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According to a pair of studies published online Oct. 29 in the Journal of Infectious Diseases, statins – a class of drugs widely utilized by older adults to reduce cholesterol – may have the unintended consequence of reducing immunotherapeutic response to and effectiveness of influenza vaccination.
In a post-hoc analysis (J Infect Dis. 2015 Oct 29. doi: 10.1093/infdis/jiv456), Dr. Steven Black of Cincinnati Children’s Hospital Medical Center and colleagues derived data from an international, multisite, randomized, controlled, influenza vaccine clinical trial population of 6,961 subjects over the age of 65. At 3 weeks post vaccination, the researchers measured the level of antibodies to flu vaccine strains in the blood of both statin and non–statin taking participants. The investigators discovered that hemagglutination-inhibiting geometric mean titers to influenza A (H1NI), A (H3N2), and B strains were 38% (95% confidence interval, 27%-50%), 67% (95% CI, 54%-80%) and 38% (95% CI, 28%-29%) lower, respectively, in the statin therapy arm as compared with the non–statin therapy cohort. The effect was most dramatic in patients on synthetic (as opposed to natural, fermentation-derived) statin treatment regimens.
“Apparently, statins interfere with the response to influenza vaccine and lower the immune response, and this would seem to also result in a lower effectiveness of influenza vaccines,” Dr. Black and his colleagues wrote. Potential mitigation strategies for statin-induced immunosuppression suggested by the research team include preferential use of high-dose or adjuvanted vaccines.
In addition, a separate retrospective investigation (J Infect Dis. 2015 Oct 29. doi: 10.1093/infdis/jiv457.) tracking 137,488 patients from a Georgia managed care organization database over nine flu seasons (from 2002 to 2011) also generated data implying a connection between statin use and compromised influenza vaccine efficacy and immune response. Dr. Saad Omer of the Emory Vaccine Center at Emory University in Atlanta and his colleagues analyzed the impact of statins on influenza vaccine efficacy against medically attended acute respiratory illness (MAARI). MAARI incidence is routinely employed as an influenza impact marker, although not all MAARI incidence is influenza related.
The Emory University research team found that influenza vaccine effectiveness against MAARI was decreased in statin users, compared with nonusers during periods of local (14.1% vs. 22.9%; mean difference, 11.4%; 95% CI, −1.7%-26.1%) and widespread (12.6% vs. 26.2%; mean difference, 18.4%; 95% CI, 2.9%-36.2%) influenza circulation. “Even after adjustment for several covariates … the observed reduction in influenza vaccine effectiveness among statin users remained statistically significant for periods of widespread influenza circulation with a nonsignificant trend toward reduced vaccine effectiveness during periods of local circulation, as well,” noted Dr. Omer and his coauthors. Said results, wrote the researchers, “have potential implications for clinical guidelines regarding statin use around the time of routine vaccinations.”
Dr. Black is a consultant for Novartis Vaccines, GSK, Takeda Vaccines, Protein Sciences, and the World Health Organization. His coauthors – Dr. Uwe Nicolay, Dr. Giuseppe Del Giudice, and Dr. Rino Rappuoli – are employees of Novartis Vaccines.
Novartis Vaccines funded the post-hoc analysis conducted by Dr. Black and his colleagues, as well as the original clinical trial that developed the data utilized for the analysis. Dr. Omer and his colleagues were funded by Emory University and the National Institute of Allergy and Infectious Diseases and reported no relevant disclosures.
The findings that statin use adversely affects IIV (inactivated influenza vaccine) immunogenicity and vaccine effectiveness are biologically plausible, based on known immunomodulatory effects of these drugs and raise important questions about the use of these important medications. Should these results affect a physician’s care of patients? Should statins be stopped for a period while influenza vaccine is administered? Should IIV not be administered to statin users? The answer to all of these questions is no.
Instead the results of these studies should be viewed as hypothesis generating and should prompt further investigation. If statins are found to reduce immunogenicity, then potentially transient interruption of statin therapy could be considered for testing. The effect of chronic statin use on the immunogenicity of other vaccines also needs to be evaluated further. Future studies could also evaluate whether alternative vaccination strategies with improved immunogenicity, such as high-dose, intradermally delivered, or adjuvanted vaccines will overcome the effects of statin use (if any).
