Publication date: Jul 15, 2024

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. 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. 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)]. 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.

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