Tuesday, March 18, 2008

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

Kenneth M. Zangwill1, Eileen M. Eriksen1, Martin Lee1, Jennifer Y. Lee1, Leonard Friedland2, Wayde Weston2, Barbara J Howe2, S. Michael Marcy3, and Joel I. Ward1. (1) UCLA Center for Vaccine Research, Harbor-UCLA Medical Center, Torrance, CA, USA, (2) GlaxoSmithKline Biologicals, King of Prussia, PA, (3) Kaiser Foundation Hospital, Kaiser Permanente of Southern California, Panorama City, CA, USA

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.

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

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

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).

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.

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.