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Randomized Controlled Trial
. 2025 Nov;63(6):1309-1315.
doi: 10.1016/j.resinv.2025.10.016. Epub 2025 Nov 1.

Effects of high-dose versus standard-dose influenza vaccine among patients with chronic lung disease: A prespecified analysis of the DANFLU-1 trial

Lisa Steen Duus  1 , Niklas Dyrby Johansen  1 , Daniel Modin  1 , Kira Hyldekær Janstrup  1 , Joshua Nealon  2 , Sandrine Samson  2 , Matthew M Loiacono  3 , Rebecca C Harris  4 , Carsten Schade Larsen  5 , Anne Marie Reimer Jensen  1 , Brian L Claggett  6 , Scott D Solomon  6 , Martin J Landray  7 , Gunnar H Gislason  8 , Lars Køber  9 , Pradeesh Sivapalan  10 , Jens Ulrik Stæhr Jensen  10 , Tor Biering-Sørensen  11
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Free article
Randomized Controlled Trial

Effects of high-dose versus standard-dose influenza vaccine among patients with chronic lung disease: A prespecified analysis of the DANFLU-1 trial

Lisa Steen Duus et al. Respir Investig. 2025 Nov.
Free article

Abstract

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.

Keywords: Asthma; Chronic obstructive pulmonary disease; Influenza; Pragmatic; Randomized controlled trial.

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Conflict of interest statement

Declaration of competing interest JN, SS, MML, and RCH, are full-time employees of Sanofi and may own shares and/or stock options in the company. CSL is group medical director for European LifeCare Group. He has received fees for lectures and participation in advisory boards from Astra Zeneca, Bavarian Nordic, GSK, Moderna, MSD, Pfizer, and Takeda. BLC has received consulting fees from Amgen, Cardurion, Corvia, Myokardia, and Novartis. SDS has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi, Theracos, US2.AI and consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health. MJL has received institutional research grants from Sanofi, GSK, Regeneron, Moderna, Novartis, and Apollo Rx. LK has received speaker fees from Novo Nordisk, Novartis, AstraZeneca, Boehringer Ingelheim, and Bayer. TBS has received research grants from Bayer, Novartis, Pfizer, Sanofi Pasteur, GSK, Novo Nordisk, AstraZeneca, Boston Scientific, and GE Healthcare, consulting fees from Novo Nordisk, IQVIA, Parexel, Amgen, CSL Seqirus, GSK and Sanofi Pasteur, and lecture fees from AstraZeneca, Bayer, Novartis, Sanofi Pasteur, GE healthcare and GSK. All other authors have nothing to declare.

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