A Safety Profile Analysis of Adverse Events After Measles- Mumps-Rubella and Varicella Immunization Based on Italian Pharmacovigilance Network in Veneto Region

Introduction: Immunisation against measles, mumps, rubella and varicella can be achieved with two different strategies: the combination of measles-mumps-rubella (MMR) vaccine (available in Italy since the early 1990s) at the same time with the varicella vaccine (V) since 2005, or the use of the combined measles-mumps-rubellarubella-varicella vaccine (MMRV) available in the Veneto region since 2007. Several studies have compared the immunogenicity, reactogenicity and side effects of the two strategies since the introduction of MMRV [1-3]. There is evidence that shows a potential increased risk of febrile convulsions with the first dose of MMRV vaccine: several post-marketing surveillance studies have shown an approximately 2-fold increase for MMRV [4-5] Objective: To compare the safety profile of MMR + V and MMRV by analysing data from the Italian spontaneous reporting system in Veneto region. Methods: All reports coming from the Veneto Region related to MMRV or MMR+V vaccines and sent to the national pharmacovigilance database up to the end of March 2022 were included. Among each vaccine group the proportion of reporting AEFI and the proportion of serious events were compared. Adverse events were grouped according to the Medical Dictionary for Regulatory Activities (MedDRA). Results: A total of 5662 reports related to MMRV and 3848 reports related to MMR + V were retrieved and analysed. A high number of these reports was collected within an active surveillance project on the safety profile of the first doses of both schedules. Most of the reports referred to infants (1 month to < 2 years 94.5% of total reports for MMRV versus 99% for MMR + V) and children (2-11 years 5.3% for MMRV versus 0.6% for MMR + V). Proportion of serious reports was 19.7% (1116/5662) for MMRV and 9.7% (375/3848) for MMR + V. Preferred terms (PT) most frequently reported were pyrexia (45.5% for MMRV versus 29,5% for MMR + V), morbilliform rash (10.3% vs 12%) and post-vaccinal irritability (7.8% vs 14%). Among serious events the most frequent was hyperpyrexia (9% vs 3.7%, on the total PT reported). Febrile convulsions were 157 for MMRV (2.8%) and 43 for MMR + V (1.1%) 140 febrile convulsions were reported in 1% of MMRV reports and 0.4% of MMR+V. Reports of thrombocytopenia were 15 associated to MMRV (0.1%) and 1 to MMR+V (0.01%). Conclusion: Data from spontaneous reporting show some differences in the risk profile of MMRV in comparison to MMR + V, in line with data from the literature