Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe COVID-19

How to cite: Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe COVID-19 outcomes in non-hospitalised patients: an observational cohort study using the OpenSAFELY platform Bang Zheng, Amelia CA Green, John Tazare, Helen J Curtis, Louis Fisher, Linda Nab, Anna Schultze, Viyaasan Mahalingasivam, Edward PK Parker, William J Hulme, Sebastian CJ Bacon, Nicholas J DeVito, Christopher Bates, David Evans, Peter Inglesby, Henry Drysdale, Simon Davy, Jonathan Cockburn, Caroline E Morton, George Hickman, Tom Ward, Rebecca M Smith, John Parry, Frank Hester, Sam Harper, Amir Mehrkar, Rosalind M Eggo, Alex J Walker, Stephen JW Evans, Ian J Douglas, Brian MacKenna, Ben Goldacre, Laurie A Tomlinson medRxiv 2022.05.22.22275417; doi: https://doi.org/10.1101/2022.05.22.22275417

Abstract

Objective: To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) vs. molnupiravir (an antiviral) in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients. Design: With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform.

Setting: Patient-level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on COVID-19 infection and therapeutics, hospital admission and death within the OpenSAFELY-TPP platform, covering a period where both medications were frequently prescribed in community settings.

Participants: Non-hospitalised adult COVID-19 patients at high-risk of severe outcomes treated with sotrovimab or molnupiravir between December 16, 2021 and February 10, 2022.

Interventions: Sotrovimab or molnupiravir administered in the community by COVID-19 Medicine Delivery Units.

Main outcome measure: COVID-19 related hospitalisation or COVID-19 related death within 28 days after treatment initiation.

Results: Patients treated with sotrovimab (n=3288) and molnupiravir (n=2663) were similar with respect to most baseline characteristics. The mean age of all 5951 patients was 52 (SD=16) years; 59% were female, 89% White and 87% had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 84 (1.4%) COVID-19 related hospitalisations/deaths were observed (31 treated with sotrovimab and 53 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio, HR=0.53, 95% CI: 0.32-0.88; P=0.014). Consistent results were obtained from propensity score weighted Cox models (HR=0.51, 95% CI: 0.31-0.83; P=0.007) and when restricted to fully vaccinated people (HR=0.52, 95% CI: 0.30-0.90; P=0.020). No substantial effect modifications by other characteristics were detected (all P values for interaction>0.10).

Conclusion: In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, those who received sotrovimab were at lower risk of severe COVID-19 outcomes than those receiving molnupiravir.