Efficacy and safety of baricitinib in hospitalized adults with
severe or critical COVID-19 (Bari-SolidAct): a randomised,
double-blind, placebo-controlled phase 3 trial

J 2023

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

TROSEID, Marius, Jose R ARRIBAS, Lambert ASSOUMOU, Aleksander Rygh HOLTEN, Julien POISSY et. al.

Basic information

Original name

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

Authors

Edition

Critical Care, London, BioMed Central Ltd, 2023, 1364-8535

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30230 Other clinical medicine subjects

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

SolidAct

Impact factor

Impact factor: 15.100 in 2022

RIV identification code

RIV/00216224:90249/23:00130073

DOI

http://dx.doi.org/10.1186/s13054-022-04205-8

UT WoS

000992268000002

Keywords (in Czech)

COVID-19; immunomodulator; safety; baricitinib; JAK inhibitor

Keywords in English

COVID-19; Vaccination; Safety; Baricitinib

Abstract

V originále

Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants.Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures.Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8 center dot 3 to 8 center dot 0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities.Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies.

Links

90249, large research infrastructures

Name: CZECRIN IV

Citovat

TROSEID, Marius, Jose R ARRIBAS, Lambert ASSOUMOU, Aleksander Rygh HOLTEN, Julien POISSY, Vida TERZIC, Fulvia MAZZAFERRI, Rodriguez Bano JESUS, Joe EUSTACE, Maya HITES, Michael JOANNIDIS, Jose-Artur PAIVA, Jean REUTER, Isabel PUENTMANN, Thale D J H PATRICK-BROWN, Elin WESTERHEIM, Katerina NEZVALOVA-HENRIKSEN, Lydie BENIGUEL, Tuva Borresdatter DAHL, Maude BOUSCAMBERT, Monika HALANOVA, Zoltan PETERFI, Sotirios TSIODRAS, Michael REZEK, Matthias BRIEL, Serhat UNAL, Martin SCHLEGEL, Florence ADER, Karine LACOMBE, Cecilie Delphin AMDAL, Serge RODRIGUES, Kristian TONBY, Alexandre GAUDET, Lars HEGGELUND, Joy MOOTIEN, Asgeir JOHANNESSEN, Jannicke Horjen MOLLER, Diaz Pollan BEATRIZ, Anders Aune TVEITA, Anders Benjamin KILDAL, Jean-Christophe RICHARD, Olav DALGARD, Victoria Charlotte SIMENSEN, Aliou BALDE, de Gastines LUCIE, del Alamo MARTA, Burc AYDIN, Fridtjof LUND-JOHANSEN, Mary-Anne TRABAUD, Alpha DIALLO, Bente HALVORSEN, John-Arne ROTTINGEN, Evelina TACCONELLI, Yazdan YAZDANPANAH, Inge C OLSEN and Dominique COSTAGLIOLA. Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial (Efficacy and Safety of Baricitinib for the Treatment of Hospitalized Adults with Severe or Critical COVID-19 (Bari-SolidAct): A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Trial.). Critical Care. London: BioMed Central Ltd, 2023, vol. 27, No 1, p. 1-15. ISSN 1364-8535. Available from: https://dx.doi.org/10.1186/s13054-022-04205-8.

@article{2233339,
   author = {Troseid, Marius and Arribas, Jose R and Assoumou, Lambert and Holten, Aleksander Rygh and Poissy, Julien and Terzic, Vida and Mazzaferri, Fulvia and Jesus, Rodriguez Bano and Eustace, Joe and Hites, Maya and Joannidis, Michael and Paiva, JoseandArtur and Reuter, Jean and Puentmann, Isabel and PatrickandBrown, Thale D J H and Westerheim, Elin and NezvalovaandHenriksen, Katerina and Beniguel, Lydie and Dahl, Tuva Borresdatter and Bouscambert, Maude and Halanova, Monika and Peterfi, Zoltan and Tsiodras, Sotirios and Rezek, Michael and Briel, Matthias and Unal, Serhat and Schlegel, Martin and Ader, Florence and Lacombe, Karine and Amdal, Cecilie Delphin and Rodrigues, Serge and Tonby, Kristian and Gaudet, Alexandre and Heggelund, Lars and Mootien, Joy and Johannessen, Asgeir and Moller, Jannicke Horjen and Beatriz, Diaz Pollan and Tveita, Anders Aune and Kildal, Anders Benjamin and Richard, JeanandChristophe and Dalgard, Olav and Simensen, Victoria Charlotte and Balde, Aliou and Lucie, de Gastines and Marta, del Alamo and Aydin, Burc and LundandJohansen, Fridtjof and Trabaud, MaryandAnne and Diallo, Alpha and Halvorsen, Bente and Rottingen, JohnandArne and Tacconelli, Evelina and Yazdanpanah, Yazdan and Olsen, Inge C and Costagliola, Dominique},
   article_location = {London},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s13054-022-04205-8},
   keywords = {COVID-19; Vaccination; Safety; Baricitinib},
   language = {eng},
   issn = {1364-8535},
   journal = {Critical Care},
   title = {Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial},
   url = {https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4172086},
   volume = {27},
   year = {2023}
}

