tetano
Editor, Senior Moderator
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. 2025 Oct 17:S0140-6736(25)01742-8.
doi: 10.1016/S0140-6736(25)01742-8. Online ahead of print. Effectiveness of high-dose influenza vaccine against hospitalisations in older adults (FLUNITY-HD): an individual-level pooled analysis
Niklas Dyrby Johansen[SUP] 1 [/SUP], Daniel Modin[SUP] 1 [/SUP], Jacobo Pardo-Seco[SUP] 2 [/SUP], Carmen Rodriguez-Tenreiro-Sánchez[SUP] 3 [/SUP], Matthew M Loiacono[SUP] 4 [/SUP], Rebecca C Harris[SUP] 5 [/SUP], Marine Dufournet[SUP] 6 [/SUP], Robertus van Aalst[SUP] 7 [/SUP], Ayman Chit[SUP] 8 [/SUP], Carsten Schade Larsen[SUP] 9 [/SUP], Lykke Larsen[SUP] 10 [/SUP], Lothar Wiese[SUP] 11 [/SUP], Michael Dalager-Pedersen[SUP] 12 [/SUP], Brian L Claggett[SUP] 13 [/SUP], Kira Hyldekær Janstrup[SUP] 1 [/SUP], Carmen Duran-Parrondo[SUP] 14 [/SUP], Marta Piñeiro-Sotelo[SUP] 14 [/SUP], Martín Cribeiro-González[SUP] 15 [/SUP], Mónica Conde-Pájaro[SUP] 14 [/SUP], Susana Mirás-Carballal[SUP] 14 [/SUP], Juan-Manuel González-Pérez[SUP] 16 [/SUP], Scott D Solomon[SUP] 13 [/SUP], Pradeesh Sivapalan[SUP] 17 [/SUP], Cyril Jean-Marie Martel[SUP] 18 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 17 [/SUP], Federico Martinón-Torres[SUP] 3 [/SUP], Tor Biering-Sørensen[SUP] 19 [/SUP]; DANFLU-2 Study Group; GALFLU Trial Team
Collaborators, Affiliations
Background: Two large-scale trials comparing high-dose inactivated influenza vaccine (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) against hospitalisation outcomes have been conducted in Denmark and Spain. We aimed to analyse the pooled data from these trials to enhance generalisability and assess the relative vaccine effectiveness (rVE) of HD-IIV versus SD-IIV against severe clinical outcomes in older adults.
Methods: FLUNITY-HD was a prespecified, individual-level pooled analysis of two methodologically harmonised pragmatic, individually randomised trials comparing HD-IIV with SD-IIV in older adults. DANFLU-2 included adults aged 65 years or older and GALFLU included community-dwelling adults aged 65-79 years. DANFLU-2 was conducted during the 2022-23, 2023-24, and 2024-25 influenza seasons in Denmark, whereas GALFLU was conducted during the 2023-24 and 2024-25 seasons in Galicia, Spain. In both trials, participants were randomly assigned (1:1) to receive either HD-IIV (60 μg of haemagglutinin [HA] antigen per strain) or SD-IIV (15 μg of HA antigen per strain) and followed up for the occurrence of endpoints from 14 days after vaccination to May 31 the following year in each season. Routine health-care databases were used as primary data source. The primary endpoint of both the pooled analysis and the individual trials was hospitalisation for influenza or pneumonia. Secondary endpoints were tested hierarchically, and consisted of hospitalisation for any cardiorespiratory disease, laboratory-confirmed influenza hospitalisation, all-cause hospitalisation, all-cause mortality, hospitalisation for influenza (ICD-10), and hospitalisation for pneumonia. The pooled analysis is registered with ClinicalTrials.gov, NCT06506812.
