Safety and Reactogenicity of a Novel DTPa-HBV-IPV Combined Vaccine Given Along With Commercial Hib Vaccines inComparison With Separate Concomitant Administration ofDTPa, Hib, and OPV Vaccines in Infants

Abstract

ABSTRACT. Objective. Combination vaccines simplify vaccine administration and have the potential to promote compliance and cost-effectiveness by decreasing the number of injections needed to immunize a child. The objective of this study was to assess the safety and reactogenicity of the diphtheria-tetanus toxoid-acellular pertussis-hepatitis B virus-inactivated polio virus (DTPa-HBV-IPV) vaccine when coadministered with different Haemophilus influenzae type B (Hib) vaccines in comparison with separate, commercially available, control vaccines in a 3-dose primary vaccination series.Methods. An open-label, randomized, parallel-group study in 5318 infants who were 8 to 16 weeks of age at enrollment was conducted in 90 centers in Germany. The incidence of adverse events that occurred in infants who received the DTPa-HBV-IPV candidate vaccine coadministered with 1 of 4 different Hib vaccines (given in separate sites; groups 1-4) was compared with the incidence that occurred in infants who received commercially available control vaccines (DTPa, Hib, and oral polio virus [OPV] vaccine; group 5) administered separately. The vaccines were given as a 3-dose primary series at 3, 4, and 5 months of age. Infants were assessed for solicited local and general adverse events for 4 days and for unsolicited adverse events for 30 days after each vaccine dose. The primary endpoint was to rule out a 7.5% increase in infants who experienced grade 3 (defined as preventing normal everyday activities unless otherwise specified) solicited local and general adverse events over the 3-dose primary course after the combined DTPa-HBV-IPV vaccine coadministered with Hib as compared with commercially available vaccines.Results. During the 3-dose primary course, 490 of 3029 infants (16.2%) in the pooled DTPa-HBV-IPV vaccine groups and 151 of 744 (20.3%) in the control vaccine group experienced a grade 3 adverse event (rate difference [control minus combination] 4.1%; 90% confidence interval, 1.41-7.13). The lower limit of the 90% confidence interval of the observed difference remained above the prespecified ؊7.5% limit for noninferiority, thereby meeting the primary endpoint. The incidences of local injection-site reactions were similar for the DTPa-HBV-IPV and DTPa injection sites. Significant differences in the incidence of both local and general adverse events were observed depending on which of the Hib vaccines was coadministered. Infants who received Hib N meningitidis outer-membrane complex protein conjugate vaccine had greater incidences of fever and, to a lesser extent, greater reactions at the Hib injection site than did infants who received other Hib vaccines.Conclusions ABBREVIATIONS. DTPa, diphtheria-tetanus toxoid-acellular pertussis; HBV, hepatitis B virus; Hib, Haemophilus influenzae type b; IPV, inactivated polio virus; OPV, oral polio virus; ATP, according-to-protocol; ITT, intention-to-treat; CI, confidence interval; PRP-OMP, Haemophilus influenzae type b Neisseria meningitidis outer-membrane complex protein conjugate.

A Population-Based, Postlicensure Evaluation of the Safety of a Combination Diphtheria, Tetanus, Acellular Pertussis, Hepatitis B, and Inactivated Poliovirus Vaccine in a Large Managed Care Organization

“…9 These data led to concerns that postvaccination fever might result in clinically relevant consequences, such as seizures, medical visits, and/or diagnostic evaluation. [6][7][8][9]19 This and other prospective prelicensure studies required parents to record daily temperatures regardless of clinical significance. In our study we evaluated this vaccine as used in routine clinical practice and the proportion of visits associated with postvaccination fever in each cohort was very small (Ͻ0.3%), the majority did not require diagnostic testing, and a cause of fever was rarely identified.…”

“…This is consistent with prelicensure data. [6][7][8][9] Seizures have been associated with receipt of DTaP, measles-mumps-rubella vaccine, 20 and measles-mumps-rubella-varicella vaccine, 21 particularly in association with fever. The cause of this phenomenon remains obscure, but generally most seizures in infants are associated with fever, and fever probably precipitates most vaccine-associated seizures as well, which are generally not serious.…”

“…Prelicensure evaluations of this vaccine included ϳ8100 infants and noted it to be immunogenic, generally safe, and unlikely to result in vaccine-associated serious adverse events. [6][7][8][9][10] Some clinical trial data show an increased incidence of fever after DTaP-HepB-IPV vaccination, compared with separately administered vaccines. [9][10][11] The clinical significance of this finding remains unclear.…”

Cost-Benefit Analysis of Haemophilus Influenzae Type B Immunization in Korea

“…To adjust the severity of disability due to Hib, the Health Utility Index (HUI) (18) was applied to the calculation: 0.840 for hemiplgia, epilepsy, and mental retardation and 0.977 for severe hearing loss (19). The HUI is a value assigned to the quality of life, calculating a weighted coefficient for each health state and adopted in relation to the age of patient.…”

Vaccines and immunotherapies for the prevention of infectious diseases having cutaneous manifestations

“…113,115 Furthermore, administration of DTaP-HepB-IPV together with Hib vaccine was associated with higher rates of fever in comparison with separately administered vaccines. 112,116 The FDA has approved Pediarix for use in infants aged 2, 4, and 6 months. The Advisory Committee on Immunization Practices recommends that for infants who are born to women who are HBsAgpositive or whose HBsAg status is unknown, a birth dose of single-antigen vaccine is preferred, but the birth dose can then be followed by 3 doses of Pediarix at ages 2, 4, and 6 months.…”