The safety of antivirals and neutralising monoclonal antibodies used in prehospital treatment of Covid-19

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Abstract

Objective

This proof-of-principle pharmacovigilance study used Electronic Health Record (EHR) data to examine the safety of sotrovimab, paxlovid and molnupiravir in prehospital treatment of Covid-19.

Method

With NHS England approval, we conducted an observational cohort study using OpenSAFELY-TPP, a secure software-platform which executes analyses across EHRs for 24 million people in England. High-risk individuals with Covid-19 eligible for prehospital treatment were included. Adverse events (AEs) were categorised into events in the drug’s Summary of Product Characteristics (SmPC), drug-reactions and immune-mediated. Cox models compared risk across treatments. A pre-pandemic record analysis was performed for comparative purposes.

Results

Between 2021-2023, 37,449 patients received sotrovimab, paxlovid or molnupiravir whilst 109,647 patients made up an eligible-but-untreated population. The 29-day rates of AEs were low: SmPC 0.34 per 1000 patient-years (95%CI 0.32-0.36); drug-reactions 0.01(95% CI0.01-0.02) and immune-mediated 0.03(95%CI 0.03-0.04), and similar or lower than the pre-pandemic period. Compared with the eligible but untreated population, sotrovimab and paxlovid associated with a risk of SmPC AE [adjHR 1.36(95%CI 1.15-1.62) and 1.28(95%CI 1.05-1.55), respectively], whilst sotrovimab associated with a risk of drug-reactions [adjHR 2.95(95%CI 1.56-5.55)] and immune-mediated events [adjHR 3.22(95%CI 1.86-5.57)].

Conclusion

Sotrovimab, paxlovid and molnupiravir demonstrate acceptable safety profiles. Although the risk of AEs was greatest with sotrovimab, event rates were lower than comparative pre-pandemic period.

Article activity feed

  1. Chengxi Zang

    Review 2: "The Safety of Antivirals and Neutralising Monoclonal Antibodies Used in Prehospital Treatment of Covid-19"

    Reviewers emphasize addressing potential confounding factors and providing more comprehensive methodological details for stronger conclusions.

  2. Phyo Htoo

    Review 1: "The Safety of Antivirals and Neutralising Monoclonal Antibodies Used in Prehospital Treatment of Covid-19"

    Reviewers emphasize addressing potential confounding factors and providing more comprehensive methodological details for stronger conclusions.