Effects of high-dose versus standard-dose influenza vaccine among patients with chronic lung disease: A prespecified analysis of the DANFLU-1 trial.
Duus LS., Johansen ND., Modin D., Janstrup KH., Nealon J., Samson S., Loiacono MM., Harris RC., Larsen CS., Reimer Jensen AM., Claggett BL., Solomon SD., Landray MJ., Gislason GH., Køber L., Sivapalan P., Stæhr Jensen JU., Biering-Sørensen T.
BACKGROUND: Individuals with chronic lung disease (CLD) face an increased risk of influenza-related complications and mortality, and seasonal vaccination is recommended. Limited evidence exists on the effectiveness of high-dose (HD-IIV) vs. standard-dose (SD-IIV) inactivated influenza vaccines in this population. METHODS: DANFLU-1 trial was a pragmatic, open-label, randomized trial comparing HD-IIV vs. SD-IIV in adults aged 65-79 years during the 2021/2022 influenza season. Vaccines were allocated 1:1. CLD was identified using ICD-10 codes. The prespecified outcomes were hospitalizations due to pneumonia or influenza, respiratory, cardiovascular, cardiorespiratory, and all-cause hospitalizations, and mortality. RESULTS: The study population included 12,477 participants (mean age 71.7 ± 3.9 years, 47 % female), of whom 850 (6.8 %) had CLD. Hospitalization rates for all outcomes were significantly higher among participants with CLD. HD-IIV was associated with a lower risk of hospitalization for pneumonia or influenza (HR 0.36 (CI: 0.17-0.73); no CLD: HR 0.22 (CI: 0.08-0.57); CLD: HR 0.95 (CI: 0.28-3.30); p for interaction = 0.064), respiratory hospitalization, and all-cause mortality, and a lower incidence rate of all-cause hospitalization. Effect estimates were less favorable for HD-IIV compared to SD-IIV among CLD patients in preventing respiratory disease hospitalization and all-cause mortality. CONCLUSION: In this prespecified analysis of the DANFLU-1 randomized trial of HD-IIV vs. SD-IIV, trends suggested that among participants with CLD, the benefit of HD-IIV may be attenuated compared with those without CLD, particularly in relation to respiratory disease hospitalization and all-cause mortality. Given the small sample size, these results should be considered hypothesis-generating and require further investigation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05048589.