Post-licensure Safety Evaluation of a DTaP-HepB-IPV Combination Vaccine in a Large Managed Care Organization

Learning Objectives for this Presentation:
By the end of the presentation participants will understand the safety profile of DTaP-HepB-IPV vaccine in young infants.

Background:
Prelicensure studies suggested that DTaP-HepB-IPV combination vaccine (Pediarix™) may result in higher rates of fever than its component antigens given separately.

Objectives:
To determine the frequency of selected adverse events following DTaP-HepB-IPV vaccination.

Methods:
Prospective, controlled cohort study to evaluate adverse events (AEs) following receipt of DTaP-HepB-IPV vaccine in the Kaiser Permanente Southern California Health Care Plan. From 4/2003 through 6/2005, we accrued 61,005 infants (120,000 doses) who received at least 1 dose of DTaP-HepB-IPV vaccine. This cohort was compared to a cohort of 58,251 age, sex, and medical-center matched infants (116,637 doses) who received DTaP vaccine from 1/2002 through 3/2003. We evaluated the occurrence of chart review-verified seizures and medically-attended fever (temperature >=38°C). For the latter, 22,500 visits/cohort were randomly selected for chart review after exclusion of those with diagnoses incompatible as an AE (e.g. followup for head trauma).

Results:
In the DTaP-HepB-IPV and DTaP cohorts respectively, we identified 16 infants (8 with fever) and 15 (6 with fever) who had a seizure post-vaccination and 60 and 48 infants with a medical visit with fever following vaccination. The proportions of children with seizures (0.01; [0.01, 0.02 95% CI]) and seizures associated with fever (0.01; [0.0, 0.01]) within 8 days of vaccination were not statistically different from the comparator group. Similarly, the proportion of infants in the DTaP-HepB-IPV group did not significantly vary with respect to medically-attended fever w/in 4d (0.27, [0.2, 0.34]), allergic reactions w/in 48h (0.04; [0.03, 0.05]), outpatient visits (16.9; 16.7, 17.2]), and hospitalizations w/in 21d (0.3; 0.27, 0.34]) from the comparator group.

Conclusions:
In this large study, we did not observe significant differences in selected safety endpoints following DTaP-HepB-IPV vaccination, in particular all seizures, seizures associated with fever, and medically-attended fever.