The results also underscore the need for the development of influenza vaccines with improved efficacy and effectiveness.
Dr. Robert L. Atmar is a professor of medicine and interim chief of medicine-infectious disease at the Baylor College of Medicine, Houston, Texas. Dr. Wendy A. Keitel is an associate professor of molecular virology and microbiology at the Baylor College of Medicine, Houston, Texas. Dr. Atmar reported receiving grants from Takeda Vaccines. Dr. Keitel reported no relevant disclosures. Dr. Atmar and Dr. Keitel made these remarks in an editorial commentary (J Infect Dis. 2015 Oct 29. doi: 10.1093/infdis/jiv459.) that accompanied the data furnished by Dr. Black and colleagues and Dr. Omer and colleagues.
The findings that statin use adversely affects IIV (inactivated influenza vaccine) immunogenicity and vaccine effectiveness are biologically plausible, based on known immunomodulatory effects of these drugs and raise important questions about the use of these important medications. Should these results affect a physician’s care of patients? Should statins be stopped for a period while influenza vaccine is administered? Should IIV not be administered to statin users? The answer to all of these questions is no.
Instead the results of these studies should be viewed as hypothesis generating and should prompt further investigation. If statins are found to reduce immunogenicity, then potentially transient interruption of statin therapy could be considered for testing. The effect of chronic statin use on the immunogenicity of other vaccines also needs to be evaluated further. Future studies could also evaluate whether alternative vaccination strategies with improved immunogenicity, such as high-dose, intradermally delivered, or adjuvanted vaccines will overcome the effects of statin use (if any).
The results also underscore the need for the development of influenza vaccines with improved efficacy and effectiveness.
Dr. Robert L. Atmar is a professor of medicine and interim chief of medicine-infectious disease at the Baylor College of Medicine, Houston, Texas. Dr. Wendy A. Keitel is an associate professor of molecular virology and microbiology at the Baylor College of Medicine, Houston, Texas. Dr. Atmar reported receiving grants from Takeda Vaccines. Dr. Keitel reported no relevant disclosures. Dr. Atmar and Dr. Keitel made these remarks in an editorial commentary (J Infect Dis. 2015 Oct 29. doi: 10.1093/infdis/jiv459.) that accompanied the data furnished by Dr. Black and colleagues and Dr. Omer and colleagues.
The findings that statin use adversely affects IIV (inactivated influenza vaccine) immunogenicity and vaccine effectiveness are biologically plausible, based on known immunomodulatory effects of these drugs and raise important questions about the use of these important medications. Should these results affect a physician’s care of patients? Should statins be stopped for a period while influenza vaccine is administered? Should IIV not be administered to statin users? The answer to all of these questions is no.
Instead the results of these studies should be viewed as hypothesis generating and should prompt further investigation. If statins are found to reduce immunogenicity, then potentially transient interruption of statin therapy could be considered for testing. The effect of chronic statin use on the immunogenicity of other vaccines also needs to be evaluated further. Future studies could also evaluate whether alternative vaccination strategies with improved immunogenicity, such as high-dose, intradermally delivered, or adjuvanted vaccines will overcome the effects of statin use (if any).
The results also underscore the need for the development of influenza vaccines with improved efficacy and effectiveness.
Dr. Robert L. Atmar is a professor of medicine and interim chief of medicine-infectious disease at the Baylor College of Medicine, Houston, Texas. Dr. Wendy A. Keitel is an associate professor of molecular virology and microbiology at the Baylor College of Medicine, Houston, Texas. Dr. Atmar reported receiving grants from Takeda Vaccines. Dr. Keitel reported no relevant disclosures. Dr. Atmar and Dr. Keitel made these remarks in an editorial commentary (J Infect Dis. 2015 Oct 29. doi: 10.1093/infdis/jiv459.) that accompanied the data furnished by Dr. Black and colleagues and Dr. Omer and colleagues.
