Long-term outcomes of passive immunotherapy for COVID-19: A pooled analysis of a large multinational platform randomized clinical trial.

IF 10.9 1区医学 Q1 INFECTIOUS DISEASES Clinical Microbiology and Infection Pub Date : 2025-02-06 DOI:10.1016/j.cmi.2025.02.002

Ahmad Mourad, Gregory A Grandits, Lianne K Siegel, Nicole Engen, Christina Barkauskas, Nnakelu Eriobu, Mamta Jain, Tomas O Jensen, Adit Ginde, Elizabeth Higgs, Daniel B Knox, Jonathan Kitonsa, Kami Kim, Jakob J Malin, Vasiliki Rapti, D Ashley Price, Alfredo J Mena Lora, Gail Mathews, Eleftherios Mylonakis, Thomas A Murray, Uriel Sandkovsky, Roger Paredes, Srikanth Ramachandruni, Cavan Reilly, David Vock, John C Williamson, Barnaby Edward Young, Wesley H Self, Jens Lundgren, Thomas L Holland

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引用次数: 0

Abstract

Objectives: Passive immunotherapy, including monoclonal antibodies and neutralizing proteins, were used for the treatment of patients with COVID-19 during the pandemic. 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 versus placebo through 18 months.

Results: A total of 2311 participants were enrolled between December 16^th, 2020 and November 15^th, 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 enrollment was 8 days (IQR 6 - 10), and most participants received remdesivir (92.1% [2129/2311]) and corticosteroids (70.4% [1627/2311]) prior to enrollment. There was no difference in mortality across all active (11.9% [157/1315]) versus placebo (14.0% [139/996]) arms (HR 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]) versus placebo (32.1% [320/996]) arms (HR 0.96 [95% CI 0.84 - 1.10]).

Conclusions: 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.

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来源期刊

Clinical Microbiology and Infection 医学-传染病学

CiteScore

25.30

自引率

2.10%

发文量

441

审稿时长

2-4 weeks

期刊介绍： Clinical Microbiology and Infection (CMI) is a monthly journal published by the European Society of Clinical Microbiology and Infectious Diseases. It focuses on peer-reviewed papers covering basic and applied research in microbiology, infectious diseases, virology, parasitology, immunology, and epidemiology as they relate to therapy and diagnostics.