In type 1 diabetes, autoimmunity destroys the insulin-producing β-cells in the pancreas. The T-cells of the immune system require a co-stimulating signal to be fully active, and thus interventions to prevent this co-stimulation could prevent further β-cell loss in recently diagnosed type 1 diabetes patients. A study published Online First by The Lancet shows that abatacept helps modulate this co-stimulation and slows β-cell loss, but only for the first six months of treatment. The study is by Dr Jay S Skyler, Diabetes Research Institute, University of Miami Miller School of Medicine, FL, USA, and colleagues from the Type 1 Diabetes TrialNet Abatacept Study Group.
In this trial, patients aged 6 years recently diagnosed with type 1 diabetes were randomly assigned to receive abatacept (10 mg/kg, maximum 1000 mg per dose) (77 patients) or placebo (35 patients) intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years. The effect of the intervention was measured by analysing post-meal blood concentrations of C-peptide, a compound that indicates how many functioning β-cells remain. Adjusted C-peptide levels were 59% higher at 2 years with abatacept than with placebo. However, this difference was attained in the first six months of treatment, with both groups showing similar rates of decline in functioning β-cell mass after this point.
The authors say: "The beneficial effect suggests that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes. Yet, despite continued administration of abatacept over 24 months, the decrease in β-cell function with abatacept was parallel to that with placebo after 6 months of treatment, causing us to speculate that T-cell activation lessens with time. Further observation will establish whether the beneficial effect continues after cessation of abatacept infusions. "
They add: "Abatacept has characteristics that support it as a potential candidate for testing in a prevention trial. Abatacept would also seem to be a candidate as a useful component of a combination therapy protocol in recent-onset type 1 diabetes. These approaches might be more easily tested with a subcutaneous version of abatacept, which is currently in development… Until further studies are done, use of abatacept in type 1 diabetes in clinical practice is not appropriate."
In a linked Comment, Dr Bart O Roep, Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Netherlands, says that the study "underscores that the future treatment of type 1 diabetes will probably involve immunotherapy, supplementary to treatment of insulin deficiency."
Dr Jay S Skyler, Diabetes Research Institute, University of Miami Miller School of Medicine, FL, USA. Please e-mail first to arrange interview. T) +1 305-588-4447 E) jskyler@miami.edu
Dr Bart O Roep, Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Netherlands. T) +31 71 526 3800 E) boroep@lumc.nl
Journal
The Lancet