(262) Signal detection, refinement, & evaluation of cerebral venous sinus thrombosis following Spikevax administration in a US active surveillance system
Sr. Scientist Aetion, Inc. Washington, United States
Background: Moderna, Inc. is conducting active surveillance to identify and evaluate the potential risk of adverse events of special interest after administration of the Spikevax vaccine. Cerebral venous sinus thrombosis (CVST) is one of these events.
Objectives: To evaluate the risk of CVST following receipt of Spikevax among adults in a US administrative claims database.
Methods: In an ongoing surveillance study of pre-specified AESI using medical and pharmacy claims data from HealthVerity, incidence rates (IR) following mRNA-1273 vaccination were estimated per 100,000 person-years (PY) and compared to historical background rates. Where criteria were met, self-controlled risk interval (SCRI) analyses were conducted. For CVST, event rate ratios (ERR) and corresponding 95% CIs were calculated comparing rates in the 28-day risk and 42-day control periods. Analyses were stratified by age, sex, age by sex, dose and immunocompromise. Sensitivity analyses explored the impact of open vs. closed claims, COVID-19 exclusions, and varying risk windows. To address potential misclassification, an alternate case algorithm requiring evidence of diagnostic imaging in addition to ICD-10 diagnosis codes was applied.
Results: Among 23,688,817 total Spikevax vaccinees, prespecified criteria for SCRI were met. No increase was observed in the overall dose-agnostic SCRI including 133 events (ERR 1.16, 95%CI 0.82-1.62), however an increased rate was observed in those ≥75 years of age (30 events, ERR= 2.33, 95% CI 1.05 - 5.19). Additional SCRI sensitivity analyses using more discrete risk windows led to greater ERRs for those ≥75 years after dose 2 in days 8-14 (5 risk window and 9 control window events, ERR 6.00, 95%CI 1.74-15.06), however an increased post-dose 2 risk was not observable in this age group when analyses limited to closed claims (1 risk window event) or required evidence of diagnostic imaging (2 risk window and 1 control window events).
Conclusions: An elevated risk window rate of CVST was observed among adults ≥75 years, however results from the sensitivity analysis indicate likely misclassification of the outcome.
