Comparing Safety and Effectiveness of Pfizer BA.4-5 and Sanofi bivalent COVID-19 Vaccines Used in the Spring 2023 Booster Programme in England: a Target Trial Emulation Study Using the OpenSAFELY Platform

Monday, August 26, 2024

1:30 PM – 1:45 PM CEST

Location: Conv Hall I C

Presenting Author(s)

William Hulme, MSc PhD (he/him/his)

Statistical Epidemiologist
Bennett Institute of Applied Data Science, Nuffield Dept of Primary Care Health Sciences, University of Oxford
Oxford, United Kingdom

Slides

Co-Author(s)

CA

Colm Andrews

Bennett Institute of Applied Data Science, Nuffield Dept of Primary Care Health Sciences, University of Oxford, United Kingdom
EP

Em Prestige

London School of Hygiene and Tropical Medicine, United Kingdom
EP

Edward Parker

London School of Hygiene and Tropical Medicine, United Kingdom
VW

Venexia M. Walker, PhD

Research Fellow in Medical Statistics and Health Data Science
University of Bristol
Bristol, United Kingdom
CW

Christopher Wood

Clinical Informatician
Bennett Institute of Applied Data Science, Nuffield Dept of Primary Care Health Sciences, University of Oxford, United Kingdom
BS

Becky Smith

Bennett Institute of Applied Data Science, Nuffield Dept of Primary Care Health Sciences, University of Oxford, United Kingdom
AS

Andrea Schaffer

Bennett Institute of Applied Data Science, Nuffield Dept of Primary Care Health Sciences, University of Oxford, United Kingdom
AW

Alex Walker

Bennett Institute of Applied Data Science, Nuffield Dept of Primary Care Health Sciences, University of Oxford, United Kingdom
HC

Helen Curtis

Bennett Institute of Applied Data Science, Nuffield Dept of Primary Care Health Sciences, University of Oxford, United Kingdom
BM

Brian MacKenna

Bennett Institute of Applied Data Science, Nuffield Dept of Primary Care Health Sciences, University of Oxford, United Kingdom
AM

Amir Mehrkar

University of Oxford, United Kingdom
BG

Ben Goldacre

University of Oxford, United Kingdom
Miguel A. Hernán

CAUSALab, Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, United States
Jonathan Sterne, MSc PhD (he/him/his)

Professor of Medical Statistics and Epidemiology
University of Bristol
Bristol, United Kingdom

Background: The spring 2023 COVID-19 booster vaccination programme in England used both Pfizer BA.4/BA.5 and Sanofi vaccines. All people aged 75 years or over, and people considered clinically vulnerable were eligible. There is limited evidence on the comparative safety and effectiveness of these these vaccines in trials and observational data.

Objectives: To compare safety and effectiveness between the Pfizer BA.4/BA.5 and Sanofi vaccines during the spring 2023 booster programme in England.

Methods: With the approval of NHS England, we used the OpenSAFELY-TPP database to collect information on people receiving a COVID-19 booster vaccine between between 1 April and 30 June 2023 in England. We studied two cohorts separately: those aged 75 or over (75+); those aged 50 or over and clinically vulnerable (CV). In each cohort, vaccine recipients were matched on date of vaccination, COVID-19 vaccine history, age, and other characteristics. Effectiveness outcomes were COVID-19 hospital admission, COVID-19 critical care admission, and COVID-19 death up to 16 weeks after vaccination. Safety outcomes were Pericarditis and Myocarditis up to 4 weeks after vaccination. We report the cumulative incidence of each outcome, and compare safety and effectiveness using risk differences (RD), relative risks (RR), and incidence rate ratios (IRRs).

Results: After 1-1 matching, 492,642 people were included in the CV cohort, and 673,926 in the 75+ cohort, contributing a total 7,423,251 and 10,173,230 person-weeks of follow-up respectively. The incidence of COVID-19 hospital admission was higher for Sanofi than for Pfizer BA.4/BA.5. In the CV cohort, 16-week risks per 10,000 people were 22.3 (95% CI 20.4 to 24.3) for Pfizer BA.4/BA.5 and 26.4 (24.4 to 28.7) for Sanofi, with an IRR of 1.19 (95%CI 1.06 to 1.34). In the 75+ cohort, these were 17.5 (16.1 to 19.1) for Pfizer BA.4-5 and 20.4 (18.9 to 22.1) for Sanofi, with an IRR of 1.18 (1.05-1.32). These finding were similar across all pre-specified subgroups. More severe COVID-19 related outcomes (critical care admission and death), and safety outcomes at 4 weeks, were rare in both vaccines so we could not reliably estimate superiority of either vaccine.

Conclusions: This observational study comparing effectiveness of Pfizer BA.4/BA.5 and Sanofi vaccine during the spring 2023 programme in England in the two main eligible cohorts – people aged 75 and over and in clinically vulnerable people – found some evidence of superior effectiveness against COVID-19 hospital admission for Pfizer BA.4/BA.5 compared with Sanofi within 16 weeks after vaccination. Differences were largely observed during weeks 2 to 4 after vaccination only, suggesting that Pfizer BA.4/BA.5 offers earlier protection via more rapid immunogenicity, as seen in RCTs.