Efficacy and safety of JAK inhibitors compared to standard care/placebo

The information presented in the summary of findings table below comes from a living network meta-analysis that combines all the available evidence on drug therapies for COVID-19. This statistical approach allows us to obtain estimates of effect for all potential comparisons, even those that have not been compared head-to-head in trials. We present the most trustworthy estimates of effect, based on the GRADE approach.

Comparison of JAK inhibitors to standard care/placebo:

Summary of Findings Table

Population: Patients with COVID-19 at any severity

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OutcomeN studies / participants with direct evidenceRelative effect estimatesAbsolute effect estimatesCertainty of the EvidencePlain language summarySource of highest certainty estimate
Mortality (closest to 90 days)6 RCTs;
3420 patients		Odds Ratio: 0.63
(95% CI 0.47 - 0.83)		Difference: 1 more per 1000
(95% CI 0 fewer to 1 more)		HIGHJAK inhibitors reduces mortality compared to standard care/placeboNMA
Mechanical ventilation (closest to 90 days)5 RCTs;
3195 patients		Odds Ratio: 0.78
(95% CI 0.56 - 1.04)		Difference: 1 more per 1000
(95% CI 1 more to 1 more)		MODERATEDue to serious imprecision,JAK inhibitors probably reduces mechanical ventilation compared to standard care/placeboNMA
AE leading to discontinuation (within 28 days)4 RCTs;
2309 patients		N/AN/AHIGHJAK inhibitors has little or no impact on adverse events compared to standard care/placeboNMA
Viral clearance closest to 7 days (± 3 days)
No data were reported for this outcome.
Duration of mechanical ventilation (in days)2 RCTs;
328 patients		N/ADifference: 3 fewer days
(95% CI 6 fewer to 1 fewer)		HIGHJAK inhibitors reduces duration of mechanical ventilation compared to standard care/placeboNMA
Length of hospital stay (in days)6 RCTs;
3413 patients		N/ADifference: 1 fewer days
(95% CI 2 fewer to 0 fewer)		HIGHJAK inhibitors has little or no impact on duration of hospitalization compared to standard care/placeboDIRECT
Time to symptom resolution4 RCTs;
3030 patients		Ratio of Means: 0.93
(95% CI 0.75 - 1.15)		Difference: 1 more days
(95% CI 1 more to 1 more)		MODERATEDue to serious imprecisionJAK inhibitors probably has little or no impact on time to symptom resolution compared to standard care/placeboNMA
Time to viral clearance (in days)
No data were reported for this outcome.
Length of intensive care unit stay (in days)
No data were reported for this outcome.
Admission to hospital (within 28 days)
No data were reported for this outcome.
Mechanical ventilation-free days (within 28 days; in days)0 RCTs; 0 patientsN/ADifference: 1 more days
(95% CI 1 fewer to 2 more)		MODERATEDue to serious imprecisionJAKi probably has little or no impact on ventilation-free days compared to standard care/placeboNMA

Abbreviations: AE, adverse events; 95% CI, 95% credible interval; NMA, network meta-analysis; N/A, not applicable; RCT, randomized control trial

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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