scholarly journals Relative Effectiveness of Adjuvanted Trivalent Inactivated Influenza Vaccine Versus Egg-derived Quadrivalent Inactivated Influenza Vaccines and High-dose Trivalent Influenza Vaccine in Preventing Influenza-related Medical Encounters in US Adults ≥ 65 Years During the 2017–2018 and 2018–2019 Influenza Seasons

Author(s):  
Constantina Boikos ◽  
Lauren Fischer ◽  
Dan O’Brien ◽  
Joe Vasey ◽  
Gregg C Sylvester ◽  
...  

Abstract Background The effectiveness of standard, egg-derived quadrivalent influenza vaccines (IIV4) may be reduced in adults ≥65 years of age, largely because of immunosenescence. An MF59-adjuvanted trivalent influenza vaccine (aIIV3) and a high-dose trivalent influenza vaccine (HD-IIV3) offer older adults enhanced protection versus standard vaccines. This study compared the relative effectiveness of aIIV3 with IIV4 and HD-IIV3 in preventing influenza-related medical encounters over 2 US influenza seasons. Methods This retrospective cohort study included US patients ≥65 years vaccinated with aIIV3, IIV4, or HD-IIV3. The outcome of interest was the occurrence of influenza-related medical encounters. Data were derived from a large dataset comprising primary and specialty care electronic medical records linked with pharmacy and medical claims. Adjusted odds ratios (OR) were derived from an inverse probability of treatment-weighted sample adjusted for age, sex, race, ethnicity, geographic region, vaccination week, and health status. Relative vaccine effectiveness (rVE) was determined using the formula (% VE = 1 – ORadjusted) × 100. Results In 2017–2018, cohorts included: aIIV3, n = 524 223; IIV4, n = 917 609; and HD-IIV3, n = 3 377 860. After adjustment, 2017–2018 rVE of aIIV3 versus IIV4 was 18.2 (95% confidence interval [CI], 15.8–20.5); aIIV3 vs. HD-IIV3 was 7.7 (95% CI, 2.3–12.8). In 2018–2019, cohorts included: aIIV3, n = 1 031 145; IIV4, n = 915 380; HD-IIV3, n = 3 809 601, with adjusted rVEs of aIIV3 versus IIV4 of 27.8 (95% CI, 25.7–29.9) and vs. HD-IIV3 of 6.9 (95% CI, 3.1–10.6). Conclusion In the 2017–2018 and 2018–2019 influenza seasons in the United States, aIIV3 demonstrated greater reduction in influenza-related medical encounters than IIV4 and HD-IIV3 in adults ≥65 years.

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S136-S136
Author(s):  
myron J levin ◽  
Victoria Divino ◽  
Stephen I Pelton ◽  
Maarten Postma ◽  
Drishti Shah ◽  
...  

Abstract Background According to the Centers for Disease Control and Prevention (CDC), during the 2019-20 U.S. influenza season, influenza resulted in almost 180,000 hospitalizations and over 13,000 deaths in adults ≥ 65 years. The current study evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent influenza vaccine (aTIV) compared to high-dose trivalent influenza vaccine (TIV-HD), against influenza-related hospitalizations/emergency room (ER) visits, all-cause hospitalizations and hospitalizations/ER visits for cardio-respiratory disease (CRD) among adults ≥65 years for the 2019-20 influenza season. Methods A retrospective cohort analysis of older adults (≥ 65 years) was conducted using IQVIA’s professional fee, prescription claims and hospital charge master data in the U.S. Baseline characteristics included age, gender, payer type, geographic region, Charlson Comorbidity Index (CCI), comorbidities, indicators of frail health status, and pre-index hospitalization rates. To avoid any influenza outcome misclassification with COVID-19 infection, the study period ended March 7, 2020. Adjusted analyses were conducted through inverse probability of treatment weighting (IPTW) to control for selection bias. Poisson regression was used to estimate the adjusted pairwise rVE against influenza-related hospitalizations/ER visits, all-cause hospitalizations and any hospitalization/ER visit for CRD. An unrelated negative control outcome, urinary tract infection (UTI) hospitalization was included. Results During the 2019-20 influenza season, following IPTW, 798,987 recipients of aTIV and 1,655,979 recipients of TIV-HD were identified. After IPTW adjustment and Poisson regression, aTIV was statistically comparable to TIV-HD for prevention of influenza-related hospitalizations/ER visits (3.1%; 95% CI: -2.8%-8.6%) and all-cause hospitalizations (-0.7%; 95% CI: -1.6%-0.3%). Similar comparable outcomes were found for reduction of any hospitalization/ER visit for CRD (0.9%; 95% CI: 0.0%-1.7%). No treatment effect was identified for the negative control outcome. Conclusion aTIV and TIV-HD demonstrated comparable reductions in influenza-related hospitalizations/ER visits, all-cause hospitalizations and hospitalizations/ER visits for CRD. Disclosures myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support) Victoria Divino, PhD, Seqirus (Consultant) Stephen I. Pelton, MD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Drishti Shah, PhD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Mitchell DeKoven, PhD, Seqirus (Consultant)


Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 862
Author(s):  
Constantina Boikos ◽  
Mahrukh Imran ◽  
Van Hung Nguyen ◽  
Thierry Ducruet ◽  
Gregg C. Sylvester ◽  
...  

MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) and high-dose trivalent inactivated influenza vaccine (HD-IIV3) elicit an enhanced immune response in older adults compared to standard, quadrivalent inactivated influenza vaccines (IIV4). We sought to determine the relative vaccine effectiveness (rVE) of aIIV3 versus IIV4 and HD-IIV3 in preventing influenza-related medical encounters in this retrospective cohort study involving adults ≥65 years with ≥1 health condition during the 2017–2018 and 2018–2019 influenza seasons. Data were obtained from primary and specialty care electronic medical records linked with pharmacy and medical claims. Adjusted odds ratios (OR) were derived from an inverse probability of treatment-weighted sample adjusted for age, sex, race, ethnicity, geographic region, vaccination week, and health status. rVE was determined using the formula (% rVE = 1 − ORadjusted) × 100. Analysis sets included 1,755,420 individuals for the 2017–2018 season and 2,055,012 for the 2018–2019 season. Compared to IIV4, aIIV3 was 7.1% (95% confidence interval 3.3–10.8) and 20.4% (16.2–24.4) more effective at preventing influenza-related medical encounters in the 2017–2018 and 2018–2019 seasons, respectively. Comparable effectiveness was observed with HD-IIV3 across both seasons. Our results support improved effectiveness of aIIV3 vs IIV4 in a vulnerable population of older adults at high risk of influenza and its complications.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S764-S764 ◽  
Author(s):  
Lee-Jah Chang ◽  
Ya Meng ◽  
Helene Janosczyk ◽  
Victoria Landolfi ◽  
H Keipp Talbot ◽  
...  

Abstract Background Older adults (≥65 years of age) remain at increased risk of influenza because they do not respond to standard dose influenza vaccines as well as younger adults. A high dose, inactivated trivalent influenza vaccine, IIV3-HD, containing four times the antigen content (60 µg hemagglutinin per influenza strain) of standard-dose influenza vaccines has been available in the United States since 2010. Two distinct B influenza lineages (Victoria and Yamagata) have co-circulated for over a decade, making it difficult to predict which will predominate the next season. IIV4-HD has been developed to address the frequent influenza B strain mismatches by incorporating a strain from each B lineage. This pivotal Phase III study evaluated the safety and immunogenicity of IIV4-HD as compared with two IIV3-HD vaccines. Method A randomized, modified double-blind, multicenter study (NCT03282240) was conducted in 2670 healthy subjects in the United States, who were randomly assigned to receive IIV4-HD, a licensed IIV3-HD, or an IIV3-HD with the alternate B influenza strain. Using the hemagglutinin inhibition (HAI) assay at baseline and 28 days after vaccination, post-vaccination geometric mean titers and seroconversion rates were measured. Safety data were collected through 6 months post-vaccination. Result IIV4-HD was noninferior to the licensed IIV3-HD and the investigational IIV3-HD (containing the alternate B strain) for all four influenza strains as assessed by HAI GMTs and seroconversion rates. Moreover, IIV4-HD induced a superior immune response (HAI GMTs and seroconversion rates) compared with the immune response induced by the IIV3-HD that does not contain the corresponding B strain. Reactogenicity profiles were comparable across all study groups. Most unsolicited adverse events were of Grade 1 or Grade 2 intensity. One serious adverse event considered related by the Investigator was reported in the IIV4-HD group. Conclusion Vaccination of adults 65 years of age and older with IIV4-HD was found to be noninferior to two IIV3-HD vaccines with a similar safety profile. The addition of a second B lineage strain does not adversely affect the safety or immunogenicity profile of IIV4-HD compared with IIV3-HD. Disclosures L. J. Chang, Sanofi Pasteur: Employee, Salary. Y. Meng, Sanofi Pasteur: Employee, Salary. H. Janosczyk, Sanofi Pasteur: Employee, Salary. V. Landolfi, Sanofi Pasteur: Employee, Salary. H. K. Talbot, Sanofi Pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.


