Near real-time surveillance and tree-based data mining to assess the safety of respiratory syncytial virus vaccines in older adults in the vaccine safety datalink.

BACKGROUND: Two respiratory syncytial virus (RSV) vaccines, Pfizer's Abrysvo and GSK's Arexvy, were licensed in 2023 in the U.S. However, population-based assessments of their safety in adults ≥60 years have not been widely published. We provide results from two complementary investigations of vaccinated adults in the Vaccine Safety Datalink (VSD). METHODS: The rapid cycle analysis (RCA) used a sequential cohort design and biweekly analyses of near real-time data to compare the incidence of 12 pre-specified outcomes in two post-vaccination risk intervals (1-21, 1-42 days) with the incidence in comparison intervals. The surveillance period was August 1, 2023, through September 28, 2024; nine of 13 VSD sites participated. Statistically significant signals were investigated by medical record review with re-analysis of confirmed outcomes. The self-controlled tree-based data mining analysis was designed to identify temporal clustering of ICD-10 diagnosis codes in the inpatient or emergency department settings 1-56 days post-vaccination, without pre-specifying outcomes or risk intervals. The study period was July 1, 2023, through December 31, 2023; 10 sites participated. RESULTS: The RCA analysis included 436,823 persons who received an RSV vaccine. No statistical signal was identified for 11 of 12 adverse events. A signal was detected for immune thrombocytopenic purpura following Arexvy, but re-analysis following medical record review did not confirm an association. The tree-based data mining analysis included 248,056 vaccinees, identified 53,734 counts of 3429 diagnosis codes, and identified no statistically significant clusters for either vaccine. CONCLUSIONS: These post-licensure safety assessments provide evidence supporting the safety of RSV vaccines in older adults. As more data accrue, additional monitoring is warranted for rare adverse events.