BACKGROUND

In July 2006, Priorix-Tetra™, a combined measles-mumps-rubella-varicella (MMRV) vaccine, was licensed in Germany. Since a postlicensure study had shown a more than twofold elevated risk of febrile convulsions (FC) after first dose vaccination with the combined MMRV vaccine ProQuad(®) compared to separately administered MMR and V vaccines (MMR+V), the Paul-Ehrlich-Institute, the German regulatory agency for vaccine licensing and safety, requested a study investigating the risk of FC for Priorix-Tetra™.

METHODS

We performed a matched cohort study based on claims data of more than 17 million insurees in the German Pharmacoepidemiological Research Database. All children born between 01.01.2004 and 31.12.2008 who received a 1st dose of MMRV vaccine were matched to children vaccinated with MMR, MMR+V and MMR or MMR+V (combined group), respectively, by sex, age, month of vaccination and statutory health insurance. The primary outcome was defined as hospitalization with a diagnosis of FC without any alternative plausible cause of FC, e.g. an infection or neurological condition, coded as main discharge diagnosis. The secondary outcome excluded only neurological conditions to provide a more comparable outcome definition to the one used in the ProQuad(®) study. Numbers needed to harm (NNH), risk ratios and confounder adjusted odds ratios (ORs) with 95% CIs were estimated to compare the exposure groups.

RESULTS

In the main risk period 5-12 days after immunization, the adjusted ORs of the primary endpoint for immunization with MMRV vaccine relative to the comparator vaccine indicated in brackets were 4.1 [95% CI 1.3-12.7; MMR], 3.5 [0.7-19.0; MMR+V], and 4.1 [1.5-11.1; MMR and MMR+V]. The corresponding ORs for the secondary outcome were 2.3 [1.4-3.9; MMR], 1.5 [0.8-2.9; MMR+V] and 2.4 [1.5-3.9; MMR and MMR+V].

CONCLUSIONS

This study in children younger than 5 years, 90% of them between 11 and 23 months, shows a risk of FC similar in magnitude for Priorix-Tetra™ as has previously been reported for ProQuad(®) suggesting a class effect for these quadrivalent vaccines.