Rituximab, B-lymphocyte depletion, and preservation of beta-cell function
dc.contributor.author | Pescovitz, Mark D. | |
dc.contributor.author | Greenbaum, Carla J. | |
dc.contributor.author | Krause-Steinrauf, Heidi | |
dc.contributor.author | Becker, Dorothy J. | |
dc.contributor.author | Gitelman, Stephen E. | |
dc.contributor.author | Goland, Robin | |
dc.contributor.author | Gottlieb, Peter A. | |
dc.contributor.author | Marks, Jennifer B. | |
dc.contributor.author | McGee, Paula F. | |
dc.contributor.author | Moran, Antoinette M. | |
dc.contributor.author | Raskin, Philip | |
dc.contributor.author | Rodriguez, Henry | |
dc.contributor.author | Schatz, Desmond A. | |
dc.contributor.author | Wherrett, Diane | |
dc.contributor.author | Wilson, Darrell M. | |
dc.contributor.author | Lachin, John M. | |
dc.contributor.author | Skyler, Jay S. | |
dc.contributor.author | Type 1 Diabetes TrialNet Anti-CD20 Study Group | |
dc.contributor.department | Medicine, School of Medicine | en_US |
dc.date.accessioned | 2019-08-07T20:29:13Z | |
dc.date.available | 2019-08-07T20:29:13Z | |
dc.date.issued | 2009-11-26 | |
dc.description.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. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Pescovitz, M. D., Greenbaum, C. J., Krause-Steinrauf, H., Becker, D. J., Gitelman, S. E., Goland, R., … Type 1 Diabetes TrialNet Anti-CD20 Study Group (2009). Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. The New England journal of medicine, 361(22), 2143–2152. doi:10.1056/NEJMoa0904452 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/20241 | |
dc.language.iso | en_US | en_US |
dc.publisher | Massachusetts Medical Society | en_US |
dc.relation.isversionof | 10.1056/NEJMoa0904452 | en_US |
dc.relation.journal | New England Journal of Medicine | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Rituximab | en_US |
dc.subject | Antibodies, Monoclonal | en_US |
dc.subject | Area Under Curve | en_US |
dc.subject | B-Lymphocytes | en_US |
dc.subject | C-Peptide | en_US |
dc.subject | Diabetes Mellitus, Type 1 | en_US |
dc.subject | Double-Blind Method | en_US |
dc.subject | Glycated Hemoglobin A | en_US |
dc.subject | Immunoglobulin M | en_US |
dc.subject | Immunologic Factors | en_US |
dc.subject | Insulin-Secreting Cells | en_US |
dc.subject | Humans | en_US |
dc.title | Rituximab, B-lymphocyte depletion, and preservation of beta-cell function | en_US |
dc.type | Article | en_US |