Type 1 diabetes (T1D) is a chronic, slowly progressive autoimmune disease characterized by the destruction of β-cells in the pancreas. Although the presence of autoantibodies is a diagnostic criterion, the immunopathogenesis of β-cell destruction in T1D is typically associated with T-lymphocyte autoimmunity. B lymphocytes play a crucial role as antigen-presenting cells in the mechanism of T lymphocyte activation. The Effects of Rituximab on the Progression of Type 1 Diabetes in New Onset Subjects (TN05 antiCD20) is a randomized, placebo-controlled clinical trial that was established by TrialNet, a network of 18 clinical centers that conducts research on T1D, to test whether transient elimination of B lymphocytes with the anti-CD20 monoclonal antibody rituximab would decrease immune-mediated destruction of β-cells and thus preserve β-cell function in patients with T1D of recent onset.

Patients between the ages of 8 and 45 years who had T1D were screened for the presence of at least one type of detectable diabetes autoantibody (microinsulin autoantibody, glutamic acid decarboxylase 65, islet-cell antigen 512, or islet-cell autoantibody). Eligible patients were randomized to treatment with rituximab via intravenous infusion or placebo. The primary outcome measure was the mean area under the curve (AUC) for the stimulated C-peptide response during the first 2 hours of a 4-hour mixed-meal tolerance test conducted at 12 months, with the response expressed in picomoles per milliliter. Safety outcome measures included infusion reactions (occurring within 24 hours after an infusion), infections, and laboratory assessments of white-cell counts and immunoglobulin levels. Patients were followed for an additional year after evaluation of the primary outcome at 12 months.

Results showed that the mean AUC for the level of C peptide was significantly higher for the rituximab group than for the placebo group at 12 months. Additionally, the glycated hemoglobin level and the insulin dose were both significantly lower in the treatment group than in the placebo group. The group treated with rituximab showed higher rates of adverse events. Findings support the hypothesis that B lymphocytes play a role in the pathogenesis of T1D and that therapy targeting B cells may have a beneficial effect on β-cell function in early T1D. While initial improvements in C-peptide levels following rituximab administration resumed decline after 12 months, treatment with other anti-B-lymphocyte agents may open a new pathway for exploration in the treatment of patients with this condition.

This study sought to determine to whether transient elimination of B lymphocytes with the anti-CD20 monoclonal antibody rituximab would decrease immune-mediated destruction of β-cells and thus preserve β-cell function in patients with T1D of recent onset.

The primary outcome measure was the mean area under the curve (AUC) for the stimulated C-peptide response during the first 2 hours of a 4-hour mixed-meal tolerance test conducted at 12 months, with the response expressed in picomoles per milliliter. Safety outcome measures included infusion reactions (occurring within 24 hours after an infusion), infections, and laboratory assessments of white-cell counts and immunoglobulin levels.

Patients between the ages of 8 and 45 years who met the following criteria were eligible for enrollment:

• Diagnosis of type 1 diabetes within 3 months
• Presence of at least one diabetes-related antibody (microinsulin autoantibody, glutamic acid decarboxylase 65, islet-cell antigen 512, or islet-cell autoantibody)
• Stimulated C-peptide levels of at least 0.2 pmol/ml measure during a mixed meal tolerance test within one month of randomization
• Had not received an immunization for at least 1 month

Exclusion criteria are documented in the study protocol.

Results showed that the mean AUC for the level of C peptide was significantly higher for the rituximab group than for the placebo group at 12 months. Additionally, the glycated hemoglobin level and the insulin dose were both significantly lower in the treatment group than in the placebo group. These findings support the hypothesis that B lymphocytes play a role in the pathogenesis of T1D and that therapy targeting B cells may have a beneficial effect on β-cell function in early T1D. While initial improvements in C-peptide levels following rituximab administration resumed decline after 12 months, treatment with other anti-B-lymphocyte agents may open a new pathway for exploration in the treatment of patients with this condition.