Real-World Safety of Concurrent Measles–Mumps–Rubella and Varicella Vaccination in Korean Infants: A Multicenter Self-Controlled Case Series Study

Background: Measles, mumps, rubella (MMR) and varicella vaccines are often co-administered to optimize coverage, yet safety concerns regarding febrile convulsions persist. In South Korea, MMR and varicella vaccines are administered as separate injections during a single visit (MMR + V). This study evaluated the real-world safety of concurrent MMR + V vaccination, focusing on the domestically implemented MAV/06 and Oka-derived strains. Methods: We conducted a multicenter self-controlled case series (SCCS) study of children aged 12–23 months who received MMR + V and hepatitis A vaccine (HAV) between 2015 and 2024. Using electronic health records, we identified predefined adverse events (AEs), including fever and healthcare visits. Adjusted relative risks (aRRs) were estimated using conditional Poisson regression. Results: Among 3035 children (52.3% male; median age, 12 months), 71.7% received the MAV/06 varicella strain. A distinct peak in AEs occurred 7–13 days after MMR + V administration, with fever showing the greatest increase (aRR, 4.27; 95% CI, 2.76–6.60). The risks of total sick visits (aRR, 2.15; 95% CI, 1.70–2.71) and acute care visits (aRR, 2.13; 95% CI, 1.46–3.10) were similarly confined to this interval and returned to baseline thereafter. Febrile convulsions were uncommon (aRR, 5.37; 95% CI, 1.20–24.01). No excess risks were observed during the HAV or overlap periods, and no synergistic effects of intensive multi-vaccine administration were detected. Conclusions: Concurrent administration of MMR and varicella vaccines in Korean infants—predominantly using the MAV/06 strain—was associated only with expected, transient increases in fever during days 7–13 postvaccination. No serious or sustained safety signals were identified, supporting the continued use of Korea’s separate-injection MMR + V strategy.