Influenza symptoms and their impact on elderly adults: randomised trial of AS03-adjuvanted or non-adjuvanted inactivated trivalent seasonal influenza vaccines.
BACKGROUND
Patient-reported outcomes (PROs) are particularly relevant in influenza vaccine trials in the elderly where reduction in symptom severity could prevent illness-related functional impairment.


OBJECTIVE
To evaluate PROs in people aged ≥ 65 years receiving two different vaccines.


METHODS
This was a phase III, randomised, observer-blind study (NCT00753272) of the AS03-adjuvanted inactivated trivalent split-virion influenza vaccine (AS03-TIV) versus non-adjuvanted vaccine (TIV). Using the FluiiQ questionnaire, symptom (systemic, respiratory, total) and life impact (activities, emotions, relationships) scores were computed as exploratory endpoints, with minimal important difference (MID) in influenza severity between vaccines considered post-hoc as >7%. Vaccine efficacy of AS03-TIV relative to TIV in severe influenza (hospitalisation, complication, most severe one-third of episodes based on the area under the curve for systemic symptom score) was calculated post-hoc. The main analyses (descriptive) were conducted in the according-to-protocol cohort (n = 280 AS03-TIV, n = 315 TIV) for influenza confirmed by culture or reverse transcriptase polymerase chain reaction.


RESULTS
Mean systemic symptom, total symptom and impact on activities scores were lower with AS03-TIV versus TIV. Mean respiratory symptom, impact on emotions and impact on relationships scores were similar. Influenza tended to be less severe with AS03-TIV, but the MID was reached only for impact on activities (mean 9.0%). Relative vaccine efficacy in severe influenza was 29.38% (95% CI: 7.60-46.02).


CONCLUSIONS
AS03-TIV had advantages over TIV in impact on systemic symptoms and activities as measured by the FluiiQ in elderly people. Higher efficacy of AS03-TIV relative to TIV was shown for prevention of severe illness.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Gerrit A
GA
van Essen
Jiri
J
Beran
Jeanne-Marie
JM
Devaster
Christelle
C
Durand
Xavier
X
Duval
Meral
M
Esen
Ann R
AR
Falsey
Gregory
G
Feldman
Pierre
P
Gervais
Bruce L
BL
Innis
Martina
M
Kovac
Odile
O
Launay
Geert
G
Leroux-Roels
Janet E
JE
McElhaney
Shelly
S
McNeil
Mohammed
M
Oujaa
Jan Hendrik
JH
Richardus
Guillermo
G
Ruiz-Palacios
Richard H
RH
Osborne
Lidia
L
Oostvogels
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D013185:Squalene
AS03-adjuvanted vaccine; FluiiQ; elderly; influenza; patient-reported outcomes