A real-world study evaluating the relative vaccine effectiveness of a cell-based quadrivalent influenza vaccine compared to egg-based quadrivalent influenza vaccine in the US during the 2017–18 influenza season

Abstract Background: Mutations of the H3N2 vaccine strain during the egg-based vaccine manufacturing process seem to partly explain the suboptimal effectiveness of traditional seasonal influenza vaccine. Cell-based influenza vaccines avoid such egg-adaptation, thereby improving antigenic match and vaccine effectiveness. The objective of this study was to evaluate the public health and economic impact of a cell-based quadrivalent influenza vaccine (QIVc) in adult population (18-64 years) compared to the standard egg-based quadrivalent influenza vaccine (QIVe), in the US. Methods: The impact of QIVc over QIVe in terms of public health and costs outcomes was estimated using a dynamic SEIR transmission model. The model is age-structured and accounts for 4 circulating influenza strains (A/H1N1pdm9, A/H3N2, B(Victoria), and B(Yamagata)). It was calibrated on US attack rate and strain circulation for the influenza seasons 2013-2018. US specific absolute vaccine effectiveness for QIVe, specific hospitalization rate, mortality rate, Quality-Adjusted Life Years (QALYs) and costs were extracted from published literature. Relative vaccine effectiveness of QIVc over QIVe for subjects 18-64 years of age was obtained from a US retrospective cohort study. Robustness of the results was assessed in univariate and probabilistic sensitivity analyses.Results: Switching from QIVe to QIVc in the 18-64 year-old population may prevent 5.7 M symptomatic cases, 1.8 M outpatient visits; 50K hospitalizations and 5,453 deaths annually. The switch could save 128 K QALYs and US$ 845M in direct costs, resulting in a cost-saving alternative in a 3-year time horizon analysis. Probabilistic sensitivity analyses confirmed the robustness of the cost-saving result.Conclusions: The analysis shows that QIVc is expected to prevent a substantial number of hospitalizations and deaths, and would result in substantial savings in health care costs.

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A Real-World Clinical and Economic Analysis of Cell-derived Quadrivalent Influenza Vaccine Compared to Standard Egg-derived Quadrivalent Influenza Vaccines During the 2019-20 Influenza Season in the United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab604 ◽

2021 ◽

Author(s):

Victoria Divino ◽

Vamshi Ruthwik Anupindi ◽

Mitch DeKoven ◽

Joaquin Mould-Quevedo ◽

Stephen I Pelton ◽

...

Keyword(s):

High Risk ◽

Influenza Vaccine ◽

Influenza Season ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Vaccines ◽

Sensitivity Analyses ◽

Administrative Claims ◽

Adaptive Mutations ◽

Quadrivalent Influenza Vaccine

Abstract Background Cell-derived influenza vaccines are not subject to egg adaptive mutations that have potential to decrease vaccine effectiveness. This retrospective analysis estimated the relative vaccine effectiveness (rVE) of cell-derived quadrivalent influenza vaccine (IIV4c) compared to standard egg-derived quadrivalent influenza vaccines (IIV4e) among recipients aged 4-64 years in the US during the 2019-20 influenza season. Methods The IQVIA PharMetrics® Plus administrative claims database was utilized. Study outcomes were assessed post-vaccination through the end of the study period (March 7, 2020). Inverse probability of treatment weighting (IPTW) was implemented to adjust for covariate imbalance. Adjusted rVE against influenza-related hospitalizations/emergency room (ER) visits and other clinical outcomes was estimated through IPTW-weighted Poisson regression models for the IIV4c and IIV4e cohorts and for the subgroup with ≥1 high-risk condition. Sensitivity analyses modifying the outcome assessment period as well as a doubly-robust analysis were also conducted. IPTW-weighted generalized linear models were used to estimate predicted annualized all-cause costs. Results The final sample comprised 1,138,969 IIV4c and 3,926,357 IIV4e recipients following IPTW adjustment. IIV4c was more effective in preventing influenza-related hospitalizations/ER visits as well as respiratory-related hospitalizations/ER visits compared to IIV4e. IIV4c was also more effective for the high-risk subgroup and across the sensitivity analyses. IIV4c was also associated with significantly lower annualized all-cause total costs compared to IIV4e (-$467), driven by lower costs for outpatient medical services and inpatient hospitalizations. Conclusions IIV4c was significantly more effective in preventing influenza-related hospitalizations/ER visits compared to IIV4e and was associated with significantly lower all-cause costs.

