Evaluation of the safety profile of rotavirus vaccines: a pharmacovigilance analysis on American and European data

Alessandro Ceschi,Domenico Motola,Alberto Vaccheri,Giulia Bonaldo,Roberta Noseda

doi:10.1038/s41598-020-70653-3

Alessandro Ceschi, Domenico Motola + Show 3 more

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https://doi.org/10.1038/s41598-020-70653-3

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Abstract

Rotaviruses (RVs) are the most common cause of severe diarrheal disease. To date two rotavirus oral vaccines are licensed: Rotarix and Rotateq. Our aim was to contribute to the post-marketing evaluation of these vaccines safety profile. We collected all RV vaccines-related reports of Adverse Events Following Immunization (AEFI) in US Vaccine Adverse Events Reporting System (VAERS) and VigiBase between January 2007 and December 2017. A disproportionality analysis using Reporting Odds Ratio (ROR) was performed. A total of 17,750 reports in VAERS and 6,358 in VigiBase were retrieved. In VAERS, 86.2% of the reports concerned RotaTeq, whereas in VigiBase 67.7% of them involved Rotarix. Across the databases, diarrhea (1,672 events in VAERS, 1,961 in VigiBase) and vomiting (1,746 in VAERS, 1,508 in VigiBase) were the most reported AEFIs. Noteworthy, the RV vaccines-intussusception pair showed a ROR greater than 20 in both databases. Some new potential safety signals emerged such as fontanelle bulging, hypotonic-hyporesponsive episode, livedo reticularis, and opisthotonus. Overall, our data show that most of the reported AEFIs are listed in the Summary of Product Characteristics (SPCs). However, there remains the need to investigate the potential safety signals arose from this analysis, in order to complete the description of the AEFIs.

Highlights

Rotaviruses (RVs) are the most common cause of severe diarrheal disease
In Vigibase the 67.7% was reported for Rotarix, 30.3% for RotaTeq and the 2.0% was without the brand name
Among vaccine-reaction pairs with a higher and statistically significant Reporting Odds Ratio (ROR) with RV vaccines vs. other vaccines, and a number of events greater than 25 (Table 3), we found several Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term (PT) related to the System Organ Class (SOC) “Gastrointestinal disorders” or specific for rotavirus such as: gastroenteritis rotavirus n = 96, ROR 82.49 [95% CI 63.12–107.80], rotavirus infection n = 199, ROR 81.45 [95% CI 68.64–96.65], rotavirus test positive n = 293, ROR 53.89 [95% CI 47.37–61.31] and the above-mentioned intussusception

Summary

Introduction

Rotaviruses (RVs) are the most common cause of severe diarrheal disease. To date two rotavirus oral vaccines are licensed: Rotarix and Rotateq. There remains the need to investigate the potential safety signals arose from this analysis, in order to complete the description of the AEFIs. Rotaviruses (RVs) are the most common cause of severe diarrheal disease in young children throughout the world[1]. After Rotashield withdrawal, great attention has been deserved for post-marketing safety studies focused on the risk of intussusception[14,15,16]. With this regards, in order to increase the quality of safety data on rotavirus vaccines and facilitate a global safety assessment, the WHO Global Advisory Committee on Vaccine Safety (GACVS) together with other expert groups, recommended a standardized post-marketing surveillance approach. Rationale is to enhance the quality of safety data available to allow a correct assessment of the safety of rotavirus vaccination worldwide[17]

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