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Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial.
JAMA Netw Open. 2021 01 04; 4(1):e2031266.JN

Abstract

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.

Authors+Show Affiliations

Center for the Study of Aging, Division of Geriatrics, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. Geriatric Research Education and Clinical Center, Durham VA Health Care System, Durham, North Carolina.Section of Geriatrics, Division of Primary Care and Population Health, Stanford University, Stanford, California. Geriatric Research and Education Clinical Center, Palo Alto Veterans Affairs Health Care System, Palo Alto, California.Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina.Geriatrics Section, Boston Medical Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina. Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.Section of Pediatric Infectious Diseases, Boston Medical Center, Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts.Cincinnati Children's Hospital and Medical Center, Department of Pediatrics Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina.Cincinnati Children's Hospital and Medical Center, Department of Pediatrics Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio.Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia.Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

33443580

Citation

Schmader, Kenneth E., et al. "Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted Vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: a Randomized Clinical Trial." JAMA Network Open, vol. 4, no. 1, 2021, pp. e2031266.
Schmader KE, Liu CK, Harrington T, et al. Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2021;4(1):e2031266.
Schmader, K. E., Liu, C. K., Harrington, T., Rountree, W., Auerbach, H., Walter, E. B., Barnett, E. D., Schlaudecker, E. P., Todd, C. A., Poniewierski, M., Staat, M. A., Wodi, P., & Broder, K. R. (2021). Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial. JAMA Network Open, 4(1), e2031266. https://doi.org/10.1001/jamanetworkopen.2020.31266
Schmader KE, et al. Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted Vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: a Randomized Clinical Trial. JAMA Netw Open. 2021 01 4;4(1):e2031266. PubMed PMID: 33443580.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial. AU - Schmader,Kenneth E, AU - Liu,Christine K, AU - Harrington,Theresa, AU - Rountree,Wes, AU - Auerbach,Heidi, AU - Walter,Emmanuel B, AU - Barnett,Elizabeth D, AU - Schlaudecker,Elizabeth P, AU - Todd,Chris A, AU - Poniewierski,Marek, AU - Staat,Mary A, AU - Wodi,Patricia, AU - Broder,Karen R, Y1 - 2021/01/04/ PY - 2021/1/14/entrez PY - 2021/1/15/pubmed PY - 2021/3/13/medline SP - e2031266 EP - e2031266 JF - JAMA network open JO - JAMA Netw Open VL - 4 IS - 1 N2 - 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. SN - 2574-3805 UR - https://www.unboundmedicine.com/medline/citation/33443580/Safety_Reactogenicity_and_Health_Related_Quality_of_Life_After_Trivalent_Adjuvanted_vs_Trivalent_High_Dose_Inactivated_Influenza_Vaccines_in_Older_Adults:_A_Randomized_Clinical_Trial_ L2 - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2020.31266 DB - PRIME DP - Unbound Medicine ER -