Mary Ellen Schneider, New York Bureau, contributed to this report.
ATLANTA — The rotavirus vaccine RotaTeq is not associated with an increased risk of intussusception in infants during either the 1- to 7-day period after vaccination or the 1- to 21-day period, according to data from the U.S. Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink.
However, ongoing monitoring will be needed to fully assess the safety profile of the human-bovine reassortant rotavirus vaccine, researchers said at the June meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention. The findings were reported in part in the June issue of Pediatrics (2008;121:1206-12).
The safety of the vaccine has been under scrutiny because a previous rotavirus vaccine, RotaShield, was associated with intussusception. It was pulled from the market in 1999 after reports from the U.S. Vaccine Adverse Event Reporting System (VAERS) found it had a 37-fold elevated risk for intussusception in the 3–7 days after the first dose.
Dr. Penina Haber of the Immunization Safety Office at the CDC presented the VAERS data for RotaTeq, including sensitivity analysis to compensate for incomplete reporting to the passive system and to estimate the number of doses administered.
Between RotaTeq's licensure on Feb. 1, 2006, through March 31, 2008, VAERS received 2,600 reports of adverse events associated with the vaccine, of which 26% were serious. The most frequently reported events were diarrhea and vomiting, and 44% of all events involved the first of the three vaccine doses. During that time period, Merck & Co. distributed a total of 14,274,551 doses of RotaTeq.
The reports included 267 confirmed cases of intussusception, of which 91 were reported 1–21 days after receipt of the vaccine and 48 of those 91 (53%) were reported within 1–7 days. There was one death 16 days after receipt of dose two, said Dr. Haber.
In sensitivity analyses, it was estimated that if VAERS reporting were 100% complete and 100% of the vaccine had been administered, the observed rates of intussusception after any dose were lower than expected for both the 1- to 21-day period post vaccination (92 vs. 242) and the 1- to 7-day period (49 vs. 81). But if reporting and administration were at 50%, it seemed there would be a statistically significant association between administration and intussusception for the 1- to 7-day period, with relative risks of 2.25 after any dose and 4.14 after dose one.
However, VAERS is not designed to test hypotheses, said Dr. Haber. That is done by Vaccine Safety Datalink (VSD), a system designed to test hypotheses generated by VAERS by linking vaccination data from several HMOs to patients' medical outcomes.
Dr. James Baggs, also with the CDC's Immunization Safety Office, presented the VSD data. The system's Rapid Cycle Analysis method is an alternative to postlicensure vaccine safety study methods that typically take years to complete, and can identify prespecified vaccine adverse events in “near real time.”
In seven of eight VSD sites, children who received any dose of RotaTeq from age 4 weeks to 48 weeks were identified and compared with those aged 4–52 weeks enrolled in VSD during 1991–2004. Of 205,179 doses administered, 5 observed intussusception cases were identified from the computerized data, compared with 6.65 that would have been expected from the age-adjusted 1991–2004 background rate. After the 77,162 first doses, there were 2 intussusception reports, compared with an expected rate of 1.39. That relative risk, of 1.44, did not reach the specified threshold required to generate a safety signal.
None of the five cases occurred within 1–7 days of vaccine receipt, and subsequent medical record validation results showed that two of the five cases met the case criteria for intussusception, with neither occurring following dose one. Taken together, data from VAERS, VSD, and the prelicensure trial suggest the risk for intussusception after a first dose of RotaTeq is not greater than one to two per 50,000 first doses administered, Dr. Baggs said.
The researchers are also starting a Rapid Cycle Analysis of GlaxoSmithKline's Rotarix.