Safety of rotavirus vaccines
Data were presented by the manufacturers of RotaTeq® and Rotarix® rotavirus vaccines as well as by the CDC and the FDA. Data related mainly to the risk of intussusception, which had been identified as associated with a previous rotavirus vaccine. In addition, information was presented on Kawasaki disease following vaccination, for which there was limited, not statistically significant, evidence of an increased risk observed in a clinical trial for 1 of the 2 products.
With respect to Rotarix®, there was no evidence from any of the studies, which included over 30 000 vaccinees in trials and worldwide usage, with about 5 million doses distributed, that there was an excess incidence of intussusceptions. Those cases of intussusception that were reported did not show a pattern with regard to the time of onset following vaccination consistent with a causal relationship. The overall numbers of cases reported were much less than would have been expected based on applying rates for the normal incidence of intussusception to a population of the size vaccinated.
With respect to RotaTeq®, a large (>30 000) trial (the REST study) has been reported, and an observational cohort of 44 000 vaccinated children is planned. Most data relate to developed countries, especially in the post-marketing studies and spontaneous reporting. There is no evidence that the rate of intussusceptions is raised above background rates, and it is certainly much less than the rate previously observed with the vaccine that was withdrawn following an association with intussusception. The VAERS spontaneous reporting data also show a lower than expected rate of intussusception.
The REST study had 5 cases of Kawasaki disease in the vaccinated group compared with 1 in the placebo group. These cases were quite young, and it is not clear whether this rate in the vaccinated group is higher than expected. Detailed data on background incidence of Kawasaki disease are not well determined. The time to occurrence in vaccinated children does not show a pattern, but the number of reports is too low for a detailed assessment. The focus of the post-marketing surveillance has been largely targeted at intussusception, and there are few data on Kawasaki disease.
GACVS concluded that with regard to intussusception, the data, particularly those from developed countries, are reassuring. It was noted, however, that the present data relate mainly to vaccines administered to young children at the recommended age. It remains important that intussusception should be monitored in developing countries as rotavirus vaccines are introduced, especially because infants are likely to present for their first dose of vaccine at slightly older ages, on average, than is the case in developed countries.
With respect to the rare cases of Kawasaki disease that have been observed, while the evidence is at best a hint of a signal, the data do not yet permit a full evaluation of a possible risk. Kawasaki disease is not easy to diagnose in infancy and may not be reported if there is no suspicion that it could be caused by a vaccine. There is a need for careful assessment of Kawasaki disease in the existing data and to ensure that ongoing and future studies incorporate surveillance for Kawasaki disease following vaccination.1
1. In June 2007, the US Food and Drug Administration (FDA) (http://www.fda.gov/cber/products/rotateq.htm) approved a label change based on the reports of Kawasaki disease but did not make any changes to its indications for use of RotaTeq®, nor did the agency issue new or revised warnings or precautions. In its announcement of the label change, the FDA stated that cases reported to date were no more frequent those that could be expected to occur by coincidence and that health-care practitioners and parents should remain confident in using RotaTeq®. Likewise, the US Centers for Disease Control and Prevention did not make any changes to its recommendations regarding the use of RotaTeq®.