Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.
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
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
04 03 2021
04 03 2021
Historique:
pubmed:
12
12
2020
medline:
9
3
2021
entrez:
11
12
2020
Statut:
ppublish
Résumé
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. 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. 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). 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.).
Sections du résumé
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.).
Identifiants
pubmed: 33306283
doi: 10.1056/NEJMoa2031994
pmc: PMC7745180
doi:
Substances chimiques
Antiviral Agents
0
Azetidines
0
Janus Kinase Inhibitors
0
Purines
0
Pyrazoles
0
Sulfonamides
0
remdesivir
3QKI37EEHE
Adenosine Monophosphate
415SHH325A
baricitinib
ISP4442I3Y
Alanine
OF5P57N2ZX
Banques de données
ClinicalTrials.gov
['NCT04401579']
Types de publication
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
795-807Subventions
Organisme : NIAID NIH HHS
ID : K08 AI143923
Pays : United States
Organisme : BLRD VA
ID : I01 BX003714
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148685
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12023/22
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : UM1 AI148452
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148573
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148684
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002378
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002645
Pays : United States
Organisme : NIAID NIH HHS
ID : R38 AI140299
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148689
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148450
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148575
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148576
Pays : United States
Organisme : United States
ID : NCT04401579
Pays : United States
Investigateurs
Thomas F Patterson
(TF)
Philip O Ponce
(PO)
Barbara S Taylor
(BS)
Jan E Patterson
(JE)
Jason E Bowling
(JE)
Heta Javeri
(H)
Andre C Kalil
(AC)
LuAnn Larson
(L)
Angela Hewlett
(A)
Aneesh K Mehta
(AK)
Nadine G Rouphael
(NG)
Youssef Saklawi
(Y)
Nicholas Scanlon
(N)
Jessica J Traenkner
(JJ)
Ronald P Trible
(RP)
Emmanuel B Walter
(EB)
Noel Ivey
(N)
Thomas L Holland
(TL)
Guillermo M Ruiz-Palacios
(GM)
Alfredo Ponce de León
(A)
Sandra Rajme
(S)
Lanny Hsieh
(L)
Alpesh N Amin
(AN)
Miki Watanabe
(M)
Helen S Lee
(HS)
Susan Kline
(S)
Joanne Billings
(J)
Brooke Noren
(B)
Hyun Kim
(H)
Tyler D Bold
(TD)
Victor Tapson
(V)
Jonathan Grein
(J)
Fayyaz Sutterwala
(F)
Nicole Iovine
(N)
Lars K Beattie
(LK)
Rebecca Murray Wakeman
(R)
Matthew Shaw
(M)
Mamta K Jain
(MK)
Satish Mocherla
(S)
Jessica Meisner
(J)
Amneris Luque
(A)
Daniel A Sweeney
(DA)
Constance A Benson
(CA)
Farhana Ali
(F)
Robert L Atmar
(RL)
Hana M El Sahly
(HM)
Jennifer Whitaker
(J)
Ann R Falsey
(AR)
Angela R Branche
(AR)
Cheryl Rozario
(C)
Justino Regalado Pineda
(J)
José Arturo Martinez-Orozco
(JA)
David Chien Lye
(DC)
Sean W X Ong
(SWX)
Po Ying Chia
(PY)
Barnaby E Young
(BE)
Uriel Sandkovsky
(U)
Mezgebe Berhe
(M)
Clinton Haley
(C)
Emma Dishner
(E)
Valeria D Cantos
(VD)
Colleen F Kelley
(CF)
Paulina A Rebolledo Esteinou
(PA)
Sheetal Kandiah
(S)
Sarah B Doernberg
(SB)
Pierre-Cedric B Crouch
(PB)
Hannah Jang
(H)
Anne F Luetkemeyer
(AF)
Jay Dwyer
(J)
