Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform

{ 'institution': [{'name': 'medRxiv'}], 'indexed': {'date-parts': [[2023, 1, 24]], 'date-time': '2023-01-24T05:56:44Z', 'timestamp': 1674539804597}, 'posted': {'date-parts': [[2023, 1, 22]]}, 'group-title': 'Epidemiology', 'reference-count': 0, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2023, 1, 22]]}, 'abstract': '<jats:p>Objective: To compare the effectiveness of Paxlovid vs. sotrovimab and molnupiravir ' 'in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients. ' 'Design: With the approval of NHS England, we conducted a real-world cohort study using the ' 'OpenSAFELY-TPP platform. Setting: 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 COVID-19 infection and therapeutics, ' 'hospital admission, and death within the OpenSAFELY-TPP platform, covering a period where ' 'both Paxlovid and sotrovimab were first-line treatment options in community settings. ' 'Participants: Non-hospitalised adult COVID-19 patients at high risk of severe outcomes ' 'treated with Paxlovid, sotrovimab or molnupiravir between February 11, 2022 and October 1, ' '2022. Interventions: Paxlovid, sotrovimab or molnupiravir administered in the community by ' 'COVID-19 Medicine Delivery Units. Main outcome measure: COVID-19 related hospitalisation or ' 'COVID-19 related death within 28 days after treatment initiation. Results: A total of 7683 ' 'eligible patients treated with Paxlovid (n=4836) and sotrovimab (n=2847) were included in the ' 'main analysis. The mean age was 54.3 (SD=14.9) years; 64% were female, 93% White and 93% had ' 'three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 52 (0.68%) ' 'COVID-19 related hospitalisations/deaths were observed (33 (0.68%) treated with Paxlovid and ' '19 (0.67%) with sotrovimab). Cox proportional hazards model stratified by region showed that ' 'after adjusting for demographics, high-risk cohort categories, vaccination status, calendar ' 'time, body mass index and other comorbidities, treatment with Paxlovid was associated with a ' 'similar risk of outcome event as treatment with sotrovimab (HR=1.14, 95% CI: 0.62 to 2.08; ' 'P=0.673). Results from propensity score weighted Cox model also showed comparable risks in ' 'these two treatment groups (HR=0.88, 95% CI: 0.45 to 1.71; P=0.700). An exploratory analysis ' 'comparing Paxlovid users with 802 molnupiravir users (11 (1.37%) COVID-19 related ' 'hospitalisations/deaths) showed some evidence in favour of Paxlovid but with variation in the ' 'effect estimates between models (HR ranging from 0.26 to 0.61). Conclusion: 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 ' 'Paxlovid and sotrovimab between February and October 2022, when different subvariants of ' 'Omicron were dominant.</jats:p>', 'DOI': '10.1101/2023.01.20.23284849', 'type': 'posted-content', 'created': {'date-parts': [[2023, 1, 23]], 'date-time': '2023-01-23T06:05:17Z', 'timestamp': 1674453917000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe ' 'COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY ' 'platform', 'prefix': '10.1101', 'author': [ {'given': 'Bang', 'family': 'Zheng', 'sequence': 'first', 'affiliation': []}, {'given': 'John', 'family': 'Tazare', 'sequence': 'additional', 'affiliation': []}, {'given': 'Linda', 'family': 'Nab', 'sequence': 'additional', 'affiliation': []}, {'given': 'Amir', 'family': 'Mehrkar', 'sequence': 'additional', 'affiliation': []}, {'given': 'Brian', 'family': 'MacKenna', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-5127-4728', 'authenticated-orcid': False, 'given': 'Ben', 'family': 'Goldacre', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ian J', 'family': 'Douglas', 'sequence': 'additional', 'affiliation': []}, {'given': 'Laurie', 'family': 'Tomlinson', 'sequence': 'additional', 'affiliation': []}, {'name': 'The OpenSAFELY Collaborative', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'container-title': [], 'original-title': [], 'link': [ { 'URL': 'https://syndication.highwire.org/content/doi/10.1101/2023.01.20.23284849', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 1, 23]], 'date-time': '2023-01-23T06:05:18Z', 'timestamp': 1674453918000}, 'score': 1, 'resource': {'primary': {'URL': 'http://medrxiv.org/lookup/doi/10.1101/2023.01.20.23284849'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 1, 22]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.1101/2023.01.20.23284849', 'relation': {}, 'published': {'date-parts': [[2023, 1, 22]]}, 'subtype': 'preprint'}