Relative effectiveness of high-dose versus standard-dose influenza vaccine against hospitalizations and mortality according to Charlson Comorbidity Index: A post-hoc analysis of the DANFLU-1 randomized trial.
Bernholm KF., Johansen ND., Espersen C., Modin D., Hyldekær KJ., Nealon J., Samson S., Loiacono MM., Harris RC., Larsen CS., Jensen AMR., Landler NE., Nielsen ST., Russell L., Itenov TS., Claggett BL., Solomon SD., Landray MJ., Gislason GH., Køber L., Sivapalan P., Jensen JUS., Biering-Sørensen T.
PURPOSE: The DANFLU-1 trial suggested lower incidence of hospitalizations for pneumonia and influenza, respiratory disease and all-cause mortality among older adults receiving high-dose (HD-IV) versus standard-dose (SD-IV) influenza vaccine. This study assessed the relative effectiveness of HD-IV versus SD-IV according to comorbidity in elderly individuals. METHODS: This was a post-hoc analysis of the DANFLU-1 randomized controlled feasibility trial of HD-IV versus SD-IV conducted during the 2021-2022 influenza season in adults aged 65-79 years. Outcomes assessed included influenza-related, respiratory, and cardiovascular hospitalizations, and mortality. We tested for effect modification by level of the Charlson Comorbidity Index (CCI) using ICD-10 codes up to 10 years prior to randomization. RESULTS: Of the 12,477 randomly assigned participants (mean age 71.7 ± 3.9 years, 47.1% female), 8,020 (64.3%) had CCI = 0, 3,560 (28.5%) had CCI = 1-2 and 893 (7.2%) had CCI ≥ 3. When comparing HD-IV with SD-IV, hazard ratios of hospitalizations for pneumonia and influenza were similar across CCI groups (HR [95%CI]: 0.15 [0.03-0.68] for CCI = 0, 0.36 [0.11-1.15] for CCI = 1-2, 1.00 [0.25-4.00] for CCI ≥ 3). Comparable patterns were found for hospitalizations for respiratory disease (0.46 [0.17-1.20] for CCI = 0, 0.67 [0.32-1.39] for CCI = 1-2, 0.66 [0.24-1.87] for CCI ≥ 3) and all-cause mortality (0.28 [0.09-0.86] for CCI = 0, 0.70 [0.30-1.63] for CCI = 1-2, 0.57 [0.24-1.36] for CCI ≥ 3). There was no statistical evidence of effect modification by CCI for any outcome. CONCLUSIONS: The lower incidences of clinical outcomes for HD-IV compared to SD-IV were not significantly modified by CCI. The potential benefit of HD-IV versus SD-IV may therefore be applicable regardless of comorbidity burden. Further research is required to confirm these findings.