BACKGROUND: Live, oral, human rotavirus vaccine(HRV) was launched in the US in August 2008. Pre-li-censure studies did not suggest an increased risk for intussusception (IS) or other outcomes following HRV vaccination. Post-marketing safety studies indicate a transient increased incidence of IS.
OBJECTIVES: This retrospective and prospective observational study (NCT00875641) compares the incidence of IS, acute lower respiratory tract infection hospitalization (LRTI), Kawasaki disease (KD), convulsions, and mortality in infants receiving HRV to infants receiving inactivated poliovirus vaccine (IPV)in concurrent (cIPV) and recent historical (hIPV)cohorts.
METHODS: The study population was identified in 2health insurance claims databases from August 2008to June 2013 (HRV and cIPV infants) and January2004 to July 2008 (hIPV infants). IPV infants were frequency-matched to HRV infants in a 3:1 ratio by age, sex, and calendar quarter/year of first vaccination. All outcomes were identified in the claims in a 0–59day risk window after the first 2 vaccine doses. IS, KD, and convulsions were confirmed with medical re-cord review. Additional deaths were identified via a National Death Index search. Outcome incidence rates(IR) in the HRV cohort were compared to the IPV co-horts with covariate adjusted incidence rate ratios(IRR) and corresponding 95% confidence intervals(CI) from Poisson regression models. A post-hoc self-controlled case series (SCCS) analysis compared IRs of convulsions within each cohort in a 0–7 day risk window to a 15–30 day self-control window. An absence of increased outcome risk was concluded ifthe 95% CI of the IRR contained 1, or if the upper limit was below 2.5.
RESULTS: A total of 57,931 HRV infants were matched to 173,384 cIPV and 159,344 hIPV infants. Increased incidence of IS, LRTI, or mortality was not observed in the HRV cohort versus the IPV cohorts, with IRRsranging from 0.36 to 2.25 across doses and 95% CIsfrom 0.05 (lower bound) to 10.05 (upper bound). NoKD cases were observed in the HRV cohort. Increased incidence of convulsions was observed afterHRV Dose 1 (cIPV IRR: 2.07, 95% CI: 1.27–3.38;hIPV IRR: 2.05, 95% CI: 1.24–3.38). The IRR afterHRV Dose 1 in the SCCS analysis was not statistically significant (2.40, 95% CI: 0.73–7.86).The wide 95% CI is indicative of the small numberof events.
CONCLUSIONS: Infants vaccinated with HRV did not show evidence of increased risk for any of the 5outcomes in the 0–59 days following vaccination, compared to the 2 IPV control cohorts.
