PMID- 32295718 OWN - NLM STAT- MEDLINE DCOM- 20210315 LR - 20210513 IS - 1873-2518 (Electronic) IS - 0264-410X (Print) IS - 0264-410X (Linking) VI - 38 IP - 23 DP - 2020 May 13 TI - High dose trivalent influenza vaccine compared to standard dose vaccine in patients with rheumatoid arthritis receiving TNF-alpha inhibitor therapy and healthy controls: Results of the DMID 10-0076 randomized clinical trial. PG - 3934-3941 LID - S0264-410X(20)30459-X [pii] LID - 10.1016/j.vaccine.2020.04.002 [doi] AB - INTRODUCTION: Subjects with rheumatoid arthritis (RA) receiving tumor necrosis factor-inhibiting (TNFi) therapies are at risk for severe influenza, and may respond less well to influenza vaccine. We examined the safety and immunogenicity of high dose influenza vaccine (HD) compared to standard dose vaccine (SD) in participants with RA receiving stable TNFi. METHODS: A randomized, double-blinded, Phase II study was conducted in adults with RA receiving TNFi, and healthy, gender and age-matched control subjects. Participants were immunized with HD (Sanofi Pasteur Fluzone High Dose [60 mcg x 3 strains]) or SD (Sanofi Pasteur Fluzone(R) [15 mcg x 3 strains]) intramuscularly (IM). A self-administered memory aid recorded temperature and systemic and local adverse events (AEs) for 8 days, and safety was evaluated and serum obtained to measure HAI activity on days 7, 21 and 180 days following vaccination. RESULTS: A greater proportion of RA subjects who received HD seroconverted at day 21 compared to SD, although this was not statistically significant. GMT antibody responses in RA subjects who received HD compared to SD were greater for all strains on day 21, and this was significant for H1N1. Seroconversion rates and GMT values were not different between RA subjects and control subjects. There were no safety concerns for HD or SD in RA subjects, and RA-related symptoms did not differ between SD and HD recipients by a RA-symptom questionnaire (RAPID 3). CONCLUSIONS: TNF-inhibitor therapy in people with RA did not appear to influence the immunogenicity of either SD or HD. Influenza seroconversion and GMT values were higher among RA subjects receiving HD compared to SD; however, differences were small and a larger study is needed to validate these findings. Given the apparent risk of increased influenza-related morbidity and mortality among immune compromised subjects, the higher GMT values generated by HD may be beneficial. CI - Published by Elsevier Ltd. FAU - Stapleton, Jack T AU - Stapleton JT AD - Department of Internal Medicine and Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, United States; Microbiology and Immunology, The University of Iowa, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, United States; Research and Medical Services, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, United States. Electronic address: jack-stapleton@uiowa.edu. FAU - Wagner, Nancy AU - Wagner N AD - Department of Internal Medicine and Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, United States. FAU - Tuetken, Rebecca AU - Tuetken R AD - Department of Internal Medicine and Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, United States. FAU - Bellamy, Abbie R AU - Bellamy AR AD - The Emmes Corporation, Rockville, MD, United States. FAU - Hill, Heather AU - Hill H AD - The Emmes Corporation, Rockville, MD, United States. FAU - Kim, Sonnie AU - Kim S AD - Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States. FAU - Winokur, Patricia L AU - Winokur PL AD - Department of Internal Medicine and Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, United States. LA - eng GR - HHSN272200800008C/AI/NIAID NIH HHS/United States GR - HHSN272201500002C/AI/NIAID NIH HHS/United States GR - UL1 RR024979/RR/NCRR NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20200412 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Viral) RN - 0 (Indans) RN - 0 (Influenza Vaccines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 7561-62-8 (2-(2,4-dimethylphenyl)indan-1,3-dione) SB - IM MH - Adult MH - Antibodies, Viral MH - *Arthritis, Rheumatoid/complications/drug therapy MH - Female MH - Hemagglutination Inhibition Tests MH - Humans MH - Indans MH - *Influenza A Virus, H1N1 Subtype/immunology MH - *Influenza Vaccines/adverse effects MH - *Influenza, Human/prevention & control MH - Male MH - Reference Standards MH - Tumor Necrosis Factor-alpha PMC - PMC7337238 MID - NIHMS1584169 OTO - NOTNLM OT - Influenza Vaccine OT - Rheumatoid arthritis OT - TNFalpha Inhibitor COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/04/17 06:00 MHDA- 2021/03/16 06:00 PMCR- 2021/05/13 CRDT- 2020/04/17 06:00 PHST- 2019/10/21 00:00 [received] PHST- 2020/03/12 00:00 [revised] PHST- 2020/04/01 00:00 [accepted] PHST- 2020/04/17 06:00 [pubmed] PHST- 2021/03/16 06:00 [medline] PHST- 2020/04/17 06:00 [entrez] PHST- 2021/05/13 00:00 [pmc-release] AID - S0264-410X(20)30459-X [pii] AID - 10.1016/j.vaccine.2020.04.002 [doi] PST - ppublish SO - Vaccine. 2020 May 13;38(23):3934-3941. doi: 10.1016/j.vaccine.2020.04.002. Epub 2020 Apr 12.