Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform
Authors: Zheng Bang , Green Amelia C A , Tazare John , Curtis Helen J , Fisher Louis , Nab Linda , Schultze Anna , Mahalingasivam Viyaasan , Parker Edward P K , Hulme William J , Bacon Sebastian C J , DeVito Nicholas J , Bates Christopher , Evans David , Inglesby Peter , Drysdale Henry , Davy Simon , Cockburn Jonathan , Morton Caroline E , Hickman George , Ward Tom , Smith Rebecca M , Parry John , Hester Frank , Harper Sam , Mehrkar Amir , Eggo Rosalind M , Walker Alex J , Evans Stephen J W , Douglas Ian J , MacKenna Brian , Goldacre Ben , Tomlinson Laurie A 
Published: November 2022

Abstract

Objective
To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19.

Design
Observational cohort study with the OpenSAFELY platform.

Setting
With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and 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 SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings.

Participants
Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.

Interventions
Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units.

Main outcome measures
Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment.

Results
Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, 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 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England.

Conclusions
In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.