A systematic review of the literature was conducted to provide evidence to inform recommendations on using ATIV for the prevention of influenza in children aged 6 to 72 months. Only 8 articles met all pre-specified inclusion criteria, of which 7 articles were from clinical trials that compared ATIV with a UTIV comparator and one from a study that looked at ATIV in healthy children compared to children with juvenile arthritis.
Based on this review, information on comparative efficacy is available only from a single trial suggesting a higher efficacy for ATIV (86% vs. 40% for comparator UTIV). The bulk of the data was obtained during one mild season that was dominated by influenza A/H3N2. The comparator vaccine induced a poorer immune response compared to equivalent UTIVs. There were also concerns raised by a European Medicine Agency inspection about the quality of diagnostic laboratory testing and validity of ascertainment of influenza cases.
There is limited but consistent evidence that ATIV is more immunogenic than comparable UTIVs against influenza A types. In particular, a single dose of ATIV is more immunogenic than a single UTIV dose. However, two doses of ATIV are still necessary to achieve satisfactory immune response against influenza B. As immunogenicity is an intermediate outcome, it is unclear what clinical protection is conferred.
Literature Review on Pediatric Fluad® Influenza Vaccine use in Children 6-72 Months of Age ATIV was not compared directly to LAIV or to the quadrivalent influenza vaccine (QIV). One study using a dose-ranging factorial design with adjuvanted and unadjuvanted versions of seasonal TIV and QIV was identified, but a comparison of ATIV and QIV was not the primary objective of the study and the data were not grouped appropriately for such a comparison. Clinical trials comparing efficacy, immunogenicity, and safety of a single- and two-dose regimes of ATIV, LAIV and QIV are needed.
Safety data for ATIV in children is consistent with what is known about ATIV safety in adults. ATIV results in 10-15% more solicited local and systemic reactions compared to UTIV.
However, most reactions are mild and tend to resolve quickly. Severe reactions are rare, but several of the reviewed studies were too small to detect clinically significant but rare adverse events. In particular, the safety information is limited for ATIV in children with immunodeficiencies and other chronic illnesses.
Taken together, the limited body of evidence identified in this review suggests that ATIV is likely both more immunogenic and more reactogenic than UTIV among children 6-72 months of age. There are insufficient data to assess whether ATIV is more effective than UTIV or LAIV in practice or to make an informed risk-benefit analysis.