Co-Stimulation Modulation With Abatacept in Patients With Recent-Onset Type 1 Diabetes: A Randomised, Double-Blind, Placebo-Controlled Trial
Does modulation of T-cell activation with abatacept in patients with type 1 diabetes mellitus (DM) lead to preservation of pancreatic β-cell function?
Patients ages 6-45 years recently diagnosed with type 1 diabetes were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1000 mg per dose) or placebo infusions intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years. The primary outcome was 2-hour area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal tolerance test at 2-year follow-up.
A total of 112 patients were assigned to treatment groups (77 abatacept, 35 placebo). Adjusted C-peptide AUC was 59% higher at 2 years with abatacept (0.378 nmol/L) than with placebo (0.238 nmol/L; p = 0.0029). The difference between groups was present throughout the trial, with an estimated 9.6-month delay in C-peptide reduction with abatacept.
The authors concluded that co-stimulation modulation with abatacept slowed reduction in β-cell function over 2 years. The beneficial effect suggests that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes.
Type 1 diabetes is typically due to autoimmune-mediated destruction of pancreatic β-cells. Preservation of residual β-cell function at the time of diagnosis could reduce diabetic complications. Thus, therapies to reduce the autoimmune response may benefit patients with type 1 diabetes. Abatacept is a fusion protein composed of an immunoglobulin fused to the extracellular domain of cytotoxic T-lymphocyte antigen 4. It inhibits the co-stimulation of T-cells and has been shown to be beneficial in some rheumatologic diseases and to prevent diabetes in a mouse model. This study suggests that there are ongoing T-cell-mediated effects on β-cell function at the time of type 1 DM diagnosis and that insulin secretion can be preserved if these effects are blocked. Whether the apparent early benefit of this treatment on β-cell function will translate into meaningful long-term benefits will require additional studies.
Keywords: Diabetes Complications, Follow-Up Studies, Immunoconjugates, T-Lymphocytes, Diabetes Mellitus, Type 1, CTLA-4 Antigen
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