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. Objectives: 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.