DANFLU-1 was an open-label, active-controlled, individually randomized trial conducted in Denmark during the 2021/2022 northern hemisphere influenza season. Dr Niklas Dyrby Johansen (University of Copenhagen Copenhagen, Denmark) discusses the post-hoc analysis from DANFLU-1 which investigated the effects of high-dose quadrivalent influenza vaccine (QIV-HD) vs standard-dose quadrivalent influenza vaccine (QIV-SD).
The abstract ‘Relative effectiveness of high-dose vs standard-dose quadrivalent influenza vaccine in relation to influenza circulation: an analysis from the DANFLU-1 trial.’ (Abstract number: O0424) was presented at ECCMID 2023, 15-18 April, 2023, Copenhagen, Denmark.
Questions
- What is the prognosis of influenza and what are the challenges associated with optimizing vaccine efficacy and reducing the burden of disease? (0:21)
- Could you give a brief overview of the DANFLU-1 trial? (1:10)
- What are the aims, design and eligibility criteria of the post hoc analysis? (1:39)
- What were the key findings, and what are the implications for clinical practice? (3:05)
- How do the results of this post-hoc analysis compare to previous studies examining the efficacy of high-dose influenza vaccines? (4:11)
- What questions remain unanswered and what future studies are planned? (4:56)
Disclosures: Niklas Dyrby Johansen has nothing to disclose in relation to this video interview.
Support: Interview and filming supported by Touch Medical Media Ltd. Interview conducted by Katey Gabrysch and Victoria Jones.
Filmed in coverage of the 33rd European Congress of Clinical Microbiology & Infectious Diseases.
Click here for more content on viral infections & for further ECCMID 2023 highlights visit here.
Transcript
I’m Niklas Dyrby Johansen, and I’m a Medical Doctor at the University Hospital here in Copenhagen at the Atkins after hospital, and I’m a PhD student right now doing a lot of research in pragmatic trials, including influenza vaccines.
What is the prognosis of influenza and what are the challenges associated with optimizing vaccine efficacy and reducing the burden of disease? (0:21)
Influenza is a global health issue, affects approximately 1 billion people worldwide every season and causes an excess of 500,000 excess deaths each season. The challenges in making influenza vaccines is, of course, the antigenic drift and the difficulty in predicting which strain will be dominant in the particular season, and also especially in older adults and in immunocompromised individuals, we often see an insignificant antibody response towards the vaccines, and that’s why, among other things, that the high dose vaccine was developed initially.
Could you give a brief overview of the DANFLU-1 trial? (1:10)
DANFLU-1 trial was a pragmatic, open register based randomized trial conducted during the 2021 2022 influenza season. It randomized almost 12,500 Danish citizens aged 65 to 79 years to high dose or standard dose quadrivalent influenza vaccine in a 1 to 1 ratio and followed them for clinical outcomes for that particular influenza season.
What are the aims, design and eligibility criteria of the post hoc analysis? (1:39)
The main question of Fame for one was actually, is it feasible to conduct lasting pragmatic studies using registries and integrating trials into routine vaccination practice? We found that it was definitely feasible, and then the main results were also that we found that high dose quadrivalent influenza vaccine reduce the incidence of influenza and pneumonia, hospitalization and all cause death. In this post hoc analysis, we tried to look at how the effectiveness of the different vaccines varied according to influence of circulation levels. We included all 12,500 participants in this post-hoc analysis, and did a recurrent events analysis considering the total number of outcome events, not just the first event as has traditionally been done. We found Additionally that when considering recurrent events, we saw a significant reduction in all cause hospitalization, and for the outcomes which were reduced we found that the trends were observed prior to influenza circulation starting to rise in Denmark. We had a late peak in that particular season where the study was conducted in around March to April, but we could already see effectiveness prior to that peak in favour of the high dose vaccine.
What were the key findings, and what are the implications for clinical practice? (3:05)
This analysis is exploratory, but of course, it’s interesting to see that there may be unspecific effects of influenza vaccines, as has been known from other vaccine types, mostly live vaccines, tuberculosis and so on, that have specific effects. But maybe there may also be immunomodulatory effects of different types of influenza vaccines that can explain this, and that’s, of course, a topic for further research. Of course, influenza vaccination remains widely recommended, regardless of which type of influenza vaccine, you would have in your particular country. We feel that the trial we conducted shows the path towards conducting randomized post-approval trials, maybe not relying so much on observational data, but maybe try to integrate randomization into routine practice. When there are two treatments that could be equivalent, why not randomize and follow patients through the registries that you have in many countries now, not just in my country (Denmark) as well?
How do the results of this post-hoc analysis compare to previous studies examining the efficacy of high-dose influenza vaccines? (4:11)
There have been previous randomized trials of trivalent influenza vaccines that have also shown reductions in all cause hospitalization. Just like we found, no previous studies that have investigated the quadrivalent high dose vaccine, and of course, these are all post-hoc analysis. It’s not the primary outcome of the study, but we are now conducting the DANFLU-2 to study actually, which will be an even larger trial than the 10 to 1 trial, which was underpowered despite having 12,500 participants. So we will conduct that and probably be able to fully conclude on some of these endpoints.
What questions remain unanswered and what future studies are planned? (4:56)
I think we have to have a deeper understanding of the potential mechanism behind these on specific effects that we saw. We have some studies from atherosclerosis, where we can see different cytokines being up and downregulated, but I think there needs to be a deep understanding of potential and specific effects of vaccines.
Subtitles and transcript are autogenerated.