2020 ◽  
Vol 71 (10) ◽  
pp. e665-e671 ◽  
Author(s):  
Constantina Boikos ◽  
Gregg C Sylvester ◽  
John S Sampalis ◽  
James A Mansi

Abstract Background Influenza antigens may undergo adaptive mutations during egg-based vaccine production. In the 2017–2018 influenza season, quadrivalent, inactivated cell-derived influenza vaccine (ccIIV4) vaccine was produced using A(H3N2) seed virus propagated exclusively in cell culture, thus lacking egg adaptive changes. This United States study estimated relative vaccine effectiveness (rVE) of ccIIV4 vs egg-derived quadrivalent vaccines (egg-derived IIV4) for that season. Methods Vaccination, outcome, and covariate data were ascertained retrospectively from a electronic medical record (EMR) dataset and analyzed. The study cohort included patients ≥ 4 years of age. rVE was estimated against influenza-like illness (ILI) using diagnostic International Classification of Diseases, Ninth or Tenth Revision codes. The adjusted odds ratios used to derive rVE estimates were estimated from multivariable logistic regression models adjusted for age, sex, race/ethnicity, geographic region, and health status. Results Overall, 92 187 individuals had a primary care EMR record of ccIIV4 and 1 261 675 had a record of egg-derived IIV4. In the ccIIV4 group, 1705 narrowly defined ILI events occurred, and 25 645 occurred in the standard egg-derived IIV4 group. Crude rVE was 9.2% (95% confidence interval [CI], 4.6%–13.6%). When adjusted for age, sex, health status, comorbidities, and geographic region, the estimated rVE changed to 36.2% (95% CI, 26.1%–44.9%). Conclusions ccIIV4, derived from A(H3N2) seed virus propagated exclusively in cell culture, was more effective than egg-derived IIV4 in preventing ILI during the 2017–2018 influenza season. This result suggests that cell-derived influenza vaccines may have greater effectiveness than standard egg-derived vaccines.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S10-S10
Author(s):  
Joshua Doyle ◽  
Lauren Beacham ◽  
Elif Alyanak ◽  
Manjusha Gaglani ◽  
Emily T Martin ◽  
...  

Abstract Background Seasonal influenza causes substantial morbidity and mortality, and older adults are disproportionately affected. Newer vaccines have been developed for use in people 65 years and older, including a trivalent inactivated vaccine with a 4-fold higher dose of antigen (IIV-HD). In recent years, the use of IIV-HD has increased sufficiently to evaluate its effectiveness compared with standard-dose inactivated influenza vaccines (IIV-SD). Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in 4 states participating in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Predominant influenza A virus subtypes were H1N1 and H3N2, respectively, during these seasons. All enrolled patients were tested for influenza virus with polymerase chain reaction. Receipt and type of influenza vaccine was determined from electronic records and chart review. Odds of laboratory-confirmed influenza were compared among vaccinated and unvaccinated patients. Relative odds of laboratory-confirmed influenza were determined for patients who received IIV-HD or IIV-SD, and adjusted for potential confounding variables via logistic regression. Results Among 1,744 enrolled patients aged ≥ 65 years, 1,105 (63%) were vaccinated; among those vaccinated, 621 (56%) received IIV-HD and 484 (44%) received IIV-SD. Overall, 315 (18%) tested positive for influenza, including 97 (6%) who received IIV-HD, 86 (5%) who received IIV-SD, and 132 (8%) who were unvaccinated. Controlling for age, race, sex, enrollment site, date of illness, index of comorbidity, and influenza season, the adjusted odds of influenza among patients vaccinated with IIV-HD vs. IIV-SD were 0.72 (P = 0.06, 95% CI: 0.52 to 1.01). Conclusion Comparison of high-dose vs. standard-dose vaccine effectiveness during 2 recent influenza seasons (1 H1N1 and 1 H3N2-predominant) suggested relative benefit (nonsignificant) of high-dose influenza vaccine in protecting against influenza-associated hospitalization among persons aged 65 years and older; additional years of data are needed to confirm this finding. Disclosures H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.


Author(s):  
Joshua D Doyle ◽  
Lauren Beacham ◽  
Emily T Martin ◽  
H Keipp Talbot ◽  
Arnold Monto ◽  
...  

Abstract Background Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged ≥65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. Results Among 1487 enrolled patients aged ≥65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV, and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] −42%, 38%) and that of HD-IIV was 32% (95% CI −3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95% CI −1%, 48%). Conclusions During 2 US influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged ≥65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Marina Amaral de Avila Machado ◽  
Cristiano S. Moura ◽  
Michal Abrahamowicz ◽  
Brian J. Ward ◽  
Louise Pilote ◽  
...  