According to a pair of studies published online Oct. 29 in the Journal of Infectious Diseases, statins – a class of drugs widely utilized by older adults to reduce cholesterol – may have the unintended consequence of reducing immunotherapeutic response to and effectiveness of influenza vaccination.
In a post-hoc analysis (J Infect Dis. 2015 Oct 29. doi: 10.1093/infdis/jiv456), Dr. Steven Black of Cincinnati Children’s Hospital Medical Center and colleagues derived data from an international, multisite, randomized, controlled, influenza vaccine clinical trial population of 6,961 subjects over the age of 65. At 3 weeks post vaccination, the researchers measured the level of antibodies to flu vaccine strains in the blood of both statin and non–statin taking participants. The investigators discovered that hemagglutination-inhibiting geometric mean titers to influenza A (H1NI), A (H3N2), and B strains were 38% (95% confidence interval, 27%-50%), 67% (95% CI, 54%-80%) and 38% (95% CI, 28%-29%) lower, respectively, in the statin therapy arm as compared with the non–statin therapy cohort. The effect was most dramatic in patients on synthetic (as opposed to natural, fermentation-derived) statin treatment regimens.
“Apparently, statins interfere with the response to influenza vaccine and lower the immune response, and this would seem to also result in a lower effectiveness of influenza vaccines,” Dr. Black and his colleagues wrote. Potential mitigation strategies for statin-induced immunosuppression suggested by the research team include preferential use of high-dose or adjuvanted vaccines.
In addition, a separate retrospective investigation (J Infect Dis. 2015 Oct 29. doi: 10.1093/infdis/jiv457.) tracking 137,488 patients from a Georgia managed care organization database over nine flu seasons (from 2002 to 2011) also generated data implying a connection between statin use and compromised influenza vaccine efficacy and immune response. Dr. Saad Omer of the Emory Vaccine Center at Emory University in Atlanta and his colleagues analyzed the impact of statins on influenza vaccine efficacy against medically attended acute respiratory illness (MAARI). MAARI incidence is routinely employed as an influenza impact marker, although not all MAARI incidence is influenza related.
The Emory University research team found that influenza vaccine effectiveness against MAARI was decreased in statin users, compared with nonusers during periods of local (14.1% vs. 22.9%; mean difference, 11.4%; 95% CI, −1.7%-26.1%) and widespread (12.6% vs. 26.2%; mean difference, 18.4%; 95% CI, 2.9%-36.2%) influenza circulation. “Even after adjustment for several covariates … the observed reduction in influenza vaccine effectiveness among statin users remained statistically significant for periods of widespread influenza circulation with a nonsignificant trend toward reduced vaccine effectiveness during periods of local circulation, as well,” noted Dr. Omer and his coauthors. Said results, wrote the researchers, “have potential implications for clinical guidelines regarding statin use around the time of routine vaccinations.”
Dr. Black is a consultant for Novartis Vaccines, GSK, Takeda Vaccines, Protein Sciences, and the World Health Organization. His coauthors – Dr. Uwe Nicolay, Dr. Giuseppe Del Giudice, and Dr. Rino Rappuoli – are employees of Novartis Vaccines.
Novartis Vaccines funded the post-hoc analysis conducted by Dr. Black and his colleagues, as well as the original clinical trial that developed the data utilized for the analysis. Dr. Omer and his colleagues were funded by Emory University and the National Institute of Allergy and Infectious Diseases and reported no relevant disclosures.
According to a pair of studies published online Oct. 29 in the Journal of Infectious Diseases, statins – a class of drugs widely utilized by older adults to reduce cholesterol – may have the unintended consequence of reducing immunotherapeutic response to and effectiveness of influenza vaccination.
In a post-hoc analysis (J Infect Dis. 2015 Oct 29. doi: 10.1093/infdis/jiv456), Dr. Steven Black of Cincinnati Children’s Hospital Medical Center and colleagues derived data from an international, multisite, randomized, controlled, influenza vaccine clinical trial population of 6,961 subjects over the age of 65. At 3 weeks post vaccination, the researchers measured the level of antibodies to flu vaccine strains in the blood of both statin and non–statin taking participants. The investigators discovered that hemagglutination-inhibiting geometric mean titers to influenza A (H1NI), A (H3N2), and B strains were 38% (95% confidence interval, 27%-50%), 67% (95% CI, 54%-80%) and 38% (95% CI, 28%-29%) lower, respectively, in the statin therapy arm as compared with the non–statin therapy cohort. The effect was most dramatic in patients on synthetic (as opposed to natural, fermentation-derived) statin treatment regimens.
