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Cited by 1,093Diabetes and associated disordersT-cell and B-cell ImmunologyDiabetes Management and Research

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

Rituximab, B-Lymphocyte Depletion, and Preservation of Beta-Cell Function

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Pescovitz, Mark D., Greenbaum, Carla J., Krause-Steinrauf, Heidi, Becker, Dorothy J., Gitelman, Stephen E., Goland, Robin, Gottlieb, Peter A., Marks, Jennifer B., McGee, Paula F., Moran, Antoinette M., Raskin, Philip, Rodriguez, Henry, Schatz, Desmond A., Wherrett, Diane, Wilson, Darrell M., Lachin, John M., Skyler, Jay S.·2009·New England Journal of Medicine
DOI 10.1056/nejmoa0904452PMC PMC6410357
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Abstract

BACKGROUND: The immunopathogenesis of type 1 diabetes mellitus is associated with T-lymphocyte autoimmunity. However, there is growing evidence that B lymphocytes play a role in many T-lymphocyte-mediated diseases. It is possible to achieve selective depletion of B lymphocytes with rituximab, an anti-CD20 monoclonal antibody. This phase 2 study evaluated the role of B-lymphocyte depletion in patients with type 1 diabetes. METHODS: We conducted a randomized, double-blind study in which 87 patients between 8 and 40 years of age who had newly diagnosed type 1 diabetes were assigned to receive infusions of rituximab or placebo on days 1, 8, 15, and 22 of the study. The primary outcome, assessed 1 year after the first infusion, was the geometric mean area under the curve (AUC) for the serum C-peptide level during the first 2 hours of a mixed-meal tolerance test. Secondary outcomes included safety and changes in the glycated hemoglobin level and insulin dose. RESULTS: At 1 year, the mean AUC for the level of C peptide was significantly higher in the rituximab group than in the placebo group. The rituximab group also had significantly lower levels of glycated hemoglobin and required less insulin. Between 3 months and 12 months, the rate of decline in C-peptide levels in the rituximab group was significantly less than that in the placebo group. CD19+ B lymphocytes were depleted in patients in the rituximab group, but levels increased to 69% of baseline values at 12 months. More patients in the rituximab group than in the placebo group had adverse events, mostly grade 1 or grade 2, after the first infusion. The reactions appeared to be minimal with subsequent infusions. There was no increase in infections or neutropenia with rituximab. CONCLUSIONS: A four-dose course of rituximab partially preserved beta-cell function over a period of 1 year in patients with type 1 diabetes. The finding that B lymphocytes contribute to the pathogenesis of type 1 diabetes may open a new pathway for exploration in the treatment of patients with this condition. (ClinicalTrials.gov number, NCT00279305.)

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Metadata

Authors
Pescovitz, M. D., Greenbaum, C. J., Krause-Steinrauf, H., Becker, D. J., Gitelman, S. E., Goland, R., Gottlieb, P. A., Marks, J. B., McGee, P. F., Moran, A. M., Raskin, P., Rodriguez, H., Schatz, D. A., Wherrett, D., Wilson, D. M., Lachin, J. M., & Skyler, J. S.
Affiliations
  • Indiana University School of Medicine (US)
  • Benaroya Research Institute (US)
  • George Washington University (US)
  • University of Pittsburgh (US)
  • University of California, San Francisco (US)
  • Columbia University (US)
  • University of Colorado Health (US)
  • University of Miami (US)
  • University of Minnesota (US)
  • The University of Texas Southwestern Medical Center (US)
  • University of Florida (US)
  • University of Toronto (CA)
  • Stanford University (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2009-11-26
Volume
361
Issue
22
Pages
2143-2152
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa0904452
PMC
PMC6410357
OpenAlex
W2064431167
Cited by
1,093
References
39
Citations by year
2026: 45 · 2025: 65 · 2024: 56 · 2023: 55 · 2022: 56 · 2021: 64 · 2020: 53 · 2019: 49 · 2018: 49 · 2017: 45 · 2016: 57 · 2015: 63 · 2014: 72 · 2013: 98 · 2012: 89
FWCI
51.38
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • Purdue University Indianapolis (Indiana University) (submittedVersion)
  • PMC
Funders
  • American Diabetes Association
  • Juvenile Diabetes Research Foundation International
  • Eli Lilly and Company
  • Biogen
  • Osiris Therapeutics
  • MacroGenics
  • National Institutes of Health
  • Genentech
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Diabetes and Digestive and Kidney Diseases (R21DK077329, U01DK061058, U01DK061034, U01DK103282)
  • National Institute of Child Health and Human Development
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
rituximab, B-cell depletion, type 1 diabetes, beta-cell preservation, anti-CD20 monoclonal antibody, C-peptide, CD19+ B cells, immunopathogenesis, newly diagnosed type 1 diabetes, HbA1c, insulin dose
MeSH terms
Rituximab, Adolescent, Adult, Antibodies, Monoclonal, B-Lymphocytes, C-Peptide, Child, Diabetes Mellitus, Type 1, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Immunoglobulin M, Immunologic Factors, Male, Area Under Curve, Insulin-Secreting Cells, Young Adult, Antibodies, Monoclonal, Murine-Derived

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