Stuart H Cohen
(SH)
George R Thompson
(GR)
Hien H Nguyen
(HH)
Robert W Finberg
(RW)
Jennifer P Wang
(JP)
Juan Perez-Velazquez
(J)
Mireya Wessolossky
(M)
Patrick E H Jackson
(PEH)
Taison D Bell
(TD)
Miranda J West
(MJ)
Babafemi Taiwo
(B)
Karen Krueger
(K)
Johnny Perez
(J)
Triniece Pearson
(T)
Catharine I Paules
(CI)
Kathleen G Julian
(KG)
Danish Ahmad
(D)
Alexander G Hajduczok
(AG)
Henry Arguinchona
(H)
Christa Arguinchona
(C)
Nathaniel Erdmann
(N)
Paul Goepfert
(P)
Neera Ahuja
(N)
Maria G Frank
(MG)
David Wyles
(D)
Heather Young
(H)
Myoung-Don Oh
(MD)
Wan Beom Park
(WB)
Chang Kyung Kang
(CK)
Vincent Marconi
(V)
Abeer Moanna
(A)
Sushma Cribbs
(S)
Telisha Harrison
(T)
Eu Suk Kim
(ES)
Jongtak Jung
(J)
Kyoung-Ho Song
(KH)
Hong Bin Kim
(HB)
Seow Yen Tan
(SY)
Humaira Shafi
(H)
Jaime M F Chien
(JMF)
Raymond K C Fong
(RKC)
Daniel D Murray
(DD)
Jens Lundgren
(J)
Henrik Nielsen
(H)
Tomas Jensen
(T)
Barry S Zingman
(BS)
Robert Grossberg
(R)
Paul F Riska
(PF)
Otto O Yang
(OO)
Jenny Ahn
(J)
Rubi Arias
(R)
Rekha R Rapaka
(RR)
Naomi Hauser
(N)
James D Campbell
(JD)
William R Short
(WR)
Pablo Tebas
(P)
Jillian T Baron
(JT)
Susan L F McLellan
(SLF)
Lucas S Blanton
(LS)
Justin B Seashore
(JB)
C Buddy Creech
(CB)
Todd W Rice
(TW)
Shannon Walker
(S)
Isaac P Thomsen
(IP)
Diego Lopez de Castilla
(D)
Jason W Van Winkle
(JW)
Francis X Riedo
(FX)
Surinder Kaur Pada
(SK)
Alvin D Y Wang
(ADY)
Li Lin
(L)
Michelle Harkins
(M)
Gregory Mertz
(G)
Nestor Sosa
(N)
Louis Yi Ann Chai
(LYA)
Paul Anantharajah Tambyah
(PA)
Sai Meng Tham
(SM)
Sophia Archuleta
(S)
Gabriel Yan
(G)
David A Lindholm
(DA)
Ana Elizabeth Markelz
(AE)
Katrin Mende
(K)
Richard Mularski
(R)
Elizabeth Hohmann
(E)
Mariam Torres-Soto
(M)
Nikolaus Jilg
(N)
Ryan C Maves
(RC)
Gregory C Utz
(GC)
Sarah L George
(SL)
Daniel F Hoft
(DF)
James D Brien
(JD)
Roger Paredes
(R)
Lourdes Mateu
(L)
Cora Loste
(C)
Princy Kumar
(P)
Sarah Thornton
(S)
Sharmila Mohanraj
(S)
Noreen A Hynes
(NA)
Lauren M Sauer
(LM)
Christopher J Colombo
(CJ)
Christina Schofield
(C)
Rhonda E Colombo
(RE)
Susan E Chambers
(SE)
Richard M Novak
(RM)
Andrea Wendrow
(A)
Samir K Gupta
(SK)
Tida Lee
(T)
Tahaniyat Lalani
(T)
Mark Holodniy
(M)
Aarthi Chary
(A)
Nikhil Huprikar
(N)
Anuradha Ganesan
(A)
Norio Ohmagari
(N)
Ayako Mikami
(A)
D Ashley Price
(DA)
Christopher J A Duncan
(CJA)
Kerry Dierberg
(K)
Henry J Neumann
(HJ)
Stephanie N Taylor
(SN)
Alisha Lacour
(A)
Najy Masri
(N)
Edwin Swiatlo
(E)
Kyle Widmer
(K)
James D Neaton
(JD)
Mary Bessesen
(M)
David S Stephens
(DS)
Timothy H Burgess
(TH)
Timothy M Uyeki
(TM)
Robert Walker
(R)
G Lynn Marks
(GL)
Anu Osinusi
(A)
Huyen Cao
(H)
Anabela Cardoso
(A)
Stephanie de Bono
(S)
Douglas E Schlichting
(DE)
Kevin K Chung
(KK)
Jennifer L Ferreira
(JL)
Michelle Green
(M)
Mat Makowski
(M)
Michael R Wierzbicki
(MR)
Tom M Conrad
(TM)
Jill Ann El-Khorazaty
(JA)
Heather Hill
(H)
Tyler Bonnett
(T)
Nikki Gettinger
(N)
Theresa Engel
(T)
Teri Lewis
(T)
Jing Wang
(J)
John H Beigel
(JH)
Kay M Tomashek
(KM)
Varduhi Ghazaryan
(V)
Tatiana Beresnev
(T)
Seema Nayak
(S)
Lori E Dodd
(LE)
Walla Dempsey
(W)
Effie Nomicos
(E)
Marina Lee
(M)
Rhonda Pikaart-Tautges
(R)
Mohamed Elsafy
(M)
Robert Jurao
(R)
Hyung Koo
(H)
Michael Proschan
(M)
Tammy Yokum
(T)
Janice Arega
(J)
Ruth Florese
(R)
Jocelyn D Voell
(JD)
Richard Davey
(R)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Massachusetts Medical Society.