Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults

Key Points Question What are the comparative safety, reactogenicity, and short-term effects of vaccination on health-related quality of life after trivalent adjuvanted inactivated influenza vaccine (aIIV3) or trivalent high-dose inactivated influenza vaccine (HD-IIV3) in adults aged 65 years and older? Findings In this randomized clinical trial of 757 older adults (378 receiving aIIV3 and 379 receiving HD-IIV3), the proportion of participants with moderate-to-severe injection-site pain (primary outcome) was not higher after aIIV3 than HD-IIV3. No vaccine-related serious adverse events occurred, and postvaccination health-related quality of life was similar between aIIV3 and IIV3-HD groups. Meaning These findings suggest that from a safety standpoint, aIIV3 or HD-IIV3 is an acceptable option to prevent influenza in older adults.
This randomized clinical trial assesses whether injection-site pain and reactogenicity are noninferior in trivalent adjuvanted inactivated influenza vaccine (aIIV3) compared with trivalent high-dose inactivated influenza vaccine (HD-IIV3) among adults aged 65 years and older.
Importance Trivalent adjuvanted inactivated influenza vaccine (aIIV3) and trivalent high-dose inactivated influenza vaccine (HD-IIV3) are US-licensed for adults aged 65 years and older. Data are needed on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of these vaccines. Objective To compare safety, reactogenicity, and changes in HRQOL scores after aIIV3 vs HD-IIV3. Design, Setting, and Participants This randomized blinded clinical trial was a multicenter US study conducted during the 2017 to 2018 and 2018 to 2019 influenza seasons. Among 778 community-dwelling adults aged at least 65 years and assessed for eligibility, 13 were ineligible and 8 withdrew before randomization. Statistical analysis was performed from August 2019 to August 2020. Interventions Intramuscular administration of aIIV3 or HD-IIV3 after age-stratification (65-79 years; ≥80 years) and randomization. Main Outcomes and Measures Proportions of participants with moderate-to-severe injection-site pain and 14 other solicited reactions during days 1 to 8, using a noninferiority test (5% noninferiority margin), and serious adverse events (SAE) and adverse events of clinical interest (AECI), including new-onset immune-mediated conditions, during days 1 to 43. Changes in HRQOL scores before and after vaccination (days 1, 3) were also compared between study groups. Results A total of 757 adults were randomized, 378 to receive aIIV3 and 379 to receive HD-IIV3. Of these participants, there were 420 women (55%) and 589 White individuals (78%) with a median (range) age of 72 (65-97) years. The proportion reporting moderate-to-severe injection-site pain, limiting or preventing activity, after aIIV3 (12 participants [3.2%]) (primary outcome) was noninferior compared with HD-IIV3 (22 participants [5.8%]) (difference −2.7%; 95% CI, −5.8 to 0.4). Ten reactions met noninferiority criteria for aIIV3; 4 (moderate-to-severe injection-site tenderness, arthralgia, fatigue, malaise) did not. It was inconclusive whether these 4 reactions occurred in higher proportions of participants after aIIV3. No participant sought medical care for a vaccine reaction. No AECI was observed. Nine participants had at least SAE after aIIV3 (2.4%; 95% CI,1.1% to 4.5%); 3 had at least 1 SAE after HD-IIV3 (0.8%; 95% CI, 0.2% to 2.2%). No SAE was associated with vaccination. Changes in prevaccination and postvaccination HRQOL scores were not clinically meaningful and not different between the groups. Conclusions and Relevance Overall safety and HRQOL findings were similar after aIIV3 and HD-IIV3, and consistent with prelicensure data. From a safety standpoint, this study’s results support using either vaccine to prevent influenza in older adults. Trial Registration ClinicalTrials.gov Identifier: NCT03183908