“Apparently, statins interfere with the response to influenza vaccine and lower the immune response, and this would seem to also result in a lower effectiveness of influenza vaccines,” Dr. Black and his colleagues wrote. Potential mitigation strategies for statin-induced immunosuppression suggested by the research team include preferential use of high-dose or adjuvanted vaccines.
In addition, a separate retrospective investigation (J Infect Dis. 2015 Oct 29. doi: 10.1093/infdis/jiv457.) tracking 137,488 patients from a Georgia managed care organization database over nine flu seasons (from 2002 to 2011) also generated data implying a connection between statin use and compromised influenza vaccine efficacy and immune response. Dr. Saad Omer of the Emory Vaccine Center at Emory University in Atlanta and his colleagues analyzed the impact of statins on influenza vaccine efficacy against medically attended acute respiratory illness (MAARI). MAARI incidence is routinely employed as an influenza impact marker, although not all MAARI incidence is influenza related.
The Emory University research team found that influenza vaccine effectiveness against MAARI was decreased in statin users, compared with nonusers during periods of local (14.1% vs. 22.9%; mean difference, 11.4%; 95% CI, −1.7%-26.1%) and widespread (12.6% vs. 26.2%; mean difference, 18.4%; 95% CI, 2.9%-36.2%) influenza circulation. “Even after adjustment for several covariates … the observed reduction in influenza vaccine effectiveness among statin users remained statistically significant for periods of widespread influenza circulation with a nonsignificant trend toward reduced vaccine effectiveness during periods of local circulation, as well,” noted Dr. Omer and his coauthors. Said results, wrote the researchers, “have potential implications for clinical guidelines regarding statin use around the time of routine vaccinations.”
Dr. Black is a consultant for Novartis Vaccines, GSK, Takeda Vaccines, Protein Sciences, and the World Health Organization. His coauthors – Dr. Uwe Nicolay, Dr. Giuseppe Del Giudice, and Dr. Rino Rappuoli – are employees of Novartis Vaccines.
Novartis Vaccines funded the post-hoc analysis conducted by Dr. Black and his colleagues, as well as the original clinical trial that developed the data utilized for the analysis. Dr. Omer and his colleagues were funded by Emory University and the National Institute of Allergy and Infectious Diseases and reported no relevant disclosures.
FROM THE JOURNAL OF INFECTIOUS DISEASES
Key clinical point: Statin therapy may adversely impact the efficacy of influenza vaccine.
Major findings: Hemagglutination-inhibiting geometric mean titers to influenza A (H1NI), A (H3N2), and B strains were 38% , 67%, and 38% lower, respectively, in the chronic statin therapy cohort (compared with the non–statin therapy group). Influenza vaccine effectiveness against acute respiratory illness was decreased in statin users, compared with nonusers during periods of local and widespread influenza circulation.
Data source: A retrospective analysis of 6,961 subjects over the age of 65 from a randomized, controlled influenza vaccine trial; a retrospective cohort study of 137,488 Georgia managed care patients over nine flu seasons from 2002/2003 to 2010/2011 (totaling 447,588 person-seasons).
Disclosures: Dr. Steven Black is a consultant for Novartis Vaccines, GSK, Takeda Vaccines, Protein Sciences, and the World Health Organization. His coauthors – Dr. Uwe Nicolay, Dr. Giuseppe Del Giudice, and Dr. Rino Rappuoli – are employees of Novartis Vaccines. Novartis Vaccines funded the post-hoc analysis conducted by Dr. Black and colleagues and also the original clinical trial that developed the data utilized for said analysis.
Dr. Saad Omer and colleagues were funded by Emory University and the National Institute of Allergy and Infectious Diseases and reported no relevant disclosures.
