Safety of Influenza Vaccine During the Vaccination Campaign 2021/2022 in Italy: A Self-Controlled Case Series Study

Abstract

Introduction. This study evaluated the safety of influenza vaccines in a large and representative population during the 2021/2022 campaign in Italy using a Self-Controlled Case Series (SCCS) design using regional health data registries. Methods. This multiregional study used healthcare data to assess pre-specified potential adverse outcomes after flu vaccination during the 2021/2022 season. Participants were individuals aged 6 months or older, vaccinated or not, admitted to emergency care or hospital for at least one of the incident outcomes of interest. Risk periods were specifically defined for each outcome and compared to reference periods. The Self-Controlled Case Series design modified for event-dependent exposures was used, estimating relative incidences and excess cases by age, sex, dose, and adjusting for calendar time. Results. No increased risks were observed for most of the study outcomes. An increased risk of thrombocytopenia (RI=1.90; 95% CI: 1.00–3.61) and optic nerve neuritis (RI=5.22; 95% CI: 1.31–20.79) was detected in individuals under 60 years. Sensitivity and ancillary analyses supported these findings. Conclusions. These findings confirm the overall safety of influenza vaccines during the 2021/2022 campaign, with no evidence of increased risk for most of the pre-specified adverse outcomes. The increased risks observed for thrombocytopenia and optic neuritis need further research.

Note:
Funding Information: This work was supported by the Italian Medicines Agency in the framework of the collaboration agreement 2022-2025 between Italian Medicines Agency and Italian National Institute of Health (FARV-AVPM n. 8).

Conflict of Interests: Authors, Stefania Spila-Alegiani, Marco Massari, Maria Cutillo, Francesca Menniti-Ippolito, Roberto Da Cas, Flavia Mayer, Giuseppe Marano, Valeria Belleudi, Antonio Addis, Valeria Desiderio, Nadia Mores, Sara Lopes, Maria Balducci, Lucian Ejlli, Stefania Del Zotto, Elena Clagnan, Sarah Samez, Cristina Zappetti, Paola Rossi, Ester Sapigni, Aurora Puccini, Marco Villa, Claudio Visigalli, Nicoletta Luxi, Cristina Morciano declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Gianluca Trifirò declares the following financial interests/personal relationships which may be considered as potential competing interests: he has served, over the last 3 years, on advisory boards/seminars funded by Sanofi, MSD, Eli Lilly, Sobi, Celgene, Daichii Sankyo, Novo Nordisk, Gilead, and Amgen on topics not related to content of this paper; he is also a scientific coordinator of the academic spin-off “INSPIRE srl,” which has received funding from several pharmaceutical companies (Kiowa Kirin, Shonogi, Shire, Novo Nordisk, and Daichii Sankyo) for conducting observational studies and additional consultancy services on topics not related to content of this paper. Additionally, he is currently a consultant for Viatris in a legal case concerning a topic not related to the content of this paper.

Ethical Approval: The study received the approval from the National ethics committee for clinical trials of public research bodies and other national public institutions (PRE BIO CE n.0036723, 23/09/2022).

Keywords: influenza vaccine, post-marketing drug surveillance, Self-Controlled Case Series, adverse drug events, routinely collected health data