• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that is driven by activated T-lymphocytes. To be fully active, immune T-cells need a costimulatory signal in addition to the main antigen-driven signal. A previous study showed that abatacept, a costimulation modulator that prevents full T-cell activation, slowed reduction in β-cell function over 2 years in individuals with recent-onset T1DM [Orban T et al. Lancet 2011]. Tihamer Orban, MD, Joslin Diabetes Center, Boston, Massachusetts, USA, presented 1-year follow-up data from the previous 2-year study [NCT00505375].

The primary study was a multicenter, double-blind, randomized, controlled trial in which subjects (n=112) aged 6 to 45 years (mean 14 years) who were recently diagnosed with T1DM were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1000 mg per dose) or placebo infusions intravenously on Days 1, 14, and 28 and monthly thereafter for a total of 27 infusions over 2 years. Dr. Orban reported on the effects of discontinuing costimulation modulation with abatacept on preservation of β-cell function in patients from this study who were followed for 1 year after infusions were stopped.

The follow-up analysis included 93 subjects (64 from the abatacept group and 29 from the placebo group). C-peptide 2-hour AUC means, adjusted for age and baseline C-peptide, at 36 months were 0.215 (95% CI, 0.168 to 0.265) and 0.135 (95% CI, 0.0692 to 0.205) nmol/L for the abatacept and the placebo groups, respectively (p=0.033). This difference was similar to the difference observed during the treatment phase of the trial. The C-peptide decline from baseline remained parallel with an estimated 9.5-month delay with abatacept. HbA1C was lower in abatacept-treated patients (p<0.001), with no difference in insulin use. A treatment effect was observed only for race and CDR3 status.

Data from this follow-up study indicate that costimulation modulation with abatacept slows the decline in β-cell function in recent-onset T1DM beyond drug administration and leads to lower HbA1C levels. These results suggest that abatacept may be useful in prevention studies in individuals who are at high risk of T1DM and/or as a component in studies that use a combination of different treatment strategies. Further trials are needed to test whether or not a shorter course of abatacept treatment would be sufficient to achieve similar beneficial effects.

• © 2012 MD Conference Express®