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1341. Relative Vaccine Effectiveness Against Influenza-related Hospitalizations and Respiratory Events During the 2019/20 Influenza seAson in U.S. Children and Adults. A Real-World Evidence Comparison Between Quadrivalent Cell-based and Egg-based Influenza Vaccines

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1533 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S758-S758

Author(s):

Stephen I Pelton ◽

Maarten Postma ◽

Victoria Divino ◽

Joaquin F Mould-Quevedo ◽

Ruthwik Anupindi ◽

...

Keyword(s):

High Risk ◽

Influenza Vaccine ◽

Influenza Season ◽

Standard Dose ◽

The United States ◽

Negative Control ◽

Vaccine Effectiveness ◽

Administrative Claims ◽

Real World Evidence ◽

Quadrivalent Influenza Vaccine

Abstract Background Non-egg-based influenza vaccine manufacturing reduces egg adaptation and therefore has the potential to increase vaccine effectiveness. This study evaluated whether the cell-based quadrivalent influenza vaccine (QIVc) improved relative vaccine effectiveness (rVE) compared to standard-dose egg-based quadrivalent influenza vaccine (QIVe-SD) in the reduction of influenza-related and respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season. Methods A retrospective analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the United States of America (U.S.) (IQVIA PharMetrics® Plus). Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders. Post-IPTW, the number of events and rates (per 1,000 vaccinated subject-seasons) of influenza-related hospitalizations/ER visits, respiratory-related hospitalizations/ER visits and all-cause hospitalizations were assessed. Poisson regression was used to estimate adjusted rVE. To avoid any influenza outcome misclassification with COVID-19 infection, the study period ended March 7,2020. A sub-analysis for a high-risk subgroup was conducted. Urinary tract infection (UTI) hospitalization was assessed as a negative control endpoint. Results During the 2019/20 influenza season, 1,150,134 QIVc and 3,924,819 QIVe-SD recipients were identified post-IPTW. Overall adjusted analyses (4-64 years old) found that QIVc was associated with a significantly higher rVE compared to QIVe-SD against influenza-related hospitalizations/ER visits (5.3% [95% CI: 0.5%-9.9%]), all-cause hospitalizations (14.5% [95% CI: 13.1%-15.8%]) and any respiratory-related hospitalization/ER visit (8.2% [95% CI: 6.5%-9.8%]). A similar trend was seen for the high-risk subgroup; for instance, rVE for QIVc compared to QIVe-SD against influenza-related hospitalizations/ER visits was 10.5% [95% CI: 2.9%-17.4%]. No effect was identified for the negative control outcome. Conclusion QIVc was significantly more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits, as well as all-cause hospitalizations, compared to QIVe-SD. Disclosures Stephen I. Pelton, MD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Victoria Divino, PhD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Ruthwik Anupindi, PhD, Seqirus (Consultant) Mitchell DeKoven, PhD, Seqirus (Consultant) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support)

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The Epidemiological and Economic Impact of a Cell-Based Quadrivalent Influenza Vaccine in Adults in the US: A Dynamic Modeling Approach

Vaccines ◽

10.3390/vaccines9101095 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1095

Author(s):

Van Hung Nguyen ◽

Yvonne Hilsky ◽

Joaquin Mould-Quevedo

Keyword(s):

Public Health ◽

Influenza Vaccine ◽

Economic Impact ◽

Influenza Vaccines ◽

Sensitivity Analyses ◽

Life Years ◽

The Us ◽

A Cell ◽

The Impact ◽

Quadrivalent Influenza Vaccine

Mutations of the H3N2 vaccine strain during the egg-based vaccine manufacturing process partly explain the suboptimal effectiveness of traditional seasonal influenza vaccines. Cell-based influenza vaccines improve antigenic match and vaccine effectiveness by avoiding such egg-adaptation. This study evaluated the public health and economic impact of a cell-based quadrivalent influenza vaccine (QIVc) in adults (18–64 years) compared to the standard egg-based quadrivalent influenza vaccine (QIVe) in the US. The impact of QIVc over QIVe in public health and cost outcomes was estimated using a dynamic age-structured SEIR transmission model, which accounted for four circulating influenza strains [A/H1N1pdm9, A/H3N2, B(Victoria), and B(Yamagata)] and was calibrated on the 2013–2018 influenza seasons. The robustness of the results was assessed in univariate and probabilistic sensitivity analyses. Switching from QIVe to QIVc in 18- to 64-year-olds may prevent 5.7 million symptomatic cases, 1.8 million outpatient visits, 50,000 hospitalizations, and 5453 deaths annually. The switch could save 128,000 Quality-Adjusted Life Years (QALYs) and US $ 845 M in direct costs, resulting in cost-savings in a three-year time horizon analysis. Probabilistic sensitivity analyses confirmed the robustness of the cost-saving result. The analysis shows that QIVc is expected to prevent hospitalizations and deaths, and result in substantial savings in healthcare costs.

