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Randomized Controlled Trial
. 2020 May 13;38(23):3934-3941.
doi: 10.1016/j.vaccine.2020.04.002. Epub 2020 Apr 12.

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

Jack T Stapleton  1 , Nancy Wagner  2 , Rebecca Tuetken  2 , Abbie R Bellamy  3 , Heather Hill  3 , Sonnie Kim  4 , Patricia L Winokur  2
Affiliations
Randomized Controlled Trial

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

Jack T Stapleton et al. Vaccine. .

Abstract

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 × 3 strains]) or SD (Sanofi Pasteur Fluzone® [15 mcg × 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.

Keywords: Influenza Vaccine; Rheumatoid arthritis; TNFalpha Inhibitor.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Disposition of Study Study Subjects.
The number of subjects screened and enrolled into the study and their final disposition is shown.
Figure 2.
Figure 2.. Immune Responsed to standard dose (SD) or high dose (HD) trivalent influenza vaccine (TIV).
HAI titers to influenza strains present in TIV administered is shown for participants with rheumatoid arthritis (RA) receiving TNF-alpha inhibitors and control subjects over time.
Figure 3.
Figure 3.. Safety of TIV in study groups.
Grade 1 or grade 2 adverse events (AEs) in participants with rheumatoid arthritis (RA) receiving TNF-alpha inhibitors and control subjects. There were no Grade 3 AEs.,
See this image and copyright information in PMC

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