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

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.

Effectiveness of Sotrovimab in Preventing COVID-19-related Hospitalizations or Deaths Among U.S. Veterans

“…The copyright holder for this this version posted December 30, 2022. ; https://doi.org/10.1101/2022.12.30.22284063 doi: medRxiv preprint with similar demographics and again among patients on kidney replacement therapy covering BA.2 predominant period in the UK and found sotrovimab to be effective throughout BA.1, BA. 2 and BA.4/5 predominance [20].…”

Real-World Effectiveness of Sotrovimab for the Early Treatment of COVID-19 During SARS-CoV-2 Delta and Omicron Waves in the USA

“…In a real-world study conducted in England among high-risk nonhospitalized patients, treatment with sotrovimab was associated with 46% lower risk [hazard ratio (HR) 0.54, 95% CI 0.33–0.88] of 28-day hospitalization or death during the Omicron BA.1 period (16 December 2021–10 February 2022) and 56% lower risk (HR 0.44, 95% CI 0.27–0.71) during the Omicron BA.2 period (16 February 2022–1 May 2022) compared with treatment with molnupiravir [ 15 ].…”

Characteristics and outcomes of patients with COVID-19 at high-risk of disease progression receiving sotrovimab, oral antivirals or no treatment in England

“…30 The results of this study compliment other recent real-word studies on early treatments for COVID-19 in the UK. [31][32][33] For example, the findings of a recent publication on the comparative effectiveness of sotrovimab versus molnupiravir in England, conducted using the OpenSAFELY platform, showed that sotrovimab treatment was associated with a significant reduction in risk of severe COVID-19 outcomes in comparison to treatment with molnupiravir during BA.1 (primary analysis) and BA.2 (exploratory analysis) predominance. 31 Moreover, sotrovimab was found to offer a similar level of protection against disease progression in patients with COVID-19 infected with the Omicron BA.1 and BA.2 subvariants.…”

“…[31][32][33] For example, the findings of a recent publication on the comparative effectiveness of sotrovimab versus molnupiravir in England, conducted using the OpenSAFELY platform, showed that sotrovimab treatment was associated with a significant reduction in risk of severe COVID-19 outcomes in comparison to treatment with molnupiravir during BA.1 (primary analysis) and BA.2 (exploratory analysis) predominance. 31 Moreover, sotrovimab was found to offer a similar level of protection against disease progression in patients with COVID-19 infected with the Omicron BA.1 and BA.2 subvariants. 32 Similarly, in an observational study in the US, treatment with sotrovimab was associated with a reduced risk of all-cause hospitalisation and mortality during the predominance of early Omicron variants.…”