000 ( - )	Standard care/Placebo 0 per 1,000
WHO progression score (level 7 or above) D60	RR: ( - )	Zero events in both groups		Very low certainty Reasons to downgrade Risk of bias: Not serious 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 no events in both groups
1 trials Portal Celhay C, 2022 413 participants		Casirivimab+Imdevimab (REGN-COV2) 0 per 1,000 ( - )	Standard care/Placebo 0 per 1,000
All-cause mortality D28	RR: 0.51 (0.09 - 2.95)	1 fewer per 1000 (from 1 fewer to 3 more)		Low certainty Reasons to downgrade Risk of bias: Serious Risk of bias downgraded by 1 level: some concerns regarding adequate randomization, and missing data Inconsistency: Not serious Indirectness: Not serious Imprecision: Serious due to low number of participants/events
4 trials O'Brien M, 2022; Weinreich D, 2021; Weinreich D (2), 2021; Portal Celhay C, 2022 5434 participants		Casirivimab+Imdevimab (REGN-COV2) 1 per 1,000 (0 - 5)	Standard care/Placebo 2 per 1,000
All-cause mortality D60	RR: ( - )	Zero events in both groups		Very low certainty Reasons to downgrade Risk of bias: Not serious 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 no events in both groups
1 trials Portal Celhay C, 2022 413 participants		Casirivimab+Imdevimab (REGN-COV2) 0 per 1,000 ( - )	Standard care/Placebo 0 per 1,000
Viral negative conversion D7	Outcome not yet measured or reported
Adverse events	RR: 0.70 (0.53 - 0.93)	142 fewer per 1000 (from 223 fewer to 33 fewer)		Moderate certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious We presume that the adverse event rates and the corresponding relative risks, are similar across diverse settings, 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 O'Brien M, 2022 314 participants		Casirivimab+Imdevimab (REGN-COV2) 332 per 1,000 (252 - 441)	Standard care/Placebo 475 per 1,000
Serious adverse events	RR: 0.37 (0.09 - 1.52)	13 fewer per 1000 (from 19 fewer to 11 more)		Low certainty Reasons to downgrade Risk of bias: Not serious 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
3 trials O'Brien M, 2022; Weinreich DM, 2020; Portal Celhay C, 2022 1002 participants		Casirivimab+Imdevimab (REGN-COV2) 8 per 1,000 (2 - 32)	Standard care/Placebo 21 per 1,000

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

Hospitalized patients

Forest plots
(last update: 2022-10-20)

Summary of findings
(last update: 2022-10-23)

Patient or population: COVID-19 patients
Setting: Worldwide
Intervention: Casirivimab+Imdevimab (REGN-COV2)
Comparison: Standard care/Placebo

Outcome	Relative effect (95% CI)	Absolute effect (95% CI)¹		Certainty of the Evidence (GRADE)
Clinical improvement D28	RR: 1.03 (0.98 - 1.09)	21 more per 1000 (from 14 fewer to 63 more)		Low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Serious Inconsistency downgraded by 1 level: I²=: 60.1% Indirectness: Not serious Imprecision: Serious due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect/trivial effect
2 trials Somersan-Karakaya S, 2022; Horby P, 2021 11149 participants		Casirivimab+Imdevimab (REGN-COV2) 716 per 1,000 (681 - 757)	Standard care/Placebo 695 per 1,000
Clinical improvement D60	RR: 1.06 (0.99 - 1.13)	44 more per 1000 (from 7 fewer to 96 more)		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 Somersan-Karakaya S, 2022 1364 participants		Casirivimab+Imdevimab (REGN-COV2) 781 per 1,000 (729 - 833)	Standard care/Placebo 737 per 1,000
WHO progression score (level 7 or above) D28	RR: 0.70 (0.51 - 0.96)	38 fewer per 1000 (from 63 fewer to 5 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 Somersan-Karakaya S, 2022 1364 participants		Casirivimab+Imdevimab (REGN-COV2) 90 per 1,000 (65 - 123)	Standard care/Placebo 128 per 1,000
WHO progression score (level 7 or above) D60	Outcome not yet measured or reported
All-cause mortality D28	RR: 0.82 (0.58 - 1.16)	36 fewer per 1000 (from 84 fewer to 32 more)		Very low certainty Reasons to downgrade Risk of bias: Not serious Inconsistency: Serious Inconsistency downgraded by 1 level: I²=:72.0% 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 Somersan-Karakaya S, 2022; Horby P, 2021 11149 participants		Casirivimab+Imdevimab (REGN-COV2) 163 per 1,000 (115 - 231)	Standard care/Placebo 199 per 1,000
All-cause mortality D60	RR: 0.73 (0.52 - 1.04)	29 fewer per 1000 (from 51 fewer to 4 more)		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 Somersan-Karakaya S, 2022 1364 participants		Casirivimab+Imdevimab (REGN-COV2) 78 per 1,000 (55 - 110)	Standard care/Placebo 106 per 1,000
Viral negative conversion D7	Outcome not yet measured or reported
Adverse events	Outcome not yet measured or reported
Serious adverse events	Outcome not yet measured or 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

