Intussusception risk after RotaTeq vaccination: evaluation from worldwide spontaneous reporting data using a self-controlled case series approach.

The increased risk of intussusception after vaccination with the rhesus-human reassortant rotavirus vaccine Rotashield led to its withdrawal in 2005. We assess the risk of intussusception following the pentavalent rotavirus vaccine (RV5) on the basis of worldwide reports to the manufacturer up to May 2014, using a self-controlled case series. The method had to be modified to account for the under-reporting, a specific feature of pharmacovigilance spontaneous reports. The risk of intussusception occurring in either of the 0- to 2-day, 3- to 7-day or 8- to 14-day risk periods, was compared to the risk in the 15- to 30-day period. A total of 502 cases occurring 0-30 days after a vaccine dose were studied, including 188 cases after the first dose, 190 cases after the second dose, and 124 cases after the third dose. The incidence risk ratio relative to the control period was highest for the 3- to 7-day period and equal to 3.45 (95% CI 1.84-6.55), 1.63 (0.86-3.13) and 1.73 (0.86-3.51) after the first, second and third dose, respectively. Rotavirus vaccination with RV5 increases the risk of intussusception 3-7 days following vaccination, mainly after the first dose and marginally after the second and third doses. The risk is small and restricted to a short time window. It does not outweigh the benefit of the vaccination, but parents of vaccinated infants should be informed in order to react appropriately to the first symptoms. With appropriate assumptions about the reporting rate, spontaneous reports of adverse events after vaccination can be studied to evaluate vaccine safety.