TY - JOUR
T1 - Long-term outcomes of passive immunotherapy for COVID-19
T2 - A pooled analysis of a large multinational platform randomized clinical trial
AU - Mourad, Ahmad
AU - Grandits, Gregory A
AU - Siegel, Lianne K
AU - Engen, Nicole
AU - Barkauskas, Christina
AU - Eriobu, Nnakelu
AU - Jain, Mamta
AU - Jensen, Tomas O
AU - Ginde, Adit
AU - Higgs, Elizabeth
AU - Knox, Daniel B
AU - Kitonsa, Jonathan
AU - Kim, Kami
AU - Malin, Jakob J
AU - Rapti, Vasiliki
AU - Price, D Ashley
AU - Mena Lora, Alfredo J
AU - Mathews, Gail
AU - Mylonakis, Eleftherios
AU - Murray, Thomas A
AU - Sandkovsky, Uriel
AU - Paredes, Roger
AU - Ramachandruni, Srikanth
AU - Reilly, Cavan
AU - Vock, David
AU - Williamson, John C
AU - Young, Barnaby Edward
AU - Self, Wesley H
AU - Lundgren, Jens
AU - Holland, Thomas L
AU - INSIGHT ACTIV-3/TICO Study Group and the STRIVE Network
N1 - Copyright © 2025. Published by Elsevier Ltd.
PY - 2025/6
Y1 - 2025/6
N2 - OBJECTIVES: Passive immunotherapy, including monoclonal antibodies and neutralizing proteins, was used for the treatment of patients with COVID-19 during the pandemic. Accelerating COVID-19 Therapeutic Interventions and Vaccines-Therapeutics for Inpatients with COVID-19 (ACTIV-3/TICO) was a multinational, randomized placebo-controlled platform trial that evaluated the effectiveness of multiple passive immunotherapy agents in patients hospitalized with COVID-19. Given the long half-life of some agents studied, participants were followed for an extended period to assess the long-term efficacy and sustained safety of these agents.METHODS: We conducted a pooled analysis of individual participant data from four trials of ACTIV-3/TICO: sotrovimab, amubarvimab-romlusevimab, tixagevimab-cilgavimab, and ensovibep. Cox proportional hazards models were conducted to compare time to mortality and time to mortality or rehospitalization between participants receiving active agents vs. placebo through 18 months.RESULTS: A total of 2311 participants were enrolled between 16 December 2020 and 15 November 2021. Overall, 56.9% (1315/2311) received an active agent and 77.2% (1784/2311) of participants were unvaccinated for SARS-CoV-2. Median duration between symptom onset and enrolment was 8 days (interquartile range, 6-10), and most participants received remdesivir (92.1% [2129/2311]) and corticosteroids (70.4% [1627/2311]) before enrolment. There was no difference in mortality across all active (11.9% [157/1315]) vs. placebo (14.0% [139/996]) arms (hazard ratio, 0.87; 95% CI, 0.70-1.08). Furthermore, there was no difference in combined mortality or rehospitalization across all active (31.7% [417/1315]) vs. placebo (32.1% [320/996]) arms (hazard ratio, 0.96; 95% CI, 0.84-1.10).DISCUSSION: In our large study of long half-life passive immunotherapy for hospitalized patients with COVID-19, we did not find evidence of a long-term effect on either mortality or rehospitalization.TRIAL REGISTRATION: NCT04501978.
AB - OBJECTIVES: Passive immunotherapy, including monoclonal antibodies and neutralizing proteins, was used for the treatment of patients with COVID-19 during the pandemic. Accelerating COVID-19 Therapeutic Interventions and Vaccines-Therapeutics for Inpatients with COVID-19 (ACTIV-3/TICO) was a multinational, randomized placebo-controlled platform trial that evaluated the effectiveness of multiple passive immunotherapy agents in patients hospitalized with COVID-19. Given the long half-life of some agents studied, participants were followed for an extended period to assess the long-term efficacy and sustained safety of these agents.METHODS: We conducted a pooled analysis of individual participant data from four trials of ACTIV-3/TICO: sotrovimab, amubarvimab-romlusevimab, tixagevimab-cilgavimab, and ensovibep. Cox proportional hazards models were conducted to compare time to mortality and time to mortality or rehospitalization between participants receiving active agents vs. placebo through 18 months.RESULTS: A total of 2311 participants were enrolled between 16 December 2020 and 15 November 2021. Overall, 56.9% (1315/2311) received an active agent and 77.2% (1784/2311) of participants were unvaccinated for SARS-CoV-2. Median duration between symptom onset and enrolment was 8 days (interquartile range, 6-10), and most participants received remdesivir (92.1% [2129/2311]) and corticosteroids (70.4% [1627/2311]) before enrolment. There was no difference in mortality across all active (11.9% [157/1315]) vs. placebo (14.0% [139/996]) arms (hazard ratio, 0.87; 95% CI, 0.70-1.08). Furthermore, there was no difference in combined mortality or rehospitalization across all active (31.7% [417/1315]) vs. placebo (32.1% [320/996]) arms (hazard ratio, 0.96; 95% CI, 0.84-1.10).DISCUSSION: In our large study of long half-life passive immunotherapy for hospitalized patients with COVID-19, we did not find evidence of a long-term effect on either mortality or rehospitalization.TRIAL REGISTRATION: NCT04501978.
KW - COVID-19
KW - Monoclonal antibodies
KW - Neutralizing antibodies
KW - Passive immunotherapy
KW - SARS-CoV-2
KW - COVID-19 Drug Treatment
KW - Immunization, Passive/methods
KW - Humans
KW - Middle Aged
KW - Antibodies, Neutralizing/therapeutic use
KW - Antibodies, Monoclonal/therapeutic use
KW - Male
KW - Treatment Outcome
KW - Randomized Controlled Trials as Topic
KW - SARS-CoV-2/immunology
KW - Female
KW - Adult
KW - Aged
KW - COVID-19/therapy
UR - http://www.scopus.com/inward/record.url?scp=85219010736&partnerID=8YFLogxK
U2 - 10.1016/j.cmi.2025.02.002
DO - 10.1016/j.cmi.2025.02.002
M3 - Journal article
C2 - 39922466
SN - 1198-743X
VL - 31
SP - 1053
EP - 1060
JO - Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
JF - Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
IS - 6
ER -