Findings: The analysis included 466 320 individually randomised participants (233 311 were randomly assigned to HD-IIV and 233 009 to SD-IIV). Mean age was 73·3 years (SD 5·4); 223 681 (48·0%) were female and 242 639 (52·0%) were male. 228 125 (48·9%) participants had at least one chronic condition. The primary endpoint of hospitalisation for influenza or pneumonia occurred in 1312 (0·56%) of 233 311 participants in the HD-IIV group compared with 1437 (0·62%) of 233 009 participants in the SD-IIV group (rVE 8·8%, 95% CI 1·7 to 15·5; one-sided p=0·0082). HD-IIV also reduced the incidence of cardiorespiratory hospitalisation (4720 [2·02%] participants in the HD-IIV group vs 5033 [2·16%] participants in the SD-IIV group; rVE 6·3%, 2·5 to 10·0; p=0·0006), laboratory-confirmed influenza hospitalisation (249 [0·11%] participants vs 365 [0·16%] participants; rVE 31·9%, 19·7 to 42·2; p<0·0001), and all-cause hospitalisation (19 921 [8·54%] vs 20 348 [8·73%]; rVE 2·2%, 0·3 to 4·1; p=0·012). All-cause mortality occurred with similar frequency in both groups (1421 [0·61%] vs 1437 [0·62%]; rVE 1·2%, -6·3 to 8·3; p=0·38). ICD-10-coded hospitalisation for influenza occurred in 164 (0·07%) participants in the HD-IIV group and 271 (0·12%) participants in the SD-IIV group (rVE 39·6%, 26·4 to 50·5) and hospitalisation for pneumonia occurred in 1161 (0·50%) participants in the HD-IIV group and 1187 (0·51%) participants in the SD-IIV group (rVE 2·3%, -6·0 to 10·0). The incidence of serious adverse events was similar between groups (16 032 events in the HD-IIV group and 15 857 events in the SD-IIV group).
Interpretation: In this prespecified pooled analysis, HD-IIV demonstrated superior protection compared with SD-IIV against hospitalisation for influenza or pneumonia and also reduced the incidence of the secondary endpoints of cardiorespiratory hospitalisation, laboratory-confirmed influenza hospitalisation, and all-cause hospitalisation. Given wide eligibility for influenza vaccination, implementing HD-IIV could result in substantial public health benefits.
Funding: Sanofi.
. 2025 Oct 17:S0140-6736(25)01742-8.
doi: 10.1016/S0140-6736(25)01742-8. Online ahead of print. Effectiveness of high-dose influenza vaccine against hospitalisations in older adults (FLUNITY-HD): an individual-level pooled analysis
Niklas Dyrby Johansen[SUP] 1 [/SUP], Daniel Modin[SUP] 1 [/SUP], Jacobo Pardo-Seco[SUP] 2 [/SUP], Carmen Rodriguez-Tenreiro-Sánchez[SUP] 3 [/SUP], Matthew M Loiacono[SUP] 4 [/SUP], Rebecca C Harris[SUP] 5 [/SUP], Marine Dufournet[SUP] 6 [/SUP], Robertus van Aalst[SUP] 7 [/SUP], Ayman Chit[SUP] 8 [/SUP], Carsten Schade Larsen[SUP] 9 [/SUP], Lykke Larsen[SUP] 10 [/SUP], Lothar Wiese[SUP] 11 [/SUP], Michael Dalager-Pedersen[SUP] 12 [/SUP], Brian L Claggett[SUP] 13 [/SUP], Kira Hyldekær Janstrup[SUP] 1 [/SUP], Carmen Duran-Parrondo[SUP] 14 [/SUP], Marta Piñeiro-Sotelo[SUP] 14 [/SUP], Martín Cribeiro-González[SUP] 15 [/SUP], Mónica Conde-Pájaro[SUP] 14 [/SUP], Susana Mirás-Carballal[SUP] 14 [/SUP], Juan-Manuel González-Pérez[SUP] 16 [/SUP], Scott D Solomon[SUP] 13 [/SUP], Pradeesh Sivapalan[SUP] 17 [/SUP], Cyril Jean-Marie Martel[SUP] 18 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 17 [/SUP], Federico Martinón-Torres[SUP] 3 [/SUP], Tor Biering-Sørensen[SUP] 19 [/SUP]; DANFLU-2 Study Group; GALFLU Trial Team
Collaborators, Affiliations
- PMID: 41115437
- DOI: 10.1016/S0140-6736(25)01742-8
Background: Two large-scale trials comparing high-dose inactivated influenza vaccine (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) against hospitalisation outcomes have been conducted in Denmark and Spain. We aimed to analyse the pooled data from these trials to enhance generalisability and assess the relative vaccine effectiveness (rVE) of HD-IIV versus SD-IIV against severe clinical outcomes in older adults.
