Efficacy of New-Onset Type 1 Diabetes (T1D) Intervention Trials: Variation in 1-Year Outcomes

Mean 2-hour area under the curve (AUC) C-peptide levels at 1 year remain the primary endpoint for most intervention trials in subjects with new onset T1D. Comparisons of efficacy across T1D intervention trials with positive outcomes remain limited. We performed a cross-trial comparison of the NIH TrialNet sponsored new-onset rituximab, abatacept, low-dose anti-thymocyte globulin (ATG) (2.5mg/kg), and ATG/GCSF trials and the NIH ITN sponsored high-dose ATG (6.5mg/kg), alefacept, and teplizumab trials. One-year study group mean AUC C-peptides were adjusted for baseline C-peptide and age and compared to their internal control to retain individual study effects. To further compare differences in AUC C-peptide across trials, rituximab was used as a reference and percent increase compared to rituximab effect was calculated. Using this methodology, low-dose ATG (164%) and teplizumab (171%) provided for the largest relative improvements in AUC C-peptide. Percent effects over rituximab of the other studies were: high-dose ATG (-43%), alefacept (33%), abatacept (37%) and ATG/GCSF (45%). Despite the limitations of meta-like analyses and the notable differences in control group AUC C-peptides, these data strongly support the notion that low-dose ATG and teplizumab provide for the greatest relative preservation of AUC C-peptide amongst recently completed new onset T1D interventions. Disclosure M.J. Haller: Advisory Panel; Self; Pancreum, SAB Biotherapeutics. M.N. Greco: None. D. Schatz: None. M.A. Atkinson: None. T.M. Brusko: Advisory Panel; Self; Caladrius Biosciences, Inc. Board Member; Self; OneVax, LLC. L.M. Jacobsen: None. K.C. Herold: Consultant; Self; Provention Bio, Roche Pharma. S.E. Gitelman: Advisory Panel; Self; Avortes, Intermountain Therapeutics, Lilly Diabetes, Tolerion, Inc. Research Support; Self; Caladrius Biosciences, Inc., Janssen Research & Development. Other Relationship; Self; Novo Nordisk Inc. J. Krischer: None. B.N. Bundy: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust; National Institutes of Health; JDRF; Sanofi; Amgen Inc.; McJunkin Family Charitable Foundation