Efficacy and safety of high-dose influenza vaccine in elderly adults: A systematic review and meta-analysis

Introduction: Older adults are prioritized for influenza vaccination but also have lowered antibody responses to the vaccine. Higher-doses of influenza antigen may increase immune response and thus be more effective. Our objectives were to compare the efficacy and safety of the high-dose influenza vaccine to the standard-dose influenza vaccine in the elderly (age > 65). Methods: Data sources: Randomized trials (RCTs) from Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley), ClinicalTrials.gov, reference lists of relevant articles, and gray literature. Study selection: Two reviewers independently identified RCTs comparing high-dose influenza vaccine (60 mu g of hemagglutinin per strain) to standard-dose influenza vaccine (15 mu g of hemagglutinin per strain) in adults over the age of 65 years. Data extraction: Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the Cochrane Risk of Bias tool. Results: We included seven eligible trials; all were categorized as having a low (n = 3) or unclear (n = 4) risk of bias. Patients receiving the high-dose vaccine had significantly less risk of developing laboratory confirmed influenza infections (Relative Risk 0.76, 95%CI 0.65 to 0.90; I-2 0%, 2 trials, 41,141 patients). Post-vaccination geometric mean titres and seroprotection rates were also higher in high-dose vaccine recipients. There were no protocol-defined serious adverse events in the included trials in either group. Conclusions: In elderly adults, the high-dose influenza vaccine was well-tolerated, more immunogenic, and more efficacious in preventing influenza infections than the standard-dose vaccine. Further pragmatic trials are needed to determine if the higher efficacy translates into higher vaccine effectiveness in adults over the age of 65. (C) 2017 Elsevier Ltd. All rights reserved.