Rotavirus vaccine safety
The Committee was asked to consider whether the use of tetravalent rhesus reassortant rotavirus vaccine (commercially known as RotaShield®) might be associated with a significantly lower risk of vaccine-induced intussusception if immunization is completed before 2 months of age. This had been suggested in a recent publication of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States, in the Journal of Infectious Diseases. The Committee will continue to review the safety data of new rotavirus vaccines from clinical trials and post-marketing surveillance. It noted that the possibility of an age-dependent risk of intussusception should be taken into account in assessing rotavirus vaccines.
The Committee studied a re-analysis of the original case-control study data from the United States Centers for Disease Control and Prevention (CDC), which showed a lower relative risk of intussusception in infants immunized before 60 days of age than those immunized later in infancy. The authors concluded that the relative risk of intussusception might be substantially reduced if a neonatal immunization schedule is used rather than the vaccination strategy in older infants that had been used in the introduction of the vaccine in the United States. It was suggested to the Committee that an age-dependent risk of intussusception might also apply to the 2 novel rotavirus vaccines that are currently in advanced development. The Committee noted that although the point estimates of relative risk differed between older and younger infants, the confidence intervals on the estimates overlapped substantially and the differences were not statistically significant.
Representatives from CDC, who where involved with the initial analysis and investigation of the association between RotaShield® and intussusception, presented the Committee with a re-analysis of the initial data set. The CDC confirmed a high relative risk in infants immunized after day 60. Too few children had been immunized before day 60 in the CDC studies to assess adequately the hypothesis of a lower relative risk in younger infants. No efficacy data are available using a neonatal schedule for any of the rotavirus vaccines.
The Committee concluded as follows:
- The studies provide clarification and confirmation of a high risk of RotaShield®-associated intussusception in infants immunized after day 60.
- The available evidence is not sufficient to conclude that the use of RotaShield® at an age less than 60 days is associated with a lower relative risk of intussusception.
- Even strict recommendations for adherence to an early immunization schedule would be extremely difficult to implement in the field in many countries.
The Committee will continue to review the safety data of new rotavirus vaccines from clinical trials and post-marketing surveillance. It noted that the possibility of an age-dependent risk of intussusception should be taken into account in assessing rotavirus vaccines.