Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study

Abstract

Since the influenza season 2018/19, the Italian Ministry of Health recommended a dose of cell-based quadrivalent vaccine (Flucelvax Tetra) for HCWs (healthcare workers), because this vaccine seemed more efficacious in the prevention of AH3N2 virus. Due to the lack of pre-registration data, the safety profile of this new vaccine must be investigated in post-marketing surveillance. The aim of our study is to evaluate, through a post-marketing active surveillance program developed during the 2019/20 influenza season, any Adverse Events Following Immunization (AEFIs) that happened in the 7 days after immunization with Flucelvax Tetra. The study was carried out in a sample of HCWs of Policlinico General University-Hospital (Apulia, South Italy). AEFIs were classified as ‘serious’ or ‘not serious’ according to the WHO (World Health Organization) guidelines; the WHO causality assessment algorithm was applied to classify serious AEFIs. A total of 741 HCWs were enrolled, and 430 AEFIs (reporting rate: 58.0 (95%CI: 54.4–61.6) × 100 enrolled) were recorded. Of these, 429 of 430 (99.8%; reporting rate: 57.8 (95%CI: 54.2–61.5) × 100 enrolled) were classified as not serious and one (0.2%; reporting rate: 0.13 (0.03–0.75) × 100 enrolled) was classified as serious. Local reactions were the adverse reaction reported most frequently (88%); regarding the serious AEFI, causality assessment excluded the causal link with the administration of the vaccine. All the AEFIs resolved without sequelae. Flucelvax Tetra showed a profile of high safety. Due to their characteristics of greater sensitivity than passive surveillance, active surveillance programs can be useful in defining the safety profiles of a given vaccine/drug in certain population subgroups.

Safety Profile of Recommended Vaccinations in Adolescents: Data from Surveillance of Adverse Events Following Immunization in Puglia (Italy), 2016–2020

“…The higher AEFI reporting rate in the Australian study may be explained by the greater attention of both Australian healthcare workers and patients to adverse event surveillance. Moreover, the great difference between the percentage of serious AEFIs in this study and ours may be explained not only by differences in the application of the WHO's causality assessment algorithm, but also by the tendency of Italian healthcare workers to primarily report serious adverse events, while non-serious ones often remain unnoticed [10,31].…”

“…Surveillance of adverse events following immunization (AEFIs) in the post-marketing life of new vaccines is therefore recommended by the World Health Organization (WHO) in order to better understand the safety profile and effectiveness of new drugs [9]. Indeed, post-marketing surveillance can lead to the detection of rare sanitary events that were not observed during pre-licensure studies through the revision of reporting rates and the analysis of the vaccine's safety profile in subgroups that were not represented in its pre-marketing life [10,11]. In order to grant a more ordinate approach to AEFIs surveillance, the WHO has recommended the application of a standardized causality assessment methodology instead of the earlier "emotional" approach, which would threaten to increase vaccine hesitancy [12].…”

Safety profile of MenB-FHBp vaccine among adolescents: data from surveillance of Adverse Events Following Immunization in Puglia (Italy), 2018–2020

“…This differences could be explained both considering hypotizing different applications of WHO Causality Assessment Algorithm (that is routinely applied in Italy only since 2013) and with the attitude of Apulian healthcare workers in missing the notification of nonserious AEFIs, already discussed in other surveys of our research group. 16 , 23 , 26 …”

“…15 In particular, postmarketing surveillance could help Public Health Authorities in detecting rare sanitary events not described in prelicensure studies, reviewing the reporting rate and having a picture of the vaccineʻs safety profile in subgroups not represented in its premarketing life. 16 , 17 These goals could be achieved using the standardized Causality Assessment methodology and avoiding the “emotional” approach on emerging AEFIs, that was in the past one of the most important causes of vaccine hesitancy. 18 …”

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy

“…The World Health Organization (WHO, Geneva, Switzerland) recommends surveillance of Adverse Events Following Immunization (AEFIs) during the post-marketing life of new vaccines as a mean to better understand the safety profile and effectiveness of new drugs [ 12 ]. Thanks to the revision of AEFIs’ reporting rates, post-marketing surveillance is indeed capable of detecting rare adverse events which pre-licensure studies could not observe, as well as studying the vaccine’s safety profile in subgroups that were not represented in pre-marketing trials [ 13 , 14 ]. The WHO has recommended the application of a standardized causality assessment methodology in order to grant a more ordinate approach to the surveillance of AEFIs, as well as to surpass the “emotional” approach, which may increase vaccine hesitancy while decreasing the quality of the surveillance data [ 15 ].…”