High-dose versus standard-dose influenza vaccine for immunocompromised patients: A systematic review and meta-analysis of randomised clinical trials

Abstract

Background: Immunocompromised patients present a higher risk of severe influenza disease and respond worse to vaccination. Objective: We aimed to assess immunogenicity and safety of high-dose vs. standard-dose influenza vaccine in immunocompromised patients. Data source: A search was conducted in Medline, Web of Science, Scopus and ClinicalTrials.gov from inception to March 2024 with no other restrictions. Study eligibility: Randomised clinical trials reporting immunogenicity or safety of high-dose versus standard-dose influenza vaccine in immunocompromised patients were included. Methods: The protocol was prospectively registered (PROSPERO ID: CRD42023466202). A meta-analysis was conducted using random-effects models. Heterogeneity was assessed through I2 statistic. Subgroup analyses were conducted, and publication bias was assessed through funnel plots and Egger’s tests. Results: A total of 21 analyses from 16 randomised clinical trials were included. Regarding immunogenicity (including 1862 patients), high-dose influenza vaccine showed higher geometric mean titre of hemagglutination inhibition and higher seroconversion rates for all strains (RR=1.30, 95%CI:1.04–1.57, I2=45.0% for H1N1; RR=1.22, 95%CI:1.03–1.41, I2=39.5% for H3N2; RR=1.39, 95%CI:1.15–1.63, I2=18.1% for B). These findings were reinforced in studies with higher methodological quality and higher sample sizes. Regarding safety (including 1403 patients), there were no differences in reported adverse events except for pain, higher in the high-dose influenza vaccine group (RR=1.29, 95%CI:1.04–1.54). Although high-dose influenza vaccine showed less frequency of clinical outcomes, data were not conclusive as few studies analysed clinical effectiveness. Conclusions: High-dose influenza vaccine showed higher immunogenicity and similar safety than standarddose vaccine and should be recommended for immunocompromised patients. Future larger randomised clinical trials analysing clinical effectiveness are required to provide recommendations for specific immunocompromised populations.