tetano
Editor, Senior Moderator
N Engl J Med
. 2025 Aug 30.
doi: 10.1056/NEJMoa2509907. Online ahead of print. High-Dose Influenza Vaccine Effectiveness against Hospitalization in Older Adults
Niklas Dyrby Johansen[SUP] 1 2 [/SUP], Daniel Modin[SUP] 1 2 [/SUP], Matthew M Loiacono[SUP] 3 4 [/SUP], Rebecca C Harris[SUP] 5 [/SUP], Marine Dufournet[SUP] 6 [/SUP], Carsten Schade Larsen[SUP] 7 8 [/SUP], Lykke Larsen[SUP] 9 [/SUP], Lothar Wiese[SUP] 10 [/SUP], Michael Dalager-Pedersen[SUP] 11 12 [/SUP], Brian L Claggett[SUP] 13 [/SUP], Kira Hyldekær Janstrup[SUP] 1 2 [/SUP], Katja Vu Bartholdy[SUP] 1 2 [/SUP], Katrine Feldballe Bernholm[SUP] 1 2 [/SUP], Julie Inge-Marie Helene Borchsenius[SUP] 1 2 [/SUP], Filip Soeskov Davidovski[SUP] 1 2 [/SUP], Lise Witten Davodian[SUP] 1 2 [/SUP], Maria Dons[SUP] 1 2 [/SUP], Lisa Steen Duus[SUP] 1 2 [/SUP], Caroline Espersen[SUP] 1 2 [/SUP], Frederik Holme Fussing[SUP] 1 2 [/SUP], Anne Marie Reimer Jensen[SUP] 1 2 [/SUP], Nino Emanuel Landler[SUP] 1 2 [/SUP], Adam Cadovius Femerling Langhoff[SUP] 1 2 [/SUP], Mats Christian Højbjerg Lassen[SUP] 1 2 [/SUP], Anne Bjerg Nielsen[SUP] 1 2 [/SUP], Camilla Ikast Ottosen[SUP] 1 2 [/SUP], Morten Sengeløv[SUP] 1 2 [/SUP], Kristoffer Grundtvig Skaarup[SUP] 1 2 [/SUP], Scott D Solomon[SUP] 12 [/SUP], Martin J Landray[SUP] 14 [/SUP], Gunnar H Gislason[SUP] 1 15 16 [/SUP], Lars Køber[SUP] 15 17 [/SUP], Line Ralfkiaer[SUP] 18 [/SUP], Joshua Nealon[SUP] 19 [/SUP], Pradeesh Sivapalan[SUP] 15 20 [/SUP], Cyril Jean-Marie Martel[SUP] 21 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 15 20 [/SUP], Tor Biering-Sørensen[SUP] 1 2 17 22 [/SUP]
Affiliations
Background: High-dose inactivated influenza vaccine has been shown to provide protection against influenza that is superior to that with the standard dose. However, data from individually randomized trials on the effectiveness of the high-dose vaccine against severe outcomes are limited.
Methods: In this pragmatic, open-label, randomized, controlled trial conducted in Denmark during the 2022-2023, 2023-2024, and 2024-2025 influenza seasons, we assigned older adults (≥65 years of age) to receive the high dose of the inactivated influenza vaccine or the standard dose. Data collection relied on nationwide administrative health registries. The primary end point was hospitalization for influenza or pneumonia that occurred from 14 days after vaccination through May 31 of the following year.
Results: Of the 332,438 participants who underwent randomization, 166,218 were assigned to receive the high-dose vaccine and 166,220 to receive the standard-dose vaccine. The mean (±SD) age of the participants was 73.7±5.8 years, and 161,538 participants (48.6%) were women. A primary end-point event occurred in 1138 participants (0.68%) in the high-dose group and in 1210 (0.73%) in the standard-dose group (relative vaccine effectiveness, 5.9%; 95.2% confidence interval [CI], -2.1 to 13.4; P = 0.14). Hospitalization for influenza occurred in 0.06% of the participants in the high-dose group and in 0.11% of those in the standard-dose group (relative vaccine effectiveness, 43.6%; 95.2% CI, 27.5 to 56.3); hospitalization for pneumonia occurred in 0.63% and 0.63%, respectively (relative effectiveness, 0.5%; 95.2% CI, -8.6 to 8.8); hospitalization for cardiorespiratory disease in 2.25% and 2.38% (relative effectiveness, 5.7%; 95.2% CI, 1.4 to 9.9); hospitalization for any cause in 9.38% and 9.58% (relative effectiveness, 2.1%; 95.2% CI, -0.1 to 4.3), and death from any cause in 0.67% and 0.66% (relative effectiveness, -2.5%; 95.2% CI, -11.6 to 5.9). The incidence of serious adverse events was similar in the two groups.
Conclusions: In this trial, a high-dose inactivated influenza vaccine did not result in a significantly lower incidence of hospitalization for influenza or pneumonia than a standard dose among older adults. (Funded by Sanofi; DANFLU-2 ClinicalTrials.gov number, NCT05517174; EU Clinical Trials Register number, 2022-500657-17-00.).
