Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform

Bang Zheng; John Tazare; Linda Nab; Amelia Ca Green; Helen J Curtis; Viyaasan Mahalingasivam; Emily L Herrett; Ruth E Costello; Rosalind M Eggo; Victoria Speed; Sebastian Cj Bacon; Christopher Bates; John Parry; Jonathan Cockburn; Frank Hester; Sam Harper; Andrea L Schaffer; William J Hulme; Amir Mehrkar; Stephen Jw Evans; Brian MacKenna; Ben Goldacre; Ian J Douglas; Laurie A Tomlinson; OpenSAFELY Collaborative

doi:10.1016/j.lanepe.2023.100741

Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform

Lancet Reg Health Eur. 2023 Oct 8:34:100741. doi: 10.1016/j.lanepe.2023.100741. eCollection 2023 Nov.

Authors

Bang Zheng¹, John Tazare¹, Linda Nab², Amelia Ca Green², Helen J Curtis², Viyaasan Mahalingasivam¹, Emily L Herrett¹, Ruth E Costello¹, Rosalind M Eggo¹, Victoria Speed², Sebastian Cj Bacon², Christopher Bates³, John Parry³, Jonathan Cockburn³, Frank Hester³, Sam Harper³, Andrea L Schaffer², William J Hulme², Amir Mehrkar², Stephen Jw Evans¹, Brian MacKenna², Ben Goldacre², Ian J Douglas¹, Laurie A Tomlinson¹; OpenSAFELY Collaborative

Affiliations

¹ London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
² Nuffield Department of Primary Care Health Sciences, Bennett Institute for Applied Data Science, University of Oxford, Oxford OX2 6GG, UK.
³ TPP, TPP House, 129 Low Lane, Horsforth, Leeds LS18 5PX, UK.

Abstract

Background: Timely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed to compare the effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients during Omicron waves.

Methods: With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people in England and were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death, covering a period where both nirmatrelvir/ritonavir and sotrovimab were first-line treatment options in community settings (February 10, 2022-November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator to nirmatrelvir/ritonavir, both of which were antivirals. Cox proportional hazards model stratified by area was used to compare the risk of 28-day COVID-19 related hospitalisation/death across treatment groups.

Findings: A total of 9026 eligible patients treated with nirmatrelvir/ritonavir (n = 5704) and sotrovimab (n = 3322) were included in the main analysis. The mean age was 52.7 (SD = 14.9) years and 93% (8436/9026) had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 55/9026 (0.61%) COVID-19 related hospitalisations/deaths were observed (34/5704 [0.60%] treated with nirmatrelvir/ritonavir and 21/3322 [0.63%] with sotrovimab). After adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, we observed no significant difference in outcome risk between nirmatrelvir/ritonavir and sotrovimab users (HR = 0.89, 95% CI: 0.48-1.63; P = 0.698). Results from propensity score weighted model also showed non-significant difference between treatment groups (HR = 0.82, 95% CI: 0.45-1.52; P = 0.535). The exploratory analysis comparing nirmatrelvir/ritonavir users with 1041 molnupiravir users (13/1041 [1.25%] COVID-19 related hospitalisations/deaths) showed an association in favour of nirmatrelvir/ritonavir (HR = 0.45, 95% CI: 0.22-0.94; P = 0.033).

Interpretation: In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received nirmatrelvir/ritonavir and sotrovimab between February and November 2022, when Omicron subvariants BA.2, BA.5, or BQ.1 were dominant.

Funding: UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.

Keywords: COVID-19; Comparative effectiveness; Paxlovid; Real-world data; Sotrovimab.

Abstract

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