{"doi":"10.1016/j.cmi.2025.02.002","title":"Long-term outcomes of passive immunotherapy for COVID-19: a pooled analysis of a large multinational platform randomized clinical trial","abstract":"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. 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