. 2025 Aug 30.
doi: 10.1056/NEJMoa2509907. Online ahead of print. High-Dose Influenza Vaccine Effectiveness against Hospitalization in Older Adults
Niklas Dyrby Johansen[SUP] 1 2 [/SUP], Daniel Modin[SUP] 1 2 [/SUP], Matthew M Loiacono[SUP] 3 4 [/SUP], Rebecca C Harris[SUP] 5 [/SUP], Marine Dufournet[SUP] 6 [/SUP], Carsten Schade Larsen[SUP] 7 8 [/SUP], Lykke Larsen[SUP] 9 [/SUP], Lothar Wiese[SUP] 10 [/SUP], Michael Dalager-Pedersen[SUP] 11 12 [/SUP], Brian L Claggett[SUP] 13 [/SUP], Kira Hyldekær Janstrup[SUP] 1 2 [/SUP], Katja Vu Bartholdy[SUP] 1 2 [/SUP], Katrine Feldballe Bernholm[SUP] 1 2 [/SUP], Julie Inge-Marie Helene Borchsenius[SUP] 1 2 [/SUP], Filip Soeskov Davidovski[SUP] 1 2 [/SUP], Lise Witten Davodian[SUP] 1 2 [/SUP], Maria Dons[SUP] 1 2 [/SUP], Lisa Steen Duus[SUP] 1 2 [/SUP], Caroline Espersen[SUP] 1 2 [/SUP], Frederik Holme Fussing[SUP] 1 2 [/SUP], Anne Marie Reimer Jensen[SUP] 1 2 [/SUP], Nino Emanuel Landler[SUP] 1 2 [/SUP], Adam Cadovius Femerling Langhoff[SUP] 1 2 [/SUP], Mats Christian Højbjerg Lassen[SUP] 1 2 [/SUP], Anne Bjerg Nielsen[SUP] 1 2 [/SUP], Camilla Ikast Ottosen[SUP] 1 2 [/SUP], Morten Sengeløv[SUP] 1 2 [/SUP], Kristoffer Grundtvig Skaarup[SUP] 1 2 [/SUP], Scott D Solomon[SUP] 12 [/SUP], Martin J Landray[SUP] 14 [/SUP], Gunnar H Gislason[SUP] 1 15 16 [/SUP], Lars Køber[SUP] 15 17 [/SUP], Line Ralfkiaer[SUP] 18 [/SUP], Joshua Nealon[SUP] 19 [/SUP], Pradeesh Sivapalan[SUP] 15 20 [/SUP], Cyril Jean-Marie Martel[SUP] 21 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 15 20 [/SUP], Tor Biering-Sørensen[SUP] 1 2 17 22 [/SUP]
Affiliations
- PMID: 40888720
- DOI: 10.1056/NEJMoa2509907
Background: High-dose inactivated influenza vaccine has been shown to provide protection against influenza that is superior to that with the standard dose. However, data from individually randomized trials on the effectiveness of the high-dose vaccine against severe outcomes are limited.
Methods: In this pragmatic, open-label, randomized, controlled trial conducted in Denmark during the 2022-2023, 2023-2024, and 2024-2025 influenza seasons, we assigned older adults (≥65 years of age) to receive the high dose of the inactivated influenza vaccine or the standard dose. Data collection relied on nationwide administrative health registries. The primary end point was hospitalization for influenza or pneumonia that occurred from 14 days after vaccination through May 31 of the following year.
Results: Of the 332,438 participants who underwent randomization, 166,218 were assigned to receive the high-dose vaccine and 166,220 to receive the standard-dose vaccine. The mean (±SD) age of the participants was 73.7±5.8 years, and 161,538 participants (48.6%) were women. A primary end-point event occurred in 1138 participants (0.68%) in the high-dose group and in 1210 (0.73%) in the standard-dose group (relative vaccine effectiveness, 5.9%; 95.2% confidence interval [CI], -2.1 to 13.4; P = 0.14). Hospitalization for influenza occurred in 0.06% of the participants in the high-dose group and in 0.11% of those in the standard-dose group (relative vaccine effectiveness, 43.6%; 95.2% CI, 27.5 to 56.3); hospitalization for pneumonia occurred in 0.63% and 0.63%, respectively (relative effectiveness, 0.5%; 95.2% CI, -8.6 to 8.8); hospitalization for cardiorespiratory disease in 2.25% and 2.38% (relative effectiveness, 5.7%; 95.2% CI, 1.4 to 9.9); hospitalization for any cause in 9.38% and 9.58% (relative effectiveness, 2.1%; 95.2% CI, -0.1 to 4.3), and death from any cause in 0.67% and 0.66% (relative effectiveness, -2.5%; 95.2% CI, -11.6 to 5.9). The incidence of serious adverse events was similar in the two groups.
Conclusions: In this trial, a high-dose inactivated influenza vaccine did not result in a significantly lower incidence of hospitalization for influenza or pneumonia than a standard dose among older adults. (Funded by Sanofi; DANFLU-2 ClinicalTrials.gov number, NCT05517174; EU Clinical Trials Register number, 2022-500657-17-00.).