Safety of Rotarix™ and Rotateq™ rotavirus vaccines
Following the withdrawal of the first licensed rotavirus vaccine (a tetravalent rhesus reassortant rotavirus vaccine, commercially known as Rotashield®) from the United States market because of its association with an incidence of intussusception among recipients of about 1 per 10 000, two newly-developed rotavirus vaccines, Rotarix™ (GSK Biologicals) and Rotateq™ (Merck Research Laboratories), have been developed and licensed for use in a number of countries. At its meetings in December 2004 and December 2005, the Global Advisory Committee on Vaccine Safety (GACVS) reviewed efficacy and safety data that were accumulating from the Phase III trials, provided to the Committee in confidence by the two companies developing the vaccines. The results from these trials have now been published and confirm the high efficacy of both vaccines against severe rotavirus diarrhoea and the absence of evidence of an increased risk of intussusception associated with either vaccine. In the trial of the Rotarix™ conducted on over 60 000 infants from 11 Latin American countries and Finland, 25 cases of definite intussusception were reported, nine in the vaccine group and 16 in the placebo group. Of these 25 cases, 13 were reported within 31 days of a vaccine (or placebo) dose, six in the vaccine group and seven in the placebo group. A further three cases in the vaccine group and nine in the placebo group were reported after this 31-day window (median duration of total safety surveillance was 100 days after the first dose). In the trial of Rotateq™ conducted on approximately 70 000 infants in 11 countries in North America, Latin America and Europe, there were 12 cases of intussusception among vaccine recipients and 15 among placebo recipients within one year of the first dose, and six and five respectively within 42 days of any dose. In neither trial was there evidence of an excess of other serious adverse effects among vaccine recipients.
In considering these findings, the Committee concluded that the pre-licensing safety profiles derived from the Phase III trials of the current vaccines were reassuring. However, the confidence intervals on the intussusception risks were wide and the Committee considered that the possibility remained of a risk of intussusception or of other adverse effects during routine use of the vaccines. Post-marketing surveillance will be key to addressing safety issues at a population level. The GACVS reiterated the importance of a commitment to post-marketing surveillance in developing countries, including those where the current capacity to conduct such studies was inadequate.
At its meeting in June 2006, the GACVS noted that WHO is developing a generic protocol for post-marketing surveillance of rotavirus vaccine safety that can be adapted at country level for implementation. This protocol includes monitoring of intussusception as well as other potential safety issues, including other gastrointestinal symptoms, the potential effect of malnutrition, and shedding and transmission of vaccine virus strains. WHO will also support the post-marketing surveillance of rotavirus vaccine safety through a network of sentinel countries.
The Committee also noted that plans are underway, under the leadership of the United States Centers for Disease Control and Prevention, to develop and make available a protocol for the post-marketing surveillance for the impact of rotavirus vaccine.
The Committee strongly recommended that introduction of rotavirus vaccines should be associated with careful consideration of post-marketing surveillance at country level and securing its funding as an essential part of immunization programmes.