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
- Kevan C. Herold1⇑,
- Stephen E. Gitelman2,
- Mario R. Ehlers3,
- Peter A. Gottlieb4,
- Carla J. Greenbaum5,
- William Hagopian6,
- Karen D. Boyle7,
- Lynette Keyes-Elstein7,
- Sudeepta Aggarwal8,
- Deborah Phippard8,
- Peter H. Sayre3,
- James McNamara9,
- Jeffrey A. Bluestone2,
- and the AbATE Study Team*
- 1Department of Immunobiology and Internal Medicine, Yale University, New Haven, Connecticut
- 2Department of Pediatrics, University of California, San Francisco, San Francisco, California
- 3Immune Tolerance Network, San Francisco, California
- 4Department of Pediatrics and Medicine, Barbara Davis Center, University of Colorado, Aurora, Colorado
- 5Benaroya Research Institute, Seattle, Washington
- 6Pacific Northwest Diabetes Research Institute, Seattle, Washington
- 7Rho Federal Systems Division, Chapel Hill, North Carolina
- 8Immune Tolerance Network, Bethesda, Maryland
- 9National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
- Corresponding author: Kevan C. Herold, .
Trials of immune therapies in new-onset type 1 diabetes (T1D) have shown success, but not all subjects respond, and the duration of response is limited. Our aim was to determine whether two courses of teplizumab, an Fc receptor–nonbinding anti-CD3 monoclonal antibody, reduces the decline in C-peptide levels in patients with T1D 2 years after disease onset. 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 an open-label, randomized, controlled trial. In the intent to treat analysis of the primary end point, patients treated with teplizumab had a reduced decline in C-peptide at 2 years (mean −0.28 nmol/L [95% CI −0.36 to −0.20]) versus control (mean −0.46 nmol/L [95% CI −0.57 to −0.35]; 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 those who did not respond 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 baseline can identify a subgroup with robust responses to immune therapy.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0345/-/DC1.
* A list of other members of the AbATE Study Team can be found in the appendix.
See accompanying commentary, p. 3656.
- Received March 4, 2013.
- Accepted June 26, 2013.
- © 2013 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.