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.

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. Observational cohort study with the OpenSAFELY platform. 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. 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. Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units. 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. 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. 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.

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Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from UK Research and Innovation (UKRI), National Institute for Health Research (NIHR), and Asthma UK-British Lung Foundation (BLF) for the submitted work; BG has received research funding from the Laura and John Arnold Foundation, NHS NIHR, NIHR School of Primary Care Research, NHS England, NIHR Oxford Biomedical Research Centre, Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, Wellcome Trust, Good Thinking Foundation, Health Data Research UK, Health Foundation, World Health Organization, UKRI MRC, Asthma UK, British Lung Foundation, and Longitudinal Health and Wellbeing strand of the National Core Studies programme; BG is a non-executive director at NHS Digital; BG also receives personal income from speaking and writing for lay audiences on the misuse of science; IJD has received unrestricted research grants and holds shares in GlaxoSmithKline (GSK); LAT has received funding from Medical Research Council (MRC), Wellcome, NIHR, consulted for Bayer in relation to an observational study of chronic kidney disease (unpaid), and is a member of four non-industry funded (NIHR/MRC) trial advisory committees (unpaid) and Medicines and Healthcare products Regulatory Agency (MHRA) expert advisory group (Women’s Health); NJD has received funding for covid meta-research from the Federal Ministry of Education and Research (BMBF, Germany); JT is funded at the London School of Hygiene and Tropical Medicine (LSHTM) through an unrestricted grant from GSK; AM was a former employee and interim chief medical officer of NHS Digital and is a member of Royal College of General Practitioners (RCGP) health informatics group and the NHS Digital GP data Professional Advisory Group; AS is employed by LSHTM on a fellowship sponsored by GSK; VM has received funding from National Institute for Health and Care Research (NIHR301535); RME has received funding from HDR UK (MR/S003975/1); no other relationships or activities that could appear to have influenced the submitted work.