(B-308) Safety Monitoring of Mpox Vaccines in Adults Aged 18–64 Years during the 2022 Mpox Outbreak in the U.S.

Background: Two orthopoxvirus vaccines (JYNNEOS and ACAM2000) were used to prevent mpox in the United States (U.S.) during the 2022 clade II outbreak, with a preferential recommendation for JYNNEOS. Large cohort-based studies on the safety of JYNNEOS have not been published to date.

Objectives: As part of the Biologics Effectiveness and Safety Initiative, the U.S. Food and Drug Administration assessed the safety of JYNNEOS among U.S. adults aged 18–64 years during the 2022 mpox outbreak.

Methods: Data from three U.S. commercial claims databases (Carelon Research, CVS Health, Optum), supplemented with data from available Immunization Information Systems (IIS), were used. Our study population included persons aged 18–64 years who received at least one JYNNEOS dose. The study period was May 2022–June/July 2023. We monitored JYNNEOS uptake and occurrence of 11 potential incident adverse events (AEs) in outcome-specific risk windows following vaccination. Observed rates of each AE following any JYNNEOS dose and corresponding exact 95% confidence intervals (CIs) were estimated. We also estimated the age-sex standardized expected rates of each AE and 95% CIs using 2019 background rates (if available). We aggregated all statistics across the three databases to protect privacy. We reviewed medical claims profiles prior to myocarditis/pericarditis diagnoses to assess for pre-existing conditions.

Results: There were 152,001 JYNNEOS doses administered to 92,340 persons. There were 15 or fewer cases of each AE. Historical background rates from 2019 were available for 9 of the 11 AEs. Point estimates of observed rates were lower than expected rates in all instances except two (anaphylaxis and myocarditis/pericarditis). The anaphylaxis rate (based on < 10 unique cases) in the 0–1 days following vaccination was extremely imprecise due to small case counts (123.1 (95% CI: 3.1, 685.8) per 100,000 person-years compared to the expected rate of 11.8 (95% CI: 5.4, 19.5) per 100,000 person-years). The myocarditis/pericarditis rate in the 1–42 days following vaccination (based on 10 unique cases) was 90.2 (95% CI: 43.3, 165.9) per 100,000 person-years compared to the expected rate of 39.7 (95% CI: 25.7, 50.6) per 100,000 person-years. Based on the claims profile review (N = 8 cases available), all eight persons had at least one risk factor for myocarditis/pericarditis present prior to vaccination, including recent coronary artery bypass grafting, alcohol abuse, atrial fibrillation, HIV, or cardiomyopathy.

Conclusions: This study used real-world data, including claims supplemented with IIS data, to monitor the safety of JYNNEOS in U.S. adults aged 18–64 years during the 2022 mpox outbreak. No significant safety concerns were identified.