Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: Metabolic and immunologic features at baseline identify a subgroup of responders

  1. the AbATE Study Team
  1. Department of Immunobiology and Internal Medicine, Yale University, New Haven, CT (Prof K C Herold MD); Immune Tolerance Network, San Francisco, CA (M R Ehlers MBChB, PhD, Peter H Sayre MD PhD); National Institutes of Allergy and Infectious Diseases, Bethesda, MD (J McNamara MD); Immune Tolerance Network, Bethesda, MD (S Aggarwal PhD, D Phippard PhD); Rho Federal Systems Division, Chapel Hill, NC (K D Boyle MS, L Keyes-Elstein DrPH); University of California San Francisco, San Francisco, CA (Prof S E Gitelman MD, Prof J A Bluestone PhD); Barbara Davis Center, University of Colorado, Aurora, CO (Prof P A Gottlieb MD); Benaroya Research Institute, Seattle, WA (C J Greenbaum MD); and Pacific Northwest Diabetes Research Institute, Seattle, WA (W Hagopian MD PhD)
  1. Corresponding Author: Kevan C. Herold Email: Kevan.herold{at}


Trials of immune therapies in new-onset type 1 diabetes (T1D) have shown success but not all subjects respond and the response duration is limited. Our aim was to determine whether two courses of FcR-nonbinding anti-CD3 mAb, teplizumab, reduces the decline in C-peptide in patients with new-onset T1D two years after disease onset, and we also set out to identify characteristics of responders. We treated 52 subjects with new-onset T1D with teplizumab for 2 weeks at diagnosis and after 1 year in a randomized, open-labeled, controlled trial. In the intention to treat analysis of the primary endpoint, teplizumab-treated patients had a reduced decline in C-peptide at 2 years ((mean, 95% CI) -0.28(-0.36, -0.20) nmol/L) vs. control (-0.46(-0.57, -0.35) nmol/L; p=0.002), a 75% improvement. The most common adverse events were rash, transient upper respiratory infections, headache, and nausea. In a post-hoc analysis, we characterized clinical responders and found that metabolic (HbA1c and insulin use) and immunologic features distinguished this group from non-responders to teplizumab. We conclude that teplizumab treatment preserves insulin production and reduces the use of exogenous insulin in some patients with new-onset T1D. Metabolic and immunologic features at entry can identify a subgroup with robust responses to immune therapy.

  • Received March 4, 2013.
  • Accepted June 25, 2013.

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