Effectiveness of Sotrovimab and Molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages
Effectiveness of sotrovimab and molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform
How to cite: John Tazare, Linda Nab, Bang Zheng, William J Hulme, Amelia C A Green, Helen J Curtis, Viyaasan Mahalingasivam, Rose Higgins, Anna Schultze, Krishnan Bhaskaran, Amir Mehrkar, Andrea L Schaffer, Rebecca M Smith, Christopher Bates, Jonathan Cockburn, John Parry, Frank Hester, Sam Harper, Rosalind M Eggo, Alex J Walker, Michael Marks, Mike Brown, Camille Maringe, Clémence Leyrat, Stephen J W Evans, Ben Goldacre, Brian MacKenna, Jonathan A C Sterne, Laurie A Tomlinson, Ian J Douglas. Effectiveness of Sotrovimab and Molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform. medRxiv 2023. DOI:10.1101/2023.05.12.23289914
Abstract
Background
The effectiveness of COVID-19 monoclonal antibody and antiviral therapies against severe COVID-19 outcomes is unclear. Initial benefit was shown in unvaccinated patients and before the Omicron variant emerged. We used the OpenSAFELY platform to emulate target trials to estimate the effectiveness of sotrovimab or molnupiravir, versus no treatment.
Methods
With the approval of NHS England, we derived population-based cohorts of non-hospitalised high-risk individuals in England testing positive for SARS-CoV-2 during periods of dominance of the BA.1 (16/12/2021-10/02/2022) and BA.2 (11/02/2022-21/05/2022) Omicron sublineages. We used the clone-censor-weight approach to estimate the effect of treatment with sotrovimab or molnupiravir initiated within 5 days after positive test versus no treatment. Hazard ratios (HR) for COVID-19 hospitalisation or death within 28 days were estimated using weighted Cox models.
Results
Of the 35,856 [BA.1 period] and 39,192 [BA.2 period] patients, 1,830 [BA.1] and 1,242 [BA.2] were treated with molnupiravir and 2,244 [BA.1] and 4,164 [BA.2] with sotrovimab. The estimated HRs for molnupiravir versus untreated were 1.00 (95%CI: 0.81;1.22) [BA.1] and 1.22 (0.96;1.56) [BA.2]; corresponding HRs for sotrovimab versus untreated were 0.76 (0.66;0.89) [BA.1] and 0.92 (0.79;1.06) [BA.2].
Conclusions
Compared with no treatment, sotrovimab was associated with reduced risk of adverse outcomes after COVID-19 in the BA.1 period, but there was weaker evidence of benefit in the BA2 period. Molnupiravir was not associated with reduced risk in either period.