Prevention of serious events in adults 65 years of age or older: A comparison between high-dose and standard-dose inactivated influenza vaccines

• Published in: Vaccine Vol. 33; no. 38; pp. 4988 - 4993
• Main Authors: DiazGranados, Carlos A., Robertson, Corwin A., Talbot, H. Keipp, Landolfi, Victoria, Dunning, Andrew J., Greenberg, David P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 11.09.2015; Elsevier Limited
• Subjects: Aged; Aged, 80 and over; Allergy and Immunology; Chronic obstructive pulmonary disease; Clinical trial, phase III; complications (disease); confidence interval; death; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - prevention & control; elderly; Female; Hospitalization; Humans; Immunization; Influenza; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza vaccines, human; Influenza, Human - pathology; Influenza, Human - prevention & control; Male; Older people; physicians; pneumonia; Prevention; risk reduction; Survival Analysis; Vaccines; Vaccines, inactivated; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - adverse effects; RR; rVE; CI; Clinical trial, phase III; ITT; Vaccines, inactivated; IIV-HD; CAP; Influenza vaccines, human; IIV-SD; SAE; Aged, 80 and over; FAS; Aged; COPD; relative vaccine effectiveness; intent-to-treat; standard-dose inactivated influenza vaccine; serious adverse event; high-dose inactivated influenza vaccine; rate ratios; community-acquired pneumonia; Full Analysis Set; confidence interval; chronic obstructive pulmonary disease
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2015.07.006

•Randomized trial of high-dose vs. standard-dose influenza vaccines in older adults.•High-dose vaccine decreased the risk of serious cardio-respiratory events.•The relative effectiveness against serious pneumonia was 39.8%. A recent study showed that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose inactivated influenza vaccine (IIV-SD) in preventing laboratory-confirmed symptomatic influenza in adults ≥65 years. Here we evaluate the effectiveness of IIV-HD compared to IIV-SD in preventing serious illnesses considered potential sequelae or complications of influenza infection. The original study was a double-blind, randomized, active-controlled, multicenter trial. Participants were adults ≥65 years randomized to receive IIV-HD or IIV-SD, and followed for 6–8 months post-vaccination for the occurrence of influenza and serious adverse events (SAEs). SAEs were events: leading to death or hospitalization (or its prolongation); considered life-threatening or medically important; or resulting in disability. For the present analysis, reported SAEs were classified as possibly related to influenza by three blinded physicians and rates per 1000 participant-seasons were calculated. Relative vaccine effectiveness (rVE) was estimated as (1−Rate Ratio)×100. 31,989 participants were enrolled, with 15,991 and 15,998 randomized to receive IIV-HD and IIV-SD, respectively. IIV-HD was significantly more effective than IIV-SD in preventing SAEs possibly related to influenza overall (rVE, 17.7%; 95% confidence interval [CI], 6.6–27.4%) and serious pneumonia (rVE, 39.8%; 95% CI, 19.3–55.1%). Borderline significance was observed for the efficacy of IIV-HD relative to IIV-SD for the prevention of all-cause hospitalizations (rVE, 6.9%; 95% CI, 0.5–12.8%). Compared to IIV-SD, IIV-HD reduced the risk of SAEs possibly related to influenza. The observed relative effectiveness against serious pneumonia is particularly noteworthy considering the burden of influenza and pneumonia in older adults.