Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked,...

Area of Science:

• Immunology
• Endocrinology
• Clinical Trials

Background:

• Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells.
• Inhibiting lymphocyte costimulation has shown promise in preserving beta-cell function in new-onset type 1 diabetes.
• Abatacept is an immune-modulating drug targeting T-cell costimulation.

Purpose of the Study:

• To evaluate if abatacept delays or prevents the progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or diabetes.
• To assess the effects of abatacept on immune and metabolic responses in at-risk individuals.

Main Methods:

• Phase 2, randomized, placebo-controlled, double-masked trial.
• 101 participants received monthly abatacept infusions, 111 received placebo for 12 months.
• Progression endpoint: AGT or type 1 diabetes diagnosis via oral glucose tolerance tests.

Main Results:

• Abatacept did not significantly delay progression to AGT or diabetes (HR 0.702, P=0.11).
• Abatacept treatment led to higher C-peptide responses (P < 0.03).
• Abatacept reduced specific T-cell subsets (ICOS+ PD1+ Tfh, Tregs) and increased naive CD4+ T cells during treatment.

Conclusions:

• One-year abatacept treatment did not significantly delay glucose intolerance progression in at-risk individuals.
• Abatacept impacted immune cell subsets and preserved insulin secretion.
• Costimulation blockade may offer a strategy to modify type 1 diabetes progression.