Dose-dependent impact of tixagevimab-cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals

tixagevimab-cilgavimab 作为 SARS-CoV-2 一级预防药物在免疫功能低下人群中的剂量依赖性影响

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Abstract

Tixagevimab-cilgavimab was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevention from December 2021 to January 2023, with dosing changes to reflect circulating variants. In a retrospective analysis of 597 immunocompromised individuals, incidence of SARS-CoV-2 infection was compared between those who did and did not receive tixagevimab-cilgavimab. A proportional hazards regression model with a time-dependent regressor for tixagevimab-cilgavimab dose was applied to assess cumulative doses. Secondary analyses were performed in hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor (CAR)-T cell therapy recipients. There was no difference in SARS-CoV-2 infections between tixagevimab-cilgavimab recipients and controls (p = 0.27). There was a trend towards protection with increasing dose from 150 (HR 0.83, CI 0.50-1.38) to 600 mg (HR 0.48, CI 0.06-3.63) when truncating data on November 1st, 2022, which was also seen in HSCT or CAR-T cell therapy recipients, 150 mg (HR 0.71, CI 0.31-1.65) to 600 mg (HR 0.26, CI 0.01-7.47). This was most evident in immunocompromised individuals when variants neutralized by tixagevimab-cilgavimab in vitro were circulating; effectiveness 74%. Supports a proof of concept for monoclonal antibodies in immunocompromised individuals as a prevention strategy against novel viruses.

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