High-Dose vs Standard-Dose Influenza Vaccine in Chronic Kidney Disease: The DANFLU-2 Trial Subgroup Analysis
- PMID: 41295932
- DOI: 10.1016/j.jacc.2025.10.005
High-Dose vs Standard-Dose Influenza Vaccine in Chronic Kidney Disease: The DANFLU-2 Trial Subgroup Analysis
Abstract
Background: Influenza-related complications occur frequently in persons with chronic kidney disease (CKD). Limited data exist on the effectiveness of high-dose inactivated influenza vaccine (HD-IIV) in persons with CKD.
Objectives: The purpose of this study was to assess the relative effectiveness (rVE) of HD-IIV vs standard-dose inactivated influenza vaccine (SD-IIV) against severe clinical outcomes in persons with CKD from the elderly general population.
Methods: DANFLU-2 (A Pragmatic Randomized Trial to Evaluate the Effectiveness of High-Dose Influenza Vaccine vs. Standard-Dose Influenza Vaccine in Older Adults) was a pragmatic, open-label, individually randomized trial conducted in Denmark during the 2022-2023, 2023-2024, and 2024-2025 influenza seasons with the aim of assessing the rVE of HD-IIV vs SD-IIV in an older adult general population. In this prespecified secondary analysis, we assessed the rVE against severe clinical outcomes according to the presence of CKD. CKD was defined using data from laboratory registries and International Classification of Diseases-10th Revision diagnosis codes 10 years before vaccination.
Results: Among 332,438 DANFLU-2 participants (mean age 73.7 ± 5.8 years; 48.6% women), 46,788 (14.1%) had CKD at baseline. The effect of HD-IIV vs SD-IIV on hospitalization for influenza or pneumonia differed by CKD status: rVE was 16.9% (95% CI: 3.4%-28.5%) in participants with CKD vs 0.6% (95% CI: -9.6% to 9.9%) in those without CKD (P interaction = 0.046). Absolute risks for hospitalization for influenza or pneumonia were 1.7% with SD-IIV vs 1.3% with HD-IIV in CKD, corresponding to an absolute risk reduction of -0.29% (95% CI: -0.50% to 0.058%; number needed to treat [NNT] = 359). For influenza hospitalizations specifically, the benefit of HD-IIV was also substantially greater in CKD: rVE 68.6% (95% CI: 46.7%-82.3%; NNT = 561) vs 30.6% (95% CI: 7.2%-48.2%; NNT =3,953) in non-CKD (P interaction = 0.0079). Reductions in hospitalizations for cardiorespiratory disease, cardiovascular disease, heart failure, and laboratory-confirmed influenza were consistent regardless of CKD (all P interaction > 0.05).
Conclusions: In this prespecified analysis of DANFLU-2, including the largest CKD population ever in an individually randomized vaccine trial, we observed a benefit of HD-IIV vs SD-IIV against hospitalization for influenza or pneumonia, as well as hospitalization for influenza, with suggestion of a greater relative benefit among those with CKD. Furthermore, the beneficial effect of HD-IIV vs SD-IIV on multiple cardiorespiratory outcomes was consistent across participants irrespective of CKD status.
Keywords: chronic kidney disease; high-dose; influenza; pragmatic; randomized controlled trial; registry; risk group; vaccination.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Funding Support and Author Disclosures The trial was funded by Sanofi who participated in the study design, protocol development phase, and study reporting, but had no responsibilities in trial conduct, data collection, or data analysis. Dr Bartholdy was financed by a research grant from the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation and The Danish Heart Foundation (NNF20SA0067242). Drs Loiacono, Harris, and Dufournet are full-time employees of Sanofi and may own shares and/or stock options in the company. The authors did not require industry approval to submit or publish this paper. Dr Larsen has received speaker fees and served on advisory boards for GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, Takeda, and Valneva. Dr Claggett has received consulting fees from Amgen, Cardurion, Corvia, Myokardia, and Novartis. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GlaxoSmithKline, 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. Dr Landray has received institutional research grants from Novartis, Sanofi, Regeneron, Moderna, GlaxoSmithKline, and Boehringer Ingelheim. Dr Køber has received speaker fees from Novo Nordisk, Novartis, AstraZeneca, Boehringer Ingelheim, and Bayer. Dr Biering-Sørensen has received research grants from Bayer, Novartis, Pfizer, Sanofi Pasteur, GlaxoSmithKline, Novo Nordisk, AstraZeneca, Boston Scientific, and GE Healthcare; has received consulting fees from Novo Nordisk, IQVIA, Parexel, Amgen, CSL Seqirus, GlaxoSmithKline, and Sanofi Pasteur; and has received lecture fees from AstraZeneca, Bayer, Novartis, Sanofi Pasteur, GE Healthcare, and GlaxoSmithKline. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.