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Effects of Influenza Vaccination in the United States During the 2018–2019 Influenza Season

Clinical Infectious Diseases ◽

10.1093/cid/ciz1244 ◽

2020 ◽

Vol 71 (8) ◽

pp. e368-e376 ◽

Cited By ~ 7

Author(s):

Jessie R Chung ◽

Melissa A Rolfes ◽

Brendan Flannery ◽

Pragati Prasad ◽

Alissa O’Halloran ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Influenza Season ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Monte Carlo Algorithm ◽

Medical Visits ◽

The Us

Abstract Background Multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018–2019 influenza season in the United States included prolonged circulation of A(H1N1)pdm09 viruses well-matched to the vaccine strain and A(H3N2) viruses, the majority of which were mismatched to the vaccine. We estimated the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season. Methods We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UIs) of influenza-associated outcomes prevented by vaccination in the United States. The model incorporated age-specific estimates of national 2018–2019 influenza vaccine coverage, influenza virus–specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network. Results Influenza vaccination prevented an estimated 4.4 million (95%UI, 3.4 million–7.1 million) illnesses, 2.3 million (95%UI, 1.8 million–3.8 million) medical visits, 58 000 (95%UI, 30 000–156 000) hospitalizations, and 3500 (95%UI, 1000–13 000) deaths due to influenza viruses during the US 2018–2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among children aged 6 months–4 years. Conclusions Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the United States, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated healthcare utilization even in a season in which a vaccine component does not match to a circulating virus.

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Vaccine effectiveness against influenza-associated hospitalizations among adults, 2018-2019, US Hospitalized Adult Influenza Vaccine Effectiveness Network

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa772 ◽

2020 ◽

Author(s):

J M Ferdinands ◽

M Gaglani ◽

S Ghamande ◽

E T Martin ◽

D Middleton ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza A ◽

Influenza Season ◽

Respiratory Illness ◽

Vaccine Effectiveness ◽

H3n2 Virus ◽

Influenza A H1n1 ◽

The Us ◽

Middle Aged Adults ◽

Residual Confounding

Abstract We estimated vaccine effectiveness for prevention of influenza-associated hospitalizations among adults during the 2018-2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network and testing positive for influenza were cases; patients testing negative were controls. Vaccine effectiveness was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09-associated hospitalization was 51% (95%CI 25, 68). Adjusted VE against influenza A(H3N2) virus-associated hospitalization was −2% (95%CI −65, 37) and differed significantly by age, with VE of −130% (95% CI −374, −27) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza-A(H1N1)pdm09-associated hospitalizations, it conferred no protection against influenza A(H3N2)-associated hospitalizations. We observed negative VE for young-and middle-aged adults but cannot exclude residual confounding as a potential explanation.

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Relative Effectiveness of the Cell-Derived Inactivated Quadrivalent Influenza Vaccine Versus Egg-Derived Inactivated Quadrivalent Influenza Vaccines in Preventing Influenza-Related Medical Encounters During the 2018-2019 Influenza Season in the United States

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1944 ◽

2021 ◽

Author(s):

Constantina Boikos ◽

Lauren Fischer ◽

Dan O’Brien ◽

Joe Vasey ◽

Gregg C Sylvester ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza Season ◽

Relative Effectiveness ◽

The United States ◽

Geographic Region ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Study Cohort ◽

Doubly Robust ◽

Quadrivalent Influenza Vaccine

Abstract Background The cell-propagated inactivated quadrivalent influenza vaccine (ccIIV4) may offer improved protection in seasons where egg-derived influenza viruses undergo mutations that affect antigenicity. This study estimated the relative vaccine effectiveness (rVE) of ccIIV4 versus egg-derived inactivated quadrivalent influenza vaccine (eIIV4) in preventing influenza-related medical encounters in the 2018-2019 U.S. season. Methods A dataset linking primary care electronic medical records with medical claims data was used to conduct a retrospective cohort study among individuals ≥4 years vaccinated with ccIIV4 or eIIV4 during the 2018-2019 season. Adjusted odds ratios (ORs) were derived from a doubly robust inverse probability of treatment-weighted approach adjusting for age, sex, race, ethnicity, geographic region, vaccination week, and health status. Relative vaccine effectiveness (rVE) was estimated by (1-OR)*100 and presented with 95% confidence intervals (CI). Results Following the application of inclusion/exclusion criteria, the study cohort included 2,125,430 ccIIV4 and 8,000,903 eIIV4 recipients. Adjusted analyses demonstrated a greater reduction in influenza-related medical encounters with ccIIV4 versus eIIV4, with the following rVE: overall, 7.6% (95% CI 6.5-8.6); age 4-17 years, 3.9% (0.9-7.0); 18-64 years, 6.5% (5.2-7.9); 18-49 years, 7.5% (5.7-9.3); 50-64 years, 5.6% (3.6-7.6); and ≥65 years, -2.2% (-5.4 to 0.9). Conclusions Adjusted analyses demonstrated statistically significantly greater reduction in influenza-related medical encounters in individuals vaccinated with ccIIV4 vs eIIV4 in the 2018-2019 U.S. influenza season. These results support ccIIV4 as a potentially more effective public health measure against influenza than an egg-based equivalent.

