Year: 2013
Type: article
Study design: Clinical Trial
Abstract: OBJECTIVE: We previously reported that selective depletion of B-lymphocytes with rituximab, an anti-CD20 monoclonal antibody, slowed decline of β-cell function in recent-onset type 1 diabetes mellitus (T1DM) at 1 year. Subjects were followed further to determine whether there was persistence of effect. RESEARCH DESIGN AND METHODS: Eighty-seven subjects (aged 8-40 years) were randomly assigned to, and 81 received, infusions of rituximab or placebo on days 1, 8, 15, and 22. The primary outcome-baseline-adjusted mean 2-h area under the curve (AUC) serum C-peptide during a mixed-meal tolerance test (MMTT) at 1 year-showed higher C-peptide AUC with rituximab versus placebo. Subjects were further followed with additional MMTTs every 6 months. RESULTS: The rate of decline of C-peptide was parallel between groups but shifted by 8.2 months in rituximab-treated subjects. Over 30 months, AUC, insulin dose, and HbA1c were similar for rituximab and placebo. However, in evaluating change in C-peptide over the entire follow-up period, the rituximab group means were significantly larger as compared within assessment times with the placebo group means using a global test (P = 0.03). Odds ratio for loss of C-peptide to <0.2 nmol/L following rituximab was 0.565 (P = 0.064). B-lymphocytes recovered to baseline values by 18 months. Serum IgG levels were maintained in the normal range but IgM levels were depressed. CONCLUSIONS: Like several other immunotherapeutic approaches tested, in recent-onset T1DM, rituximab delays the fall in C-peptide but does not appear to fundamentally alter the underlying pathophysiology of the disease.
Source: Diabetes Care
DOI: 10.2337/dc13-0626
Authors: Mark D. Pescovitz, Carla J. Greenbaum, Brian Bundy, Dorothy J. Becker, Stephen E. Gitelman, Robin Goland, Peter A. Gottlieb, Jennifer B. Marks, Antoinette Moran, Philip Raskin, Henry Rodriguez, Desmond A. Schatz, Diane K. Wherrett, Darrell M. Wilson, Jeffrey P. Krischer, Jay S. Skyler, the Type 1 Diabetes TrialNet Anti-CD20 Study Group
Institutions: Indiana University School of Medicine, Virginia Mason Medical Center, Benaroya Research Institute, University of South Florida, University of Pittsburgh, University of California, San Francisco, Columbia University, University of Miami, University of Minnesota, The University of Texas Southwestern Medical Center, University of Florida, University of Toronto, Hospital for Sick Children, Stanford University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Funders: American Diabetes Association, Juvenile Diabetes Research Foundation International, Amgen, Eli Lilly and Company, Pfizer, Amylin Pharmaceuticals, AstraZeneca, GlaxoSmithKline, Sanofi, Biogen, Osiris Therapeutics, MannKind Corporation, Halozyme, Dexcom, MacroGenics, Novo Nordisk, National Institutes of Health, Genentech, National Institute of Diabetes and Digestive and Kidney Diseases, U.S. National Library of Medicine, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1, G1132206153, G1134233510, Los Angeles Basin Clinical and Translational Science Institute, UF Clinical and Translational Science Award, UT Southwestern Center for Translational Medicine (UL1/KL2/TL1), Clinical and Translational Science Institute, Type 1 Diabetes TrialNet: Clinical Centers, TrialNet: University of Florida Clinical Center and Network, Type 1 Diabetes TrialNet at Indiana University Clinical Center, Type 1 Diabetes-A Proposal for Prevention & Intervention, CLINICAL AFFILIATE OF THE TYPE 1 DIABETES TRIALNET, GCRC-General Clinical Research Center, G2331704211, Indiana Clinical and Translational Sciences Institute, Type 1 Diabetes Trialnet: Operations Coord. Center, Spectrum Stanford Center for clinical and Translational Research and Education, Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1, Impact of MHC Genotype on Ex Vivo T cell Function in Type 1 Diabetes, Type 1 Diabetes-A Proposal for Prevention & Intervention, Continuation of UCSF as a Clinical Center for TrialNet, G3724172460, University of Pittsburgh Clinical and Translational Science Institute, Prediction and Prevention of Type 1 Diabetes (TrialNet), Northwest Clinical Center for Type 1 Diabetes - TrialNet, North and Central Texas Clinical and Translational Science Initiative (UL1), Indiana Clinical and Translational Science Institute (UL1), University of Pittsburgh Clinical and Translational Science Institute, TrialNet at Stanford University, Colorado Clinical and Translational Sciences Institute, Type 1 Diabetes TrialNet: Toronto Clinical Centre, G653690408, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, G7133194941, Type 1 Diabetes TrialNet: Clinical Centers (U01), Data Coordinating Center for Type 1 Diabetes TrialNet (UC4)USF: TrialNet UC4-3, Type 1 Diabetes TrialNet: Support Facilities, Type 1 diabetes TrialNet Center at Yale University, Indiana Clinical and Translational Sciences Institute, G7975917069, Yale University Clinical and Translational Science Award Program, NIDDK Type 1 Diabetes TrialNet Data Coordinating Center, TrialNet: Diabetes Type 1 Prevention, G871789362, Diabetes Research Center, Diabetes Research Center, Colorado Clinical and Translational Science Institute (UL1)
OpenAlex ID: W2099862791