TY - JOUR
T1 - Early Treatment with Pegylated Interferon Lambda for Covid-19
AU - Reis, Gilmar
AU - Moreira Silva, Eduardo A.S.
AU - Medeiros Silva, Daniela C.
AU - Thabane, Lehana
AU - Campos, Vitoria H.S.
AU - Ferreira, Thiago S.
AU - Santos, Castilho V.Q.
AU - Nogueira, Ana M.R.
AU - Almeida, Ana P.F.G.
AU - Savassi, Leonardo C.M.
AU - Figueiredo-Neto, Adhemar D.
AU - Dias, Ana C.F.
AU - Freire Júnior, Adelino M.
AU - Bitarães, Carina
AU - Milagres, Aline C.
AU - Callegari, Eduardo D.
AU - Simplicio, Maria I.C.
AU - Ribeiro, Luciene B.
AU - Oliveira, Rosemary
AU - Harari, Ofir
AU - Wilson, Lindsay A.
AU - Forrest, Jamie I.
AU - Ruton, Hinda
AU - Sprague, Sheila
AU - Mckay, Paula
AU - Guo, Christina M.
AU - Limbrick-Oldfield, Eve H.
AU - Kanters, Steve
AU - Guyatt, Gordon H.
AU - Rayner, Craig R.
AU - Kandel, Christopher
AU - Biondi, Mia J.
AU - Kozak, Robert
AU - Hansen, Bettina
AU - Zahoor, M. Atif
AU - Arora, Paul
AU - Hislop, Colin
AU - Choong, Ingrid
AU - Feld, Jordan J.
AU - Mills, Edward J.
AU - Glenn, Jeffrey S.
N1 - for the TOGETHER Investigators
Funding Information:
Supported by FastGrants , the Rainwater Charitable Foundation , the Latona Foundation, and Eiger BioPharmaceuticals .
Publisher Copyright:
© 2023 Massachusetts Medical Society.
PY - 2023/2/9
Y1 - 2023/2/9
N2 - Background: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. Methods: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. Results: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results: were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. Conclusions: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo.
AB - Background: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. Methods: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. Results: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results: were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. Conclusions: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo.
UR - http://www.scopus.com/inward/record.url?scp=85149616233&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2209760
DO - 10.1056/NEJMoa2209760
M3 - Article
C2 - 36780676
AN - SCOPUS:85149616233
SN - 0028-4793
VL - 388
SP - 518
EP - 528
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 6
ER -