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Prediction of influenza vaccine effectiveness for the influenza season 2017/18 in the US

F1000Research ◽

10.12688/f1000research.13198.1 ◽

2017 ◽

Vol 6 ◽

pp. 2067 ◽

Cited By ~ 11

Author(s):

Slobodan Paessler ◽

Veljko Veljkovic

Keyword(s):

Influenza Vaccine ◽

Seasonal Influenza ◽

Influenza Season ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Antigenic Drift ◽

Correct Prediction ◽

Seasonal Influenza Vaccine ◽

The Us ◽

Key Factor

Vaccination against seasonal influenza viruses is the most effective way to prevent infection. A key factor in the effectiveness of the seasonal influenza vaccine is its immunological compatibility with the circulating viruses during the season. The high evolutionary rate, antigenic shift and antigenic drift of influenza viruses, represents the main obstacle for correct prediction of the vaccine effectiveness for an upcoming flu season. Conventional structural and phylogenetic approaches for assessment of vaccine effectiveness have had a limited success in prediction of vaccine efficacy in the past. Recently, a novel bioinformatics approach for assessment of effectiveness of seasonal influenza vaccine was proposed. Here, this approach was used for prediction of the vaccine effectiveness for the influenza season 2017/18 in US.

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The epidemiological and economic impact of a cell-based quadrivalent influenza vaccine in an adult population in the US: a dynamic modeling approach

10.21203/rs.3.rs-27872/v1 ◽

2020 ◽

Author(s):

Van Hung Nguyen ◽

Yvonne Hilsky ◽

Joaquin Mould-Quevedo

Keyword(s):

Public Health ◽

Cost Saving ◽

Influenza Vaccine ◽

Economic Impact ◽

Adult Population ◽

Vaccine Effectiveness ◽

Transmission Model ◽

Life Years ◽

A Cell ◽

Quadrivalent Influenza Vaccine

Abstract BackgroundMutations of the H3N2 vaccine strain during the egg-based vaccine manufacturing process seem to partly explain the suboptimal effectiveness of traditional seasonal influenza vaccine. Cell-based influenza vaccines avoid such egg-adaptation, thereby improving antigenic match and vaccine effectiveness. The objective of this study was to evaluate the public health and economic impact of a cell-based quadrivalent influenza vaccine (QIVc) in adult population (18–64 years) compared to the standard egg-based quadrivalent influenza vaccine (QIVe), in the US.MethodsThe impact of QIVc over QIVe in terms of public health and costs outcomes was estimated using a dynamic SEIR transmission model. The model is age-structured and accounts for 4 circulating influenza strains (A/H1N1pdm9, A/H3N2, B(Victoria), and B(Yamagata)). It was calibrated on US attack rate and strain circulation for the seasons 2013–2018. US specific absolute vaccine effectiveness for QIVe, specific hospitalization rate, mortality rate, Quality-Adjusted Life Years (QALYs) and costs were extracted from published literature. Relative vaccine effectiveness of QIVc over QIVe for subjects 18–64 years of age was obtained from a US retrospective cohort study. Robustness of the results was assessed in univariate and probabilistic sensitivity analyses.ResultsSwitching from QIVe to QIVc in the 18–64 year-old population may prevent 5.7 M symptomatic cases, 1.8 M outpatient visits; 50K hospitalizations and 5,453 deaths annually. The switch could save 128 K QALYs and US$ 845M in direct costs, resulting in a cost-saving alternative in a 3-year time horizon analysis. Probabilistic sensitivity analyses confirmed the robustness of the cost-saving result.ConclusionsThe analysis shows that QIVc is expected to prevent a substantial number of hospitalizations and deaths, and would result in substantial savings in health care costs.

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