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

OBJECTIVEPrevious studies showed that inhibiting lymphocyte costimulation reduces declining & beta;-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses. RESEARCH DESIGN AND METHODSWe conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests. RESULTSA total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)(+) PD1(+) T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4(+) T cells, and also reduced the frequency of CD4(+) regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4(+) T cells, and Tregs returned to baseline. CONCLUSIONSAlthough abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.

Automated summary

This study shows that inhibiting lymphocyte costimulation can reduce the decline in beta-cell function in newly diagnosed type 1 diabetes patients. By treating antibody-positive individuals with normal glucose tolerance with abatacept for 12 months, it was found that abatacept can delay or prevent the progression of type 1 diabetes and affect immune and metabolic responses.