Objectives: The most robust way to assess the relative safety profile of vaccines data obtained from multiple randomized clinical trials is to run individual patient data meta-analyses (IPD-MA). Having access to individual subject data of six randomized head-to-head controlled trials of two hexavalent vaccines [DTaP-IPV-HB-PRP~T (Hexaxim) and DTaP-IPV-HB//PRP~T (Infanrix-Hexa)] we ran an IPD-MA to describe the relative safety profile of the two hexavalent vaccines based on a list of specific safety endpoints.

Methods: A one-stage IDP-MA was performed using a multivariate mixed effects model. Relative risks (RR), absolute risk reductions (ARR) and numbers of subjects needed to vaccinate to see an adverse event with their respective 95% confidence intervals (CI) were estimated for the pre-specified list of adverse events assessed in vaccine studies (local, systemic and serious AEs). Sensitivity analyses were performed with unadjusted and multivariate logistic model.

Results: A total of 4311 subjects were included (2926 received DTaP-IPV-HB-PRP~T and 1385 DTaP-IPV-HB//PRP~T). Because of the large sample size, RRs and ARRs were statistically different but not necessarily clinically meaningful for most events, although with very low relative risks (< 1.7) and absolute risk differences (<8%). For grade 3 reactions, all required at least 30 subjects needed to be vaccinated to see one extra adverse event, those with the lowest numbers were subjective measures as crying, irritability, and pain.

Conclusion: DTaP-backboned hexavalent vaccines are safe and, depending on the safety endpoint explored, some minor differences (all RRs were close to 1) in favor of one vaccine over the other were noted. As AEs were solicited, they may not reflect what HCPs and parents may consider significant AE in real life. Translated in daily medical practice these differences are clinically meaningless and should not constitute an argument in favor of one vaccine over the other.