Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab
Abstract
Objective: For patients with rheumatoid arthritis (RA), yearly influenza vaccination is recommended. However, its efficacy in patients treated with rituximab is unknown. The objectives of this study were to investigate the efficacy of influenza vaccination in RA patients treated with rituximab and to investigate the duration of the possible suppression of the humoral immune response following rituximab treatment. We also undertook to assess the safety of influenza vaccination and the effects of previous influenza vaccination. Methods: Trivalent influenza subunit vaccine was administered to 23 RA patients who had received rituximab (4–8 weeks after rituximab for 11 patients [the early rituximab subgroup] and 6–10 months after rituximab for 12 patients [the late rituximab subgroup]), 20 RA patients receiving methotrexate (MTX), and 29 healthy controls. Levels of antibodies against the 3 vaccine strains were measured before and 28 days after vaccination using hemagglutination inhibition assay. The Disease Activity Score in 28 joints (DAS28) was used to assess RA activity. Results: Following vaccination, geometric mean titers (GMTs) of antiinfluenza antibodies significantly increased for all influenza strains in the MTX‐treated group and in healthy controls, but for no strains in the rituximab‐treated group. However, in the late rituximab subgroup, a rise in GMT for the A/H3N2 and A/H1N1 strains was demonstrated, in the absence of a repopulation of CD19+ cells at the time of vaccination. Seroconversion and seroprotection occurred less often in the rituximab‐treated group than in the MTX‐treated group for the A/H3N2 and A/H1N1 strains, while seroprotection occurred less often in the rituximab‐treated group than in the healthy controls for the A/H1N1 strain. Compared with unvaccinated patients in the rituximab‐treated group, previously vaccinated patients in the rituximab‐treated group had higher pre‐ and postvaccination GMTs for the A/H1N1 strain. The DAS28 did not change after vaccination. Conclusion: Rituximab reduces humoral responses following influenza vaccination in RA patients, with a modestly restored response 6–10 months after rituximab administration. Previous influenza vaccination in rituximab‐treated patients increases pre‐ and postvaccination titers. RA activity was not influenced.
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Prior data show anti-CD20 therapy negatively impacts humoral response to various vaccines, though seroprotection can still occur in rituximab- and ocrelizumab-treated patients.
“Our findings are in line with the previously published data regarding the negative impact of anti-CD20 therapy on the humoral response to various vaccines, although seroprotection could be still achieved after vaccination in rituximab-treated 20 26 34-36 and ocrelizumab-treated 37 patients.”
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- Authors
- van Assen, S., Holvast, A., Benne, C. A., Posthumus, M. D., van Leeuwen, M. A., Voskuyl, A. E., Blom, M., Risselada, A. P., de Haan, A., Westra, J., Kallenberg, C. G. M., & Bijl, M.
- Affiliations
- University Medical Center Groningen (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Radboud University Nijmegen (NL)
- University Medical Center Utrecht (NL)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2009-12-28
- Volume
- 62
- Issue
- 1
- Pages
- 75-81
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2059903231
- Cited by
- 371
- References
- 18
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 21 · 2023: 20 · 2022: 35 · 2021: 57 · 2020: 30 · 2019: 11 · 2018: 17 · 2017: 14 · 2016: 14 · 2015: 20 · 2014: 23 · 2013: 24 · 2012: 15
- FWCI
- 15.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Keywords
- rheumatoid arthritis, rituximab, influenza vaccination, humoral immune response, influenza antibodies, seroprotection, seroconversion, methotrexate, CD19+ B cells, vaccine efficacy, disease activity, trivalent influenza vaccine, B-cell depletion, hemagglutination inhibition test, DAS28
- MeSH terms
- Rituximab, Antibodies, Monoclonal, Antibodies, Viral, Arthritis, Rheumatoid, Drug Therapy, Combination, Female, Hemagglutination Inhibition Tests, Humans, Immunization Schedule, Immunologic Memory, Influenza Vaccines, Male, Methotrexate, Middle Aged, Vaccines, Inactivated, B-Lymphocyte Subsets, Antirheumatic Agents, Antigens, CD20, Immunity, Humoral, Antibodies, Monoclonal, Murine-Derived
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