Review of Over 15 Years Postmarketing Safety Surveillance Spontaneous Data for the Human Rotavirus Vaccine (Rotarix) on Intussusception

Abstract

Introduction: Rotavirus (RV) is the most common cause of acute gastroenteritis in children <5 years of age worldwide, and vaccination reduces the disease burden. Evidence from postmarketing surveillance studies suggested an increased risk of intussusception (IS) in infants post-RV vaccination. An overall positive benefit-risk balance for the human RV vaccine (HRV) Rotarix (GlaxoSmithKline [GSK], Belgium) has been established and recent findings indicate an indirect effect of reduced IS over the long term.

Objective: The aim of this study was to discuss spontaneous data from the GSK worldwide safety database on IS post-Rotarix administration.

Methods: The database was reviewed for all spontaneous IS cases from 2004 to 2020. Additionally, an observed versus expected (O/E) analysis was done for adverse events attributed to IS. Data were reviewed as overall worldwide and stratified by region (Europe/USA/Japan) and dose.

Results: A male predominance of IS patients was observed, consistent with earlier reports. The most frequently reported events in confirmed IS cases (Brighton Collaboration Working Group [BCWG] level 1) with time to onset ≤ 30 days post-vaccination were vomiting (55.8%), haematochezia (47.2%), and crying (21.1%). The observations from the IS spontaneous cases review and results of the O/E analysis are consistent with the known IS safety profile of RV vaccines: a transient increased incidence of IS post-vaccination (primarily in Europe/Japan/worldwide), mostly within 7 days postdose 1.

Conclusion: Since the outcomes of early IS management are favourable over delayed management, healthcare professionals should inform parents about the importance of seeking immediate medical advice in case of unusual behaviour of the vaccinated infant. GSK continues to monitor the IS risk post-Rotarix administration through routine pharmacovigilance activities.

Fig. 1

Overview of the time to onset of intussusception, reported hospitalisation, duration between intussusception onset and treatment start, and required surgery with or without resection for all spontaneous intussusception cases. *Duration of hospitalisation for these cases is detailed in electronic supplementary material 2. BCWG Brighton Collaboration Working Group, IS intussusception, TTO time to onset

Fig. 2

Distribution of the time to onset of intussusception after administration of the rotavirus vaccine for the confirmed cases with a time to onset of ≤ 30 days (N = 634). Cases with a reported time to onset of ‘less than one a day’ or ‘same day’ are represented as 0 days from the last dose; cases with a reported time to onset of ‘2–3 days’ are represented as 2 days from the last dose; cases with a reported time to onset of ‘< 7 days’ are represented as 6 days from the last dose; and cases with a reported TTO of ‘1 week’ are represented as 7 days from the last dose. IS intussusception, N total number of confirmed cases, RV rotavirus vaccine