(246) Effectiveness of Monoclonal Antibodies and Antivirals Against Severe COVID-19 Outcomes in Community Settings in England: An Emulated Target Trial Using the OpenSAFELY Platform

Publication Number: 920

Background: On 16th December 2021, neutralising monoclonal antibodies (nMAbs) and antiviral medicines were offered as treatment to non-hospitalised COVID-19 patients at high risk of severe outcomes in England. Initially, the two most common therapeutic options were sotrovimab (nMAb) and molnupiravir (antiviral). Evidence for the approval of these medications primarily came from two phase 3 randomised placebo-controlled trials. Currently very little is known about real-world COVID-19 treatment effectiveness, especially in more vulnerable populations, such as those eligible for these treatments. In this cohort study, we outline the protocol of a target trial and emulate this using data from the OpenSAFELY platform.

Objectives: To estimate the hazard of COVID-19 related hospitalisation and death within 28 days associated with use of sotrovovimab or molnupiravir versus no-treatment, in non-hospitalised high-risk COVID-19 patients.

Methods: With the approval of NHS England, we analysed primary care data from patients in England using the OpenSAFELY platform linked to hospitalisation, mortality, COVID-19 testing and COVID-19 therapeutics records. We identified all non-hospitalised COVID-19 patients between 16th December 2021 and 10th February 2022, matching patients who initiated sotrovimab and molnupiravir to eligible patients who did not initiate either therapy. Patients were followed from matched date of infection (to mitigate immortal time bias) until the earliest of outcome, death date, deregistration or 28 days post-index date. Propensity score weighting was used to account for confounding bias and treatment effects were obtained using Cox models. A key concern was unmeasured confounding and this was investigated using quantitative bias analysis, including e-values.

Results: Between 16th December 2021 and 10th February 2022, we identified 47,430 patients who were eligible to receive nMABs or antivirals. Of these, 5,951 patients received sotrovimab (55.3%) or molnupiravir (45.7%), within the study period. The mean age of patients receiving treatment was 52.3 and the majority were female (58.8%). Furthermore, 87.4% of treated patients had received 3 or more vaccinations. This is an ongoing study and full results will be presented at the conference.

Conclusions: Real-world evidence of the effectiveness of nMABs and antivirals is essential to support clinical decision making on the use of nMAbs and antirvirals for preventing severe COVID-19 outcomes. In particular, results will help to further contextualise the trial findings by studying treatment effects in a population with high vaccine coverage rates and in the presence of the omicron variant.