Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

ACTT-2 Study Group Members

doi:10.1056/NEJMoa2031994

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

ACTT-2 Study Group Members

Uniformed Services University of the Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.

METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.

RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003).

CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

Original language	English
Pages (from-to)	795-807
Number of pages	13
Journal	New England Journal of Medicine
Volume	384
Issue number	9
DOIs	https://doi.org/10.1056/NEJMoa2031994
State	Published - 4 Mar 2021

Keywords

Adenosine Monophosphate/adverse effects
Adult
Aged
Alanine/adverse effects
Antiviral Agents/adverse effects
Azetidines/adverse effects
COVID-19/mortality
Double-Blind Method
Drug Therapy, Combination
Female
Hospital Mortality
Hospitalization
Humans
Janus Kinase Inhibitors/adverse effects
Male
Middle Aged
Oxygen Inhalation Therapy
Purines/adverse effects
Pyrazoles/adverse effects
Respiration, Artificial
Sulfonamides/adverse effects
Treatment Outcome
COVID-19 Drug Treatment

Access to Document

10.1056/NEJMoa2031994

Cite this

@article{58c4b94434084ca6a3a336bd58e66709,

title = "Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19",

abstract = "BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003).CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).",

keywords = "Adenosine Monophosphate/adverse effects, Adult, Aged, Alanine/adverse effects, Antiviral Agents/adverse effects, Azetidines/adverse effects, COVID-19/mortality, Double-Blind Method, Drug Therapy, Combination, Female, Hospital Mortality, Hospitalization, Humans, Janus Kinase Inhibitors/adverse effects, Male, Middle Aged, Oxygen Inhalation Therapy, Purines/adverse effects, Pyrazoles/adverse effects, Respiration, Artificial, Sulfonamides/adverse effects, Treatment Outcome, COVID-19 Drug Treatment",

author = "{ACTT-2 Study Group Members} and Kalil, {Andre C} and Patterson, {Thomas F} and Mehta, {Aneesh K} and Tomashek, {Kay M} and Wolfe, {Cameron R} and Varduhi Ghazaryan and Marconi, {Vincent C} and Ruiz-Palacios, {Guillermo M} and Lanny Hsieh and Susan Kline and Victor Tapson and Iovine, {Nicole M} and Jain, {Mamta K} and Sweeney, {Daniel A} and {El Sahly}, {Hana M} and Branche, {Angela R} and {Regalado Pineda}, Justino and Lye, {David C} and Uriel Sandkovsky and Luetkemeyer, {Anne F} and Cohen, {Stuart H} and Finberg, {Robert W} and Jackson, {Patrick E H} and Babafemi Taiwo and Paules, {Catharine I} and Henry Arguinchona and Nathaniel Erdmann and Neera Ahuja and Maria Frank and Myoung-Don Oh and Eu-Suk Kim and Tan, {Seow Y} and Mularski, {Richard A} and Henrik Nielsen and Ponce, {Philip O} and Taylor, {Barbara S} and LuAnn Larson and Rouphael, {Nadine G} and Youssef Saklawi and Cantos, {Valeria D} and Ko, {Emily R} and Engemann, {John J} and Amin, {Alpesh N} and Miki Watanabe and Joanne Billings and Marie-Carmelle Elie and Davey, {Richard T} and Burgess, {Timothy H} and Jennifer Ferreira and Michelle Green",

note = "Copyright {\textcopyright} 2020 Massachusetts Medical Society.",

year = "2021",

month = mar,

day = "4",

doi = "10.1056/NEJMoa2031994",

language = "English",

volume = "384",

pages = "795--807",

journal = "New England Journal of Medicine",

issn = "0028-4793",

number = "9",

}

TY - JOUR

T1 - Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

AU - ACTT-2 Study Group Members

AU - Kalil, Andre C

AU - Patterson, Thomas F

AU - Mehta, Aneesh K

AU - Tomashek, Kay M

AU - Wolfe, Cameron R

AU - Ghazaryan, Varduhi

AU - Marconi, Vincent C

AU - Ruiz-Palacios, Guillermo M

AU - Hsieh, Lanny

AU - Kline, Susan

AU - Tapson, Victor

AU - Iovine, Nicole M

AU - Jain, Mamta K

AU - Sweeney, Daniel A

AU - El Sahly, Hana M

AU - Branche, Angela R

AU - Regalado Pineda, Justino

AU - Lye, David C

AU - Sandkovsky, Uriel

AU - Luetkemeyer, Anne F

AU - Cohen, Stuart H

AU - Finberg, Robert W

AU - Jackson, Patrick E H

AU - Taiwo, Babafemi

AU - Paules, Catharine I

AU - Arguinchona, Henry

AU - Erdmann, Nathaniel

AU - Ahuja, Neera

AU - Frank, Maria

AU - Oh, Myoung-Don

AU - Kim, Eu-Suk

AU - Tan, Seow Y

AU - Mularski, Richard A

AU - Nielsen, Henrik

AU - Ponce, Philip O

AU - Taylor, Barbara S

AU - Larson, LuAnn

AU - Rouphael, Nadine G

AU - Saklawi, Youssef

AU - Cantos, Valeria D

AU - Ko, Emily R

AU - Engemann, John J

AU - Amin, Alpesh N

AU - Watanabe, Miki

AU - Billings, Joanne

AU - Elie, Marie-Carmelle

AU - Davey, Richard T

AU - Burgess, Timothy H

AU - Ferreira, Jennifer

AU - Green, Michelle

PY - 2021/3/4

Y1 - 2021/3/4

N2 - BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003).CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

AB - BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003).CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

KW - Adenosine Monophosphate/adverse effects

KW - Adult

KW - Aged

KW - Alanine/adverse effects

KW - Antiviral Agents/adverse effects

KW - Azetidines/adverse effects

KW - COVID-19/mortality

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Hospital Mortality

KW - Hospitalization

KW - Humans

KW - Janus Kinase Inhibitors/adverse effects

KW - Male

KW - Middle Aged

KW - Oxygen Inhalation Therapy

KW - Purines/adverse effects

KW - Pyrazoles/adverse effects

KW - Respiration, Artificial

KW - Sulfonamides/adverse effects

KW - Treatment Outcome

KW - COVID-19 Drug Treatment

U2 - 10.1056/NEJMoa2031994

DO - 10.1056/NEJMoa2031994

M3 - Article

C2 - 33306283

SN - 0028-4793

VL - 384

SP - 795

EP - 807

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 9

ER -

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

Abstract

Keywords

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