AbstractInfluenza immunization protects seniors against influenza and its potentially serious complications. It is uncertain whether standard-dose (SD) quadrivalent vaccine offers better protection over other formulations in the elderly. In this study, we compared the effectiveness of SD-trivalent, high-dose (HD) trivalent, SD-quadrivalent, and adjuvanted trivalent vaccines in seniors (≥65 years) in a real-world setting. We selected over 200,000 individuals in each of 6 influenza seasons from 2012 to 2018 using MarketScan® databases. The two outcomes were hospitalization or emergency room (ER) visit due to (1) influenza or (2) pneumonia. Here, SD-quadrivalent was associated with higher risk of influenza-related hospitalization/ER visit (adjusted hazard ratio (aHR) 1.14 and 95% confidence interval (95% CI) 1.05–1.24) and of pneumonia-related hospitalization/ER visit (aHR 1.04 and 95% CI 1.01–1.07) vs. HD-trivalent. SD-trivalent followed similar trends compared to HD-trivalent (aHR 1.16 and 95% CI 1.06–1.27 for hospitalized/ER visit influenza; aHR 1.07 and 95% CI 1.05–1.10 for hospitalized/ER visit pneumonia). We could not demonstrate risk differences between SD vaccine formulations and between adjuvanted trivalent and one of the other three vaccines. Risk estimates slightly varied across seasons. These findings suggest that SD vaccine formulations vs. HD-trivalent were associated with higher risk of hospitalization/ER visit for influenza and pneumonia in seniors.


2018 ◽  
Vol 220 (8) ◽  
pp. 1255-1264 ◽  
Author(s):  
Hector S Izurieta ◽  
Yoganand Chillarige ◽  
Jeffrey Kelman ◽  
Yuqin Wei ◽  
Yun Lu ◽  
...  

Abstract Background The low influenza vaccine effectiveness (VE) observed during the A(H3N2)-dominated 2017–2018 season may be due to vaccine virus adaptation to growth in eggs. We compared the effectiveness of cell-cultured and egg-based vaccines among Medicare beneficiaries. Methods Retrospective cohort study on Medicare beneficiaries aged ≥65 years who received an influenza vaccine (cell-cultured, egg-based quadrivalent; egg-based high-dose, adjuvanted, or standard-dose trivalent) during the 2017–2018 season. We used Poisson regression to evaluate relative VE (RVE) in preventing influenza-related hospital encounters. Results Of >13 million beneficiaries, RVE for cell-cultured vaccines relative to egg-based quadrivalent vaccines was 10% (95% confidence interval [CI], 7%–13%). In a midseason interim analysis, this estimate was 16.5% (95% CI, 10.3%–22.2%). In a 5-way comparison, cell-cultured (RVE, 11%; 95% CI, 8%–14%) and egg-based high-dose (RVE, 9%; 95% CI, 7%–11%) vaccines were more effective than egg-based quadrivalent vaccines. Conclusions The modest VE difference between cell-cultured and egg-based vaccines only partially explains the low overall VE reported by the Centers for Disease Control and Prevention, suggesting that egg adaptation was not the main contributor to the low VE found among individuals aged ≥65 years. The midseason interim analysis we performed demonstrates that our methods can be used to evaluate VE actively during the influenza season.


2020 ◽  
Vol 222 (2) ◽  
pp. 278-287 ◽  
Author(s):  
Hector S Izurieta ◽  
Yoganand Chillarige ◽  
Jeffrey Kelman ◽  
Yuqin Wei ◽  
Yun Lu ◽  
...  

Abstract Background Studies among individuals ages ≥65 years have found a moderately higher relative vaccine effectiveness (RVE) for the high-dose (HD) influenza vaccine compared with standard-dose (SD) products for most seasons. Studies during the A(H3N2)-dominated 2017–2018 season showed slightly higher RVE for the cell-cultured vaccine compared with SD egg-based vaccines. We investigated the RVE of influenza vaccines among Medicare beneficiaries ages ≥65 years during the 2018–2019 season. Methods This is a retrospective cohort study using inverse probability of treatment weighting and Poisson regression to evaluate RVE in preventing influenza hospital encounters. Results Among 12 777 214 beneficiaries, the egg-based adjuvanted (RVE, 7.7%; 95% confidence interval [CI], 3.9%–11.4%) and HD (RVE, 4.9%; 95% CI, 1.7%–8.1%) vaccines were marginally more effective than the egg-based quadrivalent vaccines. The cell-cultured quadrivalent vaccine was not significantly more effective than the egg-based quadrivalent vaccine (RVE, 2.5%; 95% CI, −2.4% to 7.3%). Conclusions We did not find major effectiveness differences between licensed vaccines used among the elderly during the 2018–2019 season. Consistent with prior research, we found that the egg-based adjuvanted and HD vaccines were slightly more effective than the egg-based quadrivalent vaccines.


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