Safety study of live, oral human rotavirus vaccine: A cohort study in United States health insurance plans

Veena Hoffman,Remon Abu-Elyazeed,Cheryl Enger,Daina B Esposito,Michael C Doherty,Scott C Quinlan,Kathleen Skerry,Crystal N Holick,Peter Basile,Leonard R Friedland,Nicolas Praet,Stéphanie Wéry,Corinne Willame,David D Dore,Dominique Rosillon

doi:10.1080/21645515.2018.1450123

Abstract

ABSTRACTAs part of a regulatory commitment for post-licensure safety monitoring of live, oral human rotavirus vaccine (RV1), this study compared the incidence rates (IR) of intussusception, acute lower respiratory tract infection (LRTI) hospitalization, Kawasaki disease, convulsion, and mortality in RV1 recipients versus inactivated poliovirus vaccine (IPV) recipients in concurrent (cIPV) and recent historical (hIPV) comparison cohorts. Vaccine recipients were identified in 2 claims databases from August 2008 – June 2013 (RV1 and cIPV) and January 2004 – July 2008 (hIPV). Outcomes were identified in the 0–59 days following the first 2 vaccine doses. Intussusception, Kawasaki disease, and convulsion were confirmed via medical record review. Outcome IRs were estimated. Incidence rate ratios (IRRs) were obtained from Poisson regression models. A post-hoc self-controlled case series (SCCS) analysis compared convulsion IRs in a 0–7 day post-vaccination period to a 15–30 day post-vaccination period. We identified 57,931 RV1, 173,384 cIPV, and 159,344 hIPV recipients. No increased risks for intussusception, LRTI, Kawasaki disease, or mortality were observed. The convulsion IRRs were elevated following RV1 Dose 1 (cIPV: 2.07, 95% confidence interval [CI]: 1.27 – 3.38; hIPV: 2.05, 95% CI: 1.24 – 3.38), a finding which is inconclusive as it was observed in only one of the claims databases. The IRR following RV1 Dose 1 in the SCCS analysis lacked precision (2.40, 95% CI: 0.73 – 7.86). No increased convulsion risk was observed following RV1 Dose 2. Overall, this study supports the favorable safety profile of RV1. Continued monitoring for safety signals through routine surveillance is needed to ensure vaccine safety.

Highlights

Rotavirus is the most common cause of acute or severe gastroenteritis in children younger than 5 years of age
Among RV1 and inactivated poliovirus vaccine (IPV) recipients, 67 intussusception, 1,966 acute lower respiratory tract infection (LRTI), 24 Kawasaki disease, and 593 convulsion events were identified in the claims data, and 69 mortality events were identified in the claims data or National Death Index (NDI)
This study is the first to assess the risk of intussusception and other safety outcomes over a 60-day risk period following each dose of RV1 administration

Summary

Introduction

Rotavirus is the most common cause of acute or severe gastroenteritis in children younger than 5 years of age. In 2008, the virus was associated with an estimated 453,000 deaths worldwide each year.[1] As of 2009, rotavirus caused an estimated 3 million cases of diarrhea among children in the United States (US) each year with medical attention sought for 500,000 children and resulting in 60,000–70,000 hospitalizations.[2]. Two rotavirus vaccines are currently licensed by the US Food and Drug Administration. Human-bovine reassortant rotavirus vaccine (RV5, RotaTeq, Merck and Co., Inc., USA), was licensed in the US in 2006 and is administered in 3 doses at 2, 4, and 6 months of age. Oral human rotavirus vaccine (RV1, Rotarix, GSK, Belgium) was licensed in the US in 2008 and is administered in 2 doses at 2 and 4 months of age.

Methods

Results

Conclusion