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Permanent URL for this comparison: https://covid-nma.com/living_data/index.php?comparison=192

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Trial	Funding	Comparisons		Design	Participants	Sample size	Overall risk of bias Highest assessment	Full description
		Treatment 1	Treatment 2
NCT04666441 Portal Celhay C, JAMA Netw Open, 2022 Full text Full text Commentary Commentary Commentary	Private	Casirivimab+Imdevimab (REGN-COV2) 1200mg Casirivimab+Imdevimab (REGN-COV2) 1200mg	Placebo Casirivimab+Imdevimab (REGN-COV2) 1200mg	RCT	Outpatients with confirmed COVID-19 (asymptomatic-mild) treated by 47 centers in the USA	N=413	Low Details	Full description
NCT04426695 Somersan-Karakaya S, J Infect Dis, 2022 Full text Full text Full text Full text Commentary	Mixed	Casirivimab+Imdevimab (REGN-COV2) 8000mg	Placebo	RCT	Patients with confirmed COVID-19 (mild-moderate) admitted to 103 centers in USA, Brazil, Chile, Mexico, Moldova, and Romania	N=1364	Some concerns Details	Full description
NCT04452318 O'Brien M, JAMA, 2022 Full text Full text Full text Commentary Commentary Commentary	Mixed	Casirivimab+Imdevimab (REGN-COV2)	Placebo	RCT	Outpatients with confirmed COVID-19 (asymptomatic) treated at 112 centers in the Moldova, Romania, and USA.	N=314	Some concerns Details	Full description
NCT04381936, EudraCT 2020-001113-21, ISRCTN5018967 RECOVERY-REGEN Horby P, Lancet, 2022 Full text Full text Commentary Commentary Commentary	Mixed	Casirivimab+Imdevimab (REGN-COV2)	Standard care	RCT	Patients with suspected or confirmed COVID-19 (mild-critical) admitted to 127 centers in the UK	N=9785	Some concerns Details	Full description
NCT04425629 Weinreich D, N Engl J Med, 2021 Full text Full text Commentary Commentary Commentary	Mixed	Casirivimab+Imdevimab (REGN-COV2) 2400mg	Placebo	RCT	Outpatients with confirmed COVID-19 (mild) treated in 82 centers in Mexico and the USA.	N=3029	Some concerns Details	Full description
NCT04425629 Weinreich D (2), N Engl J Med, 2021 Full text Full text Full text Commentary Commentary Commentary	Mixed	Casirivimab+Imdevimab (REGN-COV2) 1200mg	Placebo	RCT	Outpatients with confirmed COVID-19 (mild) treated at 82 centers in Mexico and the USA.	N=1678	Some concerns Details	Full description
NCT04425629 Weinreich DM, N Engl J Med, 2020 Full text Commentary	Mixed	Casirivimab+Imdevimab (REGN-COV2)	Placebo	RCT	Outpatients with COVID-19 (symtomatic-mild) treated at 27 centers in USA	N=275	Low Details	Full description