TY  - JOUR
ID  - 2233339
AU  - Troseid, Marius - Arribas, Jose R - Assoumou, Lambert - Holten, Aleksander Rygh - Poissy, Julien - Terzic, Vida - Mazzaferri, Fulvia - Jesus, Rodriguez Bano - Eustace, Joe - Hites, Maya - Joannidis, Michael - Paiva, Jose-Artur - Reuter, Jean - Puentmann, Isabel - Patrick-Brown, Thale D J H - Westerheim, Elin - Nezvalova-Henriksen, Katerina - Beniguel, Lydie - Dahl, Tuva Borresdatter - Bouscambert, Maude - Halanova, Monika - Peterfi, Zoltan - Tsiodras, Sotirios - Rezek, Michael - Briel, Matthias - Unal, Serhat - Schlegel, Martin - Ader, Florence - Lacombe, Karine - Amdal, Cecilie Delphin - Rodrigues, Serge - Tonby, Kristian - Gaudet, Alexandre - Heggelund, Lars - Mootien, Joy - Johannessen, Asgeir - Moller, Jannicke Horjen - Beatriz, Diaz Pollan - Tveita, Anders Aune - Kildal, Anders Benjamin - Richard, Jean-Christophe - Dalgard, Olav - Simensen, Victoria Charlotte - Balde, Aliou - Lucie, de Gastines - Marta, del Alamo - Aydin, Burc - Lund-Johansen, Fridtjof - Trabaud, Mary-Anne - Diallo, Alpha - Halvorsen, Bente - Rottingen, John-Arne - Tacconelli, Evelina - Yazdanpanah, Yazdan - Olsen, Inge C - Costagliola, Dominique
PY  - 2023
TI  - Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial
JF  - Critical Care
VL  - 27
IS  - 1
SP  - 1-15
EP  - 1-15
PB  - BioMed Central Ltd
SN  - 13648535
KW  - COVID-19
KW  - Vaccination
KW  - Safety
KW  - Baricitinib
UR  - https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4172086
N2  - Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants.Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures.Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49-69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI - 0.1% [- 8 center dot 3 to 8 center dot 0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (- 3.2% [- 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities.Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies.
ER  -

TROSEID, Marius, Jose R ARRIBAS, Lambert ASSOUMOU, Aleksander Rygh HOLTEN, Julien POISSY, Vida TERZIC, Fulvia MAZZAFERRI, Rodriguez Bano JESUS, Joe EUSTACE, Maya HITES, Michael JOANNIDIS, Jose-Artur PAIVA, Jean REUTER, Isabel PUENTMANN, Thale D J H PATRICK-BROWN, Elin WESTERHEIM, Katerina NEZVALOVA-HENRIKSEN, Lydie BENIGUEL, Tuva Borresdatter DAHL, Maude BOUSCAMBERT, Monika HALANOVA, Zoltan PETERFI, Sotirios TSIODRAS, Michael REZEK, Matthias BRIEL, Serhat UNAL, Martin SCHLEGEL, Florence ADER, Karine LACOMBE, Cecilie Delphin AMDAL, Serge RODRIGUES, Kristian TONBY, Alexandre GAUDET, Lars HEGGELUND, Joy MOOTIEN, Asgeir JOHANNESSEN, Jannicke Horjen MOLLER, Diaz Pollan BEATRIZ, Anders Aune TVEITA, Anders Benjamin KILDAL, Jean-Christophe RICHARD, Olav DALGARD, Victoria Charlotte SIMENSEN, Aliou BALDE, de Gastines LUCIE, del Alamo MARTA, Burc AYDIN, Fridtjof LUND-JOHANSEN, Mary-Anne TRABAUD, Alpha DIALLO, Bente HALVORSEN, John-Arne ROTTINGEN, Evelina TACCONELLI, Yazdan YAZDANPANAH, Inge C OLSEN and Dominique COSTAGLIOLA. Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial (Efficacy and Safety of Baricitinib for the Treatment of Hospitalized Adults with Severe or Critical COVID-19 (Bari-SolidAct): A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Trial.). \textit{Critical Care}. London: BioMed Central Ltd, 2023, vol.~27, No~1, p.~1-15. ISSN~1364-8535. Available from: https://dx.doi.org/10.1186/s13054-022-04205-8.

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