Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA)
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Tocilizumab in patients hospitalised with COVID-19 pneumonia : Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA). / Rosas, Ivan O.; Bräu, Norbert; Waters, Michael; Go, Ronaldo C.; Malhotra, Atul; Hunter, Bradley D.; Bhagani, Sanjay; Skiest, Daniel; Savic, Sinisa; Douglas, Ivor S.; Garcia-Diaz, Julia; Aziz, Mariam S.; Cooper, Nichola; Youngstein, Taryn; Sorbo, Lorenzo Del; De La Zerda, David J.; Ustianowski, Andrew; Gracian, Antonio Cubillo; Blyth, Kevin G.; Carratalà, Jordi; François, Bruno; Benfield, Thomas; Haslem, Derrick; Bonfanti, Paolo; van der Leest, Cor H.; Rohatgi, Nidhi; Wiese, Lothar; Luyt, Charles Edouard; Bauer, Rebecca N.; Cai, Fang; Lee, Ivan T.; Matharu, Balpreet; Metcalf, Louis; Wildum, Steffen; Graham, Emily; Tsai, Larry; Bao, Min.
In: EClinicalMedicine, Vol. 47, 101409, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Tocilizumab in patients hospitalised with COVID-19 pneumonia
T2 - Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA)
AU - Rosas, Ivan O.
AU - Bräu, Norbert
AU - Waters, Michael
AU - Go, Ronaldo C.
AU - Malhotra, Atul
AU - Hunter, Bradley D.
AU - Bhagani, Sanjay
AU - Skiest, Daniel
AU - Savic, Sinisa
AU - Douglas, Ivor S.
AU - Garcia-Diaz, Julia
AU - Aziz, Mariam S.
AU - Cooper, Nichola
AU - Youngstein, Taryn
AU - Sorbo, Lorenzo Del
AU - De La Zerda, David J.
AU - Ustianowski, Andrew
AU - Gracian, Antonio Cubillo
AU - Blyth, Kevin G.
AU - Carratalà, Jordi
AU - François, Bruno
AU - Benfield, Thomas
AU - Haslem, Derrick
AU - Bonfanti, Paolo
AU - van der Leest, Cor H.
AU - Rohatgi, Nidhi
AU - Wiese, Lothar
AU - Luyt, Charles Edouard
AU - Bauer, Rebecca N.
AU - Cai, Fang
AU - Lee, Ivan T.
AU - Matharu, Balpreet
AU - Metcalf, Louis
AU - Wildum, Steffen
AU - Graham, Emily
AU - Tsai, Larry
AU - Bao, Min
N1 - Publisher Copyright: © 2022 The Author(s)
PY - 2022
Y1 - 2022
N2 - Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated. Methods: Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615. Findings: By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference –0·5% [95% CI –9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase–quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti–SARS-CoV-2 antibodies at day 60. Interpretation: There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments. Funding: F. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C.
AB - Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated. Methods: Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615. Findings: By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference –0·5% [95% CI –9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase–quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti–SARS-CoV-2 antibodies at day 60. Interpretation: There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments. Funding: F. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C.
KW - Coronavirus disease 2019
KW - Interleukin-6
KW - Randomised controlled trial
KW - Severe acute respiratory syndrome coronavirus-2
KW - Tocilizumab
KW - Viral load
U2 - 10.1016/j.eclinm.2022.101409
DO - 10.1016/j.eclinm.2022.101409
M3 - Journal article
C2 - 35475258
AN - SCOPUS:85136251056
VL - 47
JO - EClinicalMedicine
JF - EClinicalMedicine
SN - 2589-5370
M1 - 101409
ER -
ID: 326672164