Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial
Abstract
Objective: To examine immunization responses in patients with rheumatoid arthritis (RA) treated with rituximab and to investigate the effects of rituximab‐induced CD20+ B cell depletion on immune responses to tetanus toxoid (T cell–dependent antigen), pneumococcal polysaccharide (T cell–independent antigen), and keyhole limpet hemocyanin (KLH) (neoantigen) and on delayed‐type hypersensitivity (DTH). Methods: In a controlled trial, we enrolled 103 patients with active RA receiving a stable dose of methotrexate (MTX). Tetanus toxoid, pneumococcal polysaccharide, and KLH vaccines as well as a Candida albicans skin test were administered to 1 group of patients receiving rituximab plus MTX (called rituximab‐treated patients) for 36 weeks and to 1 group of patients receiving MTX alone for 12 weeks. The primary end point was the proportion of patients with a ≥4‐fold rise in antitetanus IgG levels. Antitetanus, antipneumococcal, and anti‐KLH serum IgG levels were measured prior to and 4 weeks following vaccine administration. The DTH response to C albicans was measured 2–3 days following placement. Results: Responses to tetanus toxoid vaccine (≥4‐fold rise) were similar in both groups (39.1% of rituximab‐treated patients and 42.3% of patients treated with MTX alone). The ability to maintain a positive DTH response to the C albicans skin test was comparable in both groups (77.4% of rituximab‐treated patients and 70% of patients treated with MTX alone), showing no effect of rituximab treatment. Rituximab‐treated patients had decreased responses to pneumococcal polysaccharide vaccine (57% of patients had a 2‐fold rise in titer in response to ≥1 serotype, compared with 82% of patients treated with MTX alone) and to KLH vaccine (47% of patients had detectable anti‐KLH IgG, compared with 93% of patients treated with MTX alone). Conclusion: Recall responses to the T cell–dependent protein antigen tetanus toxoid as well as DTH responses were preserved in rituximab‐treated RA patients 24 weeks after treatment. Responses to neoantigen (KLH) and T cell–independent responses to pneumococcal vaccine were decreased, but many patients were able to mount responses. These data suggest that polysaccharide and primary immunizations should be administered prior to rituximab infusions to maximize responses.
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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
- Bingham, C. O., Looney, R. J., Deodhar, A., Halsey, N., Greenwald, M., Codding, C., Trzaskoma, B., Martin, F., Agarwal, S., & Kelman, A.
- Affiliations
- Johns Hopkins University (US)
- University of Rochester (US)
- Oregon Health & Science University (US)
- Genentech (US)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2009-12-28
- Volume
- 62
- Issue
- 1
- Pages
- 64-74
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2042927558
- Cited by
- 459
- References
- 37
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 15 · 2023: 27 · 2022: 33 · 2021: 64 · 2020: 33 · 2019: 23 · 2018: 22 · 2017: 35 · 2016: 21 · 2015: 29 · 2014: 28 · 2013: 34 · 2012: 23
- FWCI
- 16.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- rheumatoid arthritis, rituximab, immunization response, vaccine immunogenicity, tetanus toxoid vaccine, pneumococcal polysaccharide vaccine, keyhole limpet hemocyanin, delayed-type hypersensitivity, methotrexate, T cell-independent response
- MeSH terms
- Rituximab, Adolescent, Adult, Aged, Antibodies, Monoclonal, Antibody Formation, Arthritis, Rheumatoid, Drug Therapy, Combination, Female, Hemocyanins, Humans, Hypersensitivity, Delayed, Immunologic Memory, Influenza Vaccines, Lymphocyte Depletion, Male, Methotrexate, Middle Aged, Skin Tests, Tetanus Toxoid, Vaccines, B-Lymphocyte Subsets, Antirheumatic Agents, Lymphocyte Count, Antigens, CD20, Pneumococcal Vaccines, Young Adult, Antibodies, Monoclonal, Murine-Derived
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