Carlos A DiazGranados1, Andrew J Dunning2, Corwin A Robertson2, H Keipp Talbot3, Victoria Landolfi2, David P Greenberg4. 1. Sanofi Pasteur, 1 Discovery Drive, Swiftwater, PA 18370, United States. Electronic address: carlos.diazgranados@sanofipasteur.com. 2. Sanofi Pasteur, 1 Discovery Drive, Swiftwater, PA 18370, United States. 3. Vanderbilt University Medical Center, A2200 MCN 1161 21st Ave S, Nashville, TN 37232, United States. 4. Sanofi Pasteur, 1 Discovery Drive, Swiftwater, PA 18370, United States; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States.
Abstract
BACKGROUND: A randomized trial demonstrated that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose vaccine (IIV-SD) against laboratory-confirmed influenza illness in adults ≥65 years. To evaluate the consistency of IIV-HD benefits, supplemental analyses explored efficacy and immunogenicity by baseline characteristics of special interest. METHODS: Double-blind, randomized, active-controlled, multicenter trial. Adults ≥65 years were randomized 1:1 to receive IIV-HD or IIV-SD and followed for 6-8 months postvaccination for the occurrence of influenza. One third of participants were randomly selected to provide sera for measurement of hemagglutination inhibition antibody (HAI) titers. Efficacy (IIV-HD vs. IIV-SD) against laboratory-confirmed, protocol-defined influenza-like illness (PD-ILI) and HAI geometricmean titer (GMT) ratios (IIV-HD/IIV-SD) were evaluated by age, and number of high-risk comorbid and frailty conditions. RESULTS:Efficacy (95% confidence intervals) of IIV-HD relative to IIV-SD against laboratory-confirmed PD-ILI was 19.7% (0.4%; 35.4%) for participants 65-74 years, 32.4% (8.1%; 50.6%) for those ≥75 years, 22.1% (3.9%; 37.0%) for participants with ≥1 high-risk comorbidity, 23.6% (-3.2%; 43.6%) for those with ≥2 high-risk comorbidities, 27.5% (0.4%; 47.4%) for persons with 1 frailty condition, 23.9% (-9.0%; 47.2%) for those with 2 frailty conditions, and 16.0% (-16.3%; 39.4%) for those with ≥3 frailty conditions. There was no evidence of vaccine efficacy heterogeneity within age, comorbidity, and frailty strata (P-values 0.351, 0.875, and 0.838, respectively). HAI GMT ratios were significantly higher among IIV-HD recipients for all strains and across all subgroups. CONCLUSIONS: Estimates of relative efficacy consistently favored IIV-HD over IIV-SD. There was no significant evidence that baseline age, comorbidity, or frailty modified the efficacy of IIV-HD relative to IIV-SD. IIV-HD significantly improved HAI responses for all strains and in all subgroups. IIV-HD is likely to provide benefits beyond IIV-SD for adults ≥65 years, irrespective of age and presence of comorbid or frailty conditions.
RCT Entities:
BACKGROUND: A randomized trial demonstrated that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose vaccine (IIV-SD) against laboratory-confirmed influenza illness in adults ≥65 years. To evaluate the consistency of IIV-HD benefits, supplemental analyses explored efficacy and immunogenicity by baseline characteristics of special interest. METHODS: Double-blind, randomized, active-controlled, multicenter trial. Adults ≥65 years were randomized 1:1 to receive IIV-HD or IIV-SD and followed for 6-8 months postvaccination for the occurrence of influenza. One third of participants were randomly selected to provide sera for measurement of hemagglutination inhibition antibody (HAI) titers. Efficacy (IIV-HD vs. IIV-SD) against laboratory-confirmed, protocol-defined influenza-like illness (PD-ILI) and HAI geometric mean titer (GMT) ratios (IIV-HD/IIV-SD) were evaluated by age, and number of high-risk comorbid and frailty conditions. RESULTS: Efficacy (95% confidence intervals) of IIV-HD relative to IIV-SD against laboratory-confirmed PD-ILI was 19.7% (0.4%; 35.4%) for participants 65-74 years, 32.4% (8.1%; 50.6%) for those ≥75 years, 22.1% (3.9%; 37.0%) for participants with ≥1 high-risk comorbidity, 23.6% (-3.2%; 43.6%) for those with ≥2 high-risk comorbidities, 27.5% (0.4%; 47.4%) for persons with 1 frailty condition, 23.9% (-9.0%; 47.2%) for those with 2 frailty conditions, and 16.0% (-16.3%; 39.4%) for those with ≥3 frailty conditions. There was no evidence of vaccine efficacy heterogeneity within age, comorbidity, and frailty strata (P-values 0.351, 0.875, and 0.838, respectively). HAI GMT ratios were significantly higher among IIV-HD recipients for all strains and across all subgroups. CONCLUSIONS: Estimates of relative efficacy consistently favored IIV-HD over IIV-SD. There was no significant evidence that baseline age, comorbidity, or frailty modified the efficacy of IIV-HD relative to IIV-SD. IIV-HD significantly improved HAI responses for all strains and in all subgroups. IIV-HD is likely to provide benefits beyond IIV-SD for adults ≥65 years, irrespective of age and presence of comorbid or frailty conditions.
Authors: Jin Hyang Kim; H Keipp Talbot; Margarita Mishina; Yuwei Zhu; Jufu Chen; Weiping Cao; Adrian J Reber; Marie R Griffin; David K Shay; Sarah M Spencer; Suryaprakash Sambhara Journal: Vaccine Date: 2016-07-26 Impact factor: 3.641
Authors: Anne M Butler; J Bradley Layton; Vikas R Dharnidharka; John M Sahrmann; Marissa J Seamans; David J Weber; Leah J McGrath Journal: Am J Kidney Dis Date: 2019-08-01 Impact factor: 8.860
Authors: Hana Hakim; Kim J Allison; Lee-Ann Van de Velde; Li Tang; Yilun Sun; Patricia M Flynn; Jonathan A McCullers Journal: Vaccine Date: 2016-04-26 Impact factor: 3.641
Authors: Jessica R Cataldi; Laura P Hurley; Megan C Lindley; Sean T O'Leary; Carol Gorman; Michaela Brtnikova; Brenda L Beaty; Lori A Crane; David K Shay; Allison Kempe Journal: J Gen Intern Med Date: 2021-01-22 Impact factor: 6.473
Authors: Joshua D Doyle; Lauren Beacham; Emily T Martin; H Keipp Talbot; Arnold Monto; Manjusha Gaglani; Donald B Middleton; Fernanda P Silveira; Richard K Zimmerman; Elif Alyanak; Emily R Smith; Brendan L Flannery; Melissa Rolfes; Jill M Ferdinands Journal: Clin Infect Dis Date: 2021-03-15 Impact factor: 9.079