Hexavalent vaccines in infants: a systematic literature review and meta-analysis of the solicited local and systemic adverse reactions of two hexavalent vaccines

Abstract

Introduction:The hexavalent vaccine DT3aP-HBV-IPV-Hib (Infanrix hexa, GSK) was first licensed in Europe in 2000. DT2aP-HBV-IPV-Hib (Hexyon/Hexacima/Hexaxim, Sanofi Pasteur), and DT5aP-HBV-IPV-Hib (Vaxelis, MCM Vaccine Company) were licensed in the EU in 2013 and 2016, respectively, based largely on studies demonstrating non-inferiority to DT3aP-HBV-IPV-Hib for immunogenicity and comparable reactogenicity profiles. Methods: We conducted a systematic literature review looking for direct head-to-head trials comparing DT2aP-HBV-IPV-Hib and DT5aP-HBV-IPV-Hib with DT3aP-HBV-IPV-Hib. The incidence of solicited local and systemic reactions following primary series administration of DT3aP-HBV-IPV-Hib or DT2aP-HBV-IPV -Hib were meta-analyzed. Results: A total of 317 unique records were retrieved from the search; nine met the predefined inclusion criteria; seven reported studies comparing DT3aP-HBV-IPV-Hib and DT2aP-HBV-IPV-Hib. Six trials assessing outcomes of the primary vaccination series were identified. Odds ratios and 95% confidence intervals (OR; 95%CI) were computed for DT3aP-HBV-

Changes in vaccination practices among infants after the introduction of DTaP-IPV/Hib combination vaccines

“…DTaP-IPV-Hib-HepB combination vaccine (Sanofi Pasteur) was approved in Korea on April 6, 2020, but has not yet been introduced into the NIP [19] . Many countries including the United States, United Kingdom, Australia, and Canada, have already introduced the DTaP-IPV-Hib-HepB combination vaccine into their NIPs based on its high safety and immunogenicity profile [20] . Korea recently conducted a cost-effectiveness analysis of the DTaP-IPV-Hib-HepB combination vaccine, which demonstrated the potential to reduce costs by $36.22 per infant and a total savings of $9,236,417 compared to the DTaP-IPV/Hib combination vaccine [21] .…”

Reduced reactogenicity of primary vaccination with DT3aP-HBV-IPV/Hib compared with DT2aP-HBV-IPV-Hib among infants: Mathematical projections in six countries

“…A decision-support differentiation tool was developed using Microsoft Excel 2016 to compare the reactogenicity profiles of the hexavalent vaccines DT3aP-HBV-IPV/Hib and DT2aP-HBV-IPV-Hib. The inputs used in the decision-support tool were based on results from a systematic literature review of randomized clinical trials and a meta-analysis of immunological and safety outcomes by Mukherjee et al 18 The mathematical projection tool was applied to the infant population of six countries: Austria, the Czech Republic, France, Jordan, Spain, and the Netherlands. The country-specific assumptions, such as the number of infants born in 2020, the projected number of infants born between 2023 and 2027 based on population growth estimates, and the vaccination coverage, are shown in Table S1.…”

“… 15–17 However, a systematic literature review and meta-analysis of head-to-head studies in infants that analyzed the adverse reactions (ARs) to the two hexavalent vaccines found that the odds ratios of local and systemic solicited ARs following the primary vaccination of infants were lower with DT3aP-HBV-IPV/Hib than with DT2aP-HBV-IPV-Hib. 18 In addition, some significant differences in reactogenicity profiles were noted in another systematic literature review of head-to-head studies comparing DT3aP-HBV-IPV/Hib and DT2aP-HBV-IPV-Hib. 14 …”

Recommendation for use of diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b conjugate, and hepatitis B vaccine in infants

“…9) Their composition and formulation differ slightly, but all have shown good immunogenicity and safety profiles. [9][10][11] Hexyon ® and Hexacima ® are the same products as Hexaxim®, with the only differences being their brand names depending on the country of sale. 9) As of 2021, only Hexaxim ® has been introduced in Korea.…”

“…There are currently 3 hexavalent vaccine preparations approved for use worldwide: Infanrix-hexa (GSK, Rixensart, Belgium); Hexyon/Hexacima/Hexaxim (all Sanofi Pasteur); and Vaxelis (MSP Vaccine Co., Swiftwater, PA, USA) [ 9 ]. Their composition and formulation differ slightly, but all have shown good immunogenicity and safety profiles [ 9 - 11 ]. Hexyon and Hexacima are the same products as Hexaxim, with the only differences being their brand names depending on the country of sale [ 9 ].…”