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 |
| |
| Affiliation: | 1. Department of Internal Medicine and Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, United States;2. Microbiology and Immunology, The University of Iowa, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, United States;3. Research and Medical Services, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, United States;4. The Emmes Corporation, Rockville, MD, United States;5. Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States;1. UMR Vitrome, Institut de Recherche Pour le Développement, Dakar, Senegal;2. Center for Vaccine Innovation and Access, PATH, Seattle, USA;3. Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA;4. Kanesa, LLC, Cambridge, USA;5. Senegal Ministry of Health and Social Welfare, Dakar, Senegal;6. Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, USA;7. Division of Global Health Protection, CDC Kenya, Center for Global Health, Centers for Disease Control and Prevention, Nairobi, Kenya;8. Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, USA;1. Université Paris Descartes, Sorbonne Paris Cité AP-HP, Unité de Biostatistique et Epidémiologie, Groupe Hospitalier Cochin Broca Hôtel-Dieu, Paris, France;2. INSERM, UPMC Université Paris 06, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France;3. Université Paris Descartes, Sorbonne Paris Cité AP-HP, Service de Médecine Interne, Centre de Référence National pour les Maladies Auto-Immunes Rares (Vascularites et Sclérodermie Systémique), Paris, France;4. Université Paris Descartes, Sorbonne Paris Cité AP-HP, Département d’Immunologie Biologique, Groupe Hospitalier Cochin Broca Hôtel-Dieu, Paris, France;5. Inserm, CIC 1417, Paris, France;6. Université Pierre et Marie Curie, Sorbonne Paris Cité AP-HP, Service de Médecine Interne 2, Centre de Référence National pour le Lupus et le Syndrome des Antiphospholipides, institut E3M, Paris, France;7. Université Versailles Saint-Quentin-en-Yvelines, APHP, Service de Médecine Interne, Hôpital Ambroise Paré, Boulogne-Billancourt, France;8. Université Paris Descartes, Sorbonne Paris Cité AP-HP, Groupe Hospitalier Cochin Broca Hôtel-Dieu, Fédération d''Infectiologie, Paris, France;9. Inserm, F-CRIN I-REIVAC, France;1. Department of Pediatrics, Houston, TX, United States;2. Department of Molecular Virology and Microbiology, Houston, TX, United States;3. Department of Medicine, Baylor College of Medicine, Houston, TX, United States;4. Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States;5. Department of Obstetrics & Gynecology, Duke University, Durham, NC, United States;6. Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University, Nashville, TN, United States;7. Saint Louis University School of Medicine, St. Louis, MO, United States;8. The EMMES Company, LLC, Rockville, MD, United States;1. Rhumatologie, centre hospitalier Princesse Grâce, boulevard Pasteur, 98000 Monaco, Monaco;2. Service de rhumatologie, hôpital Archet 1, université de Nice, 06200 Nice, France;3. Département d’information médicale, CHPG, 98000 Monaco, Monaco;4. Service de rhumatologie, centre hospitalier de Cannes, 06400 Cannes, France;5. Service de rhumatologie, centre hospitalier Fréjus-Saint-Raphaël, 83800 Saint-Raphaël, France;1. Infectious Diseases Division, Paulista School of Medicine, Federal University of São Paulo, Brazil;2. Laboratório Centro de Genomas, São Paulo, Brazil;3. Department of Infectious Diseases, Nossa Senhora das Graças, Curitiba, Paraná, Brazil;1. Department of Nephrology, University of Heidelberg, Heidelberg, Germany;2. Department of Molecular Medicine Partnership Unit Heidelberg, European Molecular Biology Laboratory, Heidelberg, Germany;3. Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany;4. Department of Virology, University of Heidelberg, Heidelberg, Germany;5. German Center for Infection Research, Heidelberg partner site, Heidelberg, Germany;6. Institute of Immunology, University of Heidelberg, Heidelberg, Germany;7. Division Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany |
| |
| Abstract: | IntroductionSubjects 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.MethodsA 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.ResultsA 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).ConclusionsTNF-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: | Rheumatoid arthritis TNFalpha Inhibitor Influenza Vaccine |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