Methods: FLUNITY-HD was a prespecified, individual-level pooled analysis of two methodologically harmonised pragmatic, individually randomised trials comparing HD-IIV with SD-IIV in older adults. DANFLU-2 included adults aged 65 years or older and GALFLU included community-dwelling adults aged 65-79 years. DANFLU-2 was conducted during the 2022-23, 2023-24, and 2024-25 influenza seasons in Denmark, whereas GALFLU was conducted during the 2023-24 and 2024-25 seasons in Galicia, Spain. In both trials, participants were randomly assigned (1:1) to receive either HD-IIV (60 μg of haemagglutinin [HA] antigen per strain) or SD-IIV (15 μg of HA antigen per strain) and followed up for the occurrence of endpoints from 14 days after vaccination to May 31 the following year in each season. Routine health-care databases were used as primary data source. The primary endpoint of both the pooled analysis and the individual trials was hospitalisation for influenza or pneumonia. Secondary endpoints were tested hierarchically, and consisted of hospitalisation for any cardiorespiratory disease, laboratory-confirmed influenza hospitalisation, all-cause hospitalisation, all-cause mortality, hospitalisation for influenza (ICD-10), and hospitalisation for pneumonia. The pooled analysis is registered with ClinicalTrials.gov, NCT06506812.
Findings: The analysis included 466 320 individually randomised participants (233 311 were randomly assigned to HD-IIV and 233 009 to SD-IIV). Mean age was 73·3 years (SD 5·4); 223 681 (48·0%) were female and 242 639 (52·0%) were male. 228 125 (48·9%) participants had at least one chronic condition. The primary endpoint of hospitalisation for influenza or pneumonia occurred in 1312 (0·56%) of 233 311 participants in the HD-IIV group compared with 1437 (0·62%) of 233 009 participants in the SD-IIV group (rVE 8·8%, 95% CI 1·7 to 15·5; one-sided p=0·0082). HD-IIV also reduced the incidence of cardiorespiratory hospitalisation (4720 [2·02%] participants in the HD-IIV group vs 5033 [2·16%] participants in the SD-IIV group; rVE 6·3%, 2·5 to 10·0; p=0·0006), laboratory-confirmed influenza hospitalisation (249 [0·11%] participants vs 365 [0·16%] participants; rVE 31·9%, 19·7 to 42·2; p<0·0001), and all-cause hospitalisation (19 921 [8·54%] vs 20 348 [8·73%]; rVE 2·2%, 0·3 to 4·1; p=0·012). All-cause mortality occurred with similar frequency in both groups (1421 [0·61%] vs 1437 [0·62%]; rVE 1·2%, -6·3 to 8·3; p=0·38). ICD-10-coded hospitalisation for influenza occurred in 164 (0·07%) participants in the HD-IIV group and 271 (0·12%) participants in the SD-IIV group (rVE 39·6%, 26·4 to 50·5) and hospitalisation for pneumonia occurred in 1161 (0·50%) participants in the HD-IIV group and 1187 (0·51%) participants in the SD-IIV group (rVE 2·3%, -6·0 to 10·0). The incidence of serious adverse events was similar between groups (16 032 events in the HD-IIV group and 15 857 events in the SD-IIV group).
Interpretation: In this prespecified pooled analysis, HD-IIV demonstrated superior protection compared with SD-IIV against hospitalisation for influenza or pneumonia and also reduced the incidence of the secondary endpoints of cardiorespiratory hospitalisation, laboratory-confirmed influenza hospitalisation, and all-cause hospitalisation. Given wide eligibility for influenza vaccination, implementing HD-IIV could result in substantial public health benefits.
Funding: Sanofi.