The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis
Open accessAbstract
BACKGROUND: An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis. To confirm these observations, we conducted a randomized, double-blind, controlled study. METHODS: We randomly assigned 161 patients who had active rheumatoid arthritis despite treatment with methotrexate to receive one of four treatments: oral methotrexate (> or =10 mg per week) (control); rituximab (1000 mg on days 1 and 15); rituximab plus cyclophosphamide (750 mg on days 3 and 17); or rituximab plus methotrexate. Responses defined according to the criteria of the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) were assessed at week 24 (primary analyses) and week 48 (exploratory analyses). RESULTS: At week 24, the proportion of patients with 50 percent improvement in disease symptoms according to the ACR criteria, the primary end point, was significantly greater with the rituximab-methotrexate combination (43 percent, P=0.005) and the rituximab-cyclophosphamide combination (41 percent, P=0.005) than with methotrexate alone (13 percent). In all groups treated with rituximab, a significantly higher proportion of patients had a 20 percent improvement in disease symptoms according to the ACR criteria (65 to 76 percent vs. 38 percent, P< or =0.025) or had EULAR responses (83 to 85 percent vs. 50 percent, P< or =0.004). All ACR responses were maintained at week 48 in the rituximab-methotrexate group. The majority of adverse events occurred with the first rituximab infusion: at 24 weeks, serious infections occurred in one patient (2.5 percent) in the control group and in four patients (3.3 percent) in the rituximab groups. Peripheral-blood immunoglobulin concentrations remained within normal ranges. CONCLUSIONS: In patients with active rheumatoid arthritis despite methotrexate treatment, a single course of two infusions of rituximab, alone or in combination with either cyclophosphamide or continued methotrexate, provided significant improvement in disease symptoms at both weeks 24 and 48.
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“In humans, a reversible depletion of normal B cells is a well-tolerated side effect of the anti-CD20 antibody rituximab, which is an efficacious therapy in mature B cell neoplasms and in autoimmune disease”
From The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer (2015) · cites this paper as Edwards et al., 2004
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Measurement of patient outcome in arthritis
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Cytokine Pathways and Joint Inflammation in Rheumatoid Arthritis
Choy, E., & Panayi, G. S. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103223441207 · Cited by 2,248
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T Cell Activation in Rheumatoid Synovium Is B Cell Dependent
Takemura, S., Klimiuk, P. A., Braun, A. B., Goronzy, J. J., & Weyand, C. M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.8.4710 · Cited by 536
Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes
Edwards, J., & Cambridge, G. (2001) · Lara D. Veeken · doi:10.1093/rheumatology/40.2.205 · Cited by 525
Self-citationClinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion
Leandro, M. J., Edwards, J. C. W., & Cambridge, G. (2002) · Annals of the Rheumatic Diseases · doi:10.1136/ard.61.10.883 · Cited by 344
Self-citationvan Gestel, A. M., Anderson, J. J., van Riel, P. L. C. M., Boers, M., HAAGSMA, C. J., Rich, B., Wells, G. A., Lange, M., & Felson, D. T. (1999) · PubMed · Cited by 250
Do self‐perpetuating B lymphocytes drive human autoimmune disease?
Edwards, E., Cambridge, & Abrahams (1999) · Immunology · doi:10.1046/j.1365-2567.1999.00772.x · Cited by 174
The role of B cells in rheumatoid arthritis
Dörner, T., & Burmester, G. R. (2003) · Current Opinion in Rheumatology · doi:10.1097/00002281-200305000-00011 · Cited by 164
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Smolen, J. S., Landewé, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M., Nam, J., Ramiro, S., Voshaar, M., van Vollenhoven, R., et al. (2017) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-210715 · Cited by 2,057
Self-citationThe Pathogenesis of Rheumatoid Arthritis
McInnes, I. B., & Schett, G. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1004965 · Cited by 5,514
Cytokines in the pathogenesis of rheumatoid arthritis
McInnes, I. B., & Schett, G. A. (2007) · Nature reviews. Immunology · doi:10.1038/nri2094 · Cited by 2,576
Paradoxical roles of the immune system during cancer development
de Visser, K. E., Eichten, A., & Coussens, L. M. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1782 · Cited by 2,299
Rituximab versus Cyclophosphamide in ANCA-Associated Renal Vasculitis
Jones, R. B., Tervaert, J. W. C., Hauser, T., Luqmani, R. A., Morgan, M. D., Peh, C. A., Savage, C. O. S., Segelmark, M., Tesař, V., van Paassen, P., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0909169 · Cited by 1,744
Metadata
- Authors
- Edwards, J. C. W., Szczepański, L., Szechiński, J., Filipowicz-Sosnowska, A., Emery, P., Close, D. R., Stevens, R. M., & Shaw, T.
- Affiliations
- University College London (GB)
- University of Wrocław (PL)
- Roche (United Kingdom) (GB)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2004-06-17
- Volume
- 350
- Issue
- 25
- Pages
- 2572-2581
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2118994799
- Cited by
- 2,623
- References
- 21
- Citations by year
- 2026: 65 · 2025: 69 · 2024: 76 · 2023: 62 · 2022: 61 · 2021: 85 · 2020: 87 · 2019: 85 · 2018: 103 · 2017: 112 · 2016: 96 · 2015: 103 · 2014: 129 · 2013: 133 · 2012: 133
- FWCI
- 109.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- rheumatoid arthritis, rituximab, B-cell depletion, cyclophosphamide, methotrexate, combination therapy, adverse events, serious infections, immunoglobulin levels, treatment-resistant rheumatoid arthritis, ACR response criteria, EULAR response criteria, maintenance therapy, relapse prevention, long-term follow-up, drug efficacy
- MeSH terms
- Rituximab, Antibodies, Monoclonal, Arthritis, Rheumatoid, B-Lymphocytes, Bacterial Infections, Cyclophosphamide, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Immunosuppressive Agents, Male, Methotrexate, Middle Aged, Antirheumatic Agents, Antigens, CD20, Antibodies, Monoclonal, Murine-Derived
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