Presented at the 43rd Annual Meeting of European Society for Pediatric Infectious Diseases (ESPID)
Background: ABRYSVO™ is a maternal vaccine to prevent infant RSV-associated lower respiratory tract illness. A rapid cycle analysis (RCA) is ongoing to conduct early detection of safety signals (EUPAS1000000115). Cumulative data through the second of five planned hypothesis tests are presented.
Objective: To rapidly monitor incidence proportions of 10 prespecified safety outcomes following ABRYSVO and comparator maternal vaccination using US administrative claims data.
Methods: Pregnancies vaccinated at 32-36 weeks' gestation with ABRYSVO (exposure) or influenza/Tdap/COVID-19 (comparator) were identified from September 2018-January 2023 (historical comparator) and September 2023-February 2024 (exposure, concurrent comparator). Outcome incidence was assessed using maximized Sequential Probability Ratio Tests, and included preterm birth, hypertensive disorders of pregnancy [HDP], stillbirth, premature labor without preterm delivery, premature rupture of membranes [PROM], preterm PROM; Guillain-Barré syndrome, small for gestational age, large for gestational age, and low birth weight. Potential confounding variables were maternal age, season, gestational age at vaccination, and evidence of high-risk for prematurity.
Results: Historical Comparison: 5,027 ABRYSVO-exposed and 143,459 comparator pregnancies were observed. Only PROM (crude incidence proportion [IP] 13.4% [95% CI: 12.4-14.3%] vs. 12.5% [12.4-12.7%]) and HDP (without secular trend adjustment) (crude IP 17.4% [16.4-18.5%] vs. 13.4% [13.2-13.6%]) met the criteria to reject the null hypothesis of no excess risk.
Concurrent Comparison: 5,028 ABRYSVO-exposed and 6,528 concurrent comparator pregnancies were observed. Only HDP (17.4% [16.4-18.5%] vs. 15.7% [14.8-16.6%]) met the criteria to reject the null hypothesis of no excess risk.
Monitoring is ongoing for all remaining outcomes that have not reached statistical stopping points.
Conclusions: Further investigation is needed to explore a potential increased risk of PROM and HDP following ABRYSVO exposure. RCAs, while allowing for rapid safety monitoring, have limited confounding control and therefore cannot demonstrate causality.
