731-P: The Effect of Abatacept upon Glucose and C-Peptide Endpoints at One Year of Treatment and on Follow-up

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The TrialNet abatacept randomized-controlled trial tested for the ability to delay the progression of T1D in Stage 1 [multiple autoantibody (Ab) positive and normal glucose on OGTT] individuals aged 6-45. No drug effect was detected on the primary endpoint of either dysglycemia or T1D (whichever came first). Based on evidence that C-peptide-based metabolic measures are more specific for T1D and detect an early impact of disease-modifying therapy, we performed post-hoc analyses using these variables and stratified on baseline metabolic profiles. In participants with lower baseline metabolic risk (Index60 <0.00) we assessed if changes in metabolic measures would differ between treatment groups. A favorable effect was evident for the combined glucose and C-peptide endpoints within 1 year of treatment (Table). Next we compared individuals with Index60<0.00 at baseline for exceeding an Index60 threshold of 1.00 on follow-up. 5-year risks were 38.9% for the placebo and 21.1% for the abatacept groups (p=0.016). In summary, for Stage 1 individuals with low baseline metabolic risk, combined glucose and C-peptide endpoints can detect a favorable abatacept effect at 1 year and, more conventionally, a decreased T1D progression risk on follow-up. Future trials of abatacept or other agents in Stage 1 T1D should include combined glucose and C-peptide measures as pre-specified endpoints. Disclosure E.K.Sims: Speaker's Bureau; Medscape, American Diabetes Association. W.E.Russell: None. K.C.Herold: Board Member; NexImmune, Consultant; Provention Bio, Inc. J.Sosenko: None.