Pescovitz, Mark D.Greenbaum, Carla J.Krause-Steinrauf, HeidiBecker, Dorothy J.Gitelman, Stephen E.Goland, RobinGottlieb, Peter A.Marks, Jennifer B.McGee, Paula F.Moran, Antoinette M.Raskin, PhilipRodriguez, HenrySchatz, Desmond A.Wherrett, DianeWilson, Darrell M.Lachin, John M.Skyler, Jay S.Type 1 Diabetes TrialNet Anti-CD20 Study Group2019-08-072019-08-072009-11-26Pescovitz, 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/NEJMoa0904452https://hdl.handle.net/1805/20241BACKGROUND: 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-USPublisher PolicyRituximabAntibodies, MonoclonalArea Under CurveB-LymphocytesC-PeptideDiabetes Mellitus, Type 1Double-Blind MethodGlycated Hemoglobin AImmunoglobulin MImmunologic FactorsInsulin-Secreting CellsHumansArticle