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

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.

Rotavirus (RV) is the most common cause of acute gastroenteritis and a major cause of death in young children worldwide. Vaccination has been instrumental in reducing the impact of RV disease. Real-world evidence suggests an increased risk of intussusception (an infrequent type of bowel obstruction) in infants following RV vaccination. We reviewed IS cases reported spontaneously worldwide in children following a two-dose vaccination with the human RV vaccine (Rotarix, GlaxoSmithKline [GSK]) since its launch in 2004. We observed that (1) IS occurred more frequently 7 days after the first dose and, to a lesser extent, after the second dose; (2) boys were more frequently affected than girls (56.3%); (3) of 862 confirmed reported cases, 557 required hospitalisation; and (4) surgical intervention was required for 294 of 557 hospitalised cases. We used statistical analysis to assess whether the number of cases observed would be higher or lower than the natural occurrence of IS (irrespective of vaccination). These results were in line with the known RV vaccine safety profile. It is important to constantly monitor the real-world safety profile of RV vaccines in the postmarketing setting. Since the outcomes of early management of IS are favourable compared with delayed management, healthcare professionals should inform parents to seek immediate medical advice if they observe unusual behaviour in their vaccinated child. In conclusion, our analyses on data of a large patient pool for this rare event reinforce the favourable safety profile of human RV vaccine and the benefits of vaccination in young children.

The adjuvanted recombinant zoster vaccine co-administered with the 13-valent pneumococcal conjugate vaccine in adults aged ≥50 years: A randomized trial.

BACKGROUND: Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Adults at increased risk of HZ (due to immunocompromising conditions or older age) are also at risk of pneumococcal disease, both of which are preventable by vaccination. We evaluated simultaneous versus sequential administration of the adjuvanted recombinant zoster vaccine (RZV) and the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. METHODS: In this phase IIIB multinational trial (NCT03439657), participants were randomized 1:1 to receive either the first RZV dose and PCV13 simultaneously followed by the second RZV dose two months later (Co-Ad, N = 449), or at two-month intervals, PCV13, the first RZV dose, and the second RZV dose sequentially (Control, N = 463). Objectives were to demonstrate that immune responses to both vaccines are non-inferior when co-administered compared to sequential administration and to evaluate the safety of their co-administration. RESULTS: The RZV vaccine response rate (VRR) in the Co-Ad group was 99.1% (95% confidence interval [CI]: 97.6-99.7), meeting the VRR success criterion. Non-inferiority criteria for the Co-Ad versus Control group were also met for anti-glycoprotein E antibodies (adjusted geometric mean concentration Control/Co-Ad ratio 1.07 [95%CI: 0.99-1.16]) and all PCV13 serotypes (adjusted antibody geometric mean titer Control/Co-Ad ratios 1.02 [95%CI: 0.86-1.22] to 1.36 [95%CI: 1.07-1.73]). Upon co-administration, the frequency of solicited local adverse events was consistent with the known safety profile of each individual vaccine, whereas solicited general adverse events were within the same range as for RZV alone. CONCLUSIONS: RZV co-administered with PCV13 had an acceptable safety profile. Humoral immune responses to both vaccines were non-inferior when co-administered compared to sequential administration. These results suggest that adults may benefit from receiving RZV and a PCV at the same healthcare visit.