Low-Dose ATG/GCSF in Established Type 1 Diabetes

A Five-Year Follow-up Report

Lin, Andrea
Mack, Jasmine A.
Bruggeman, Brittany
Jacobsen, Laura M.
Posgai, Amanda L.
Wasserfall, Clive H.
Brusko, Todd M.
Atkinson, Mark A.
Gitelman, Stephen E.
Gottlieb, Peter A.
Gurka, Matthew J.
Mathews, Clayton E.
Schatz, Desmond A.
Haller, Michael J.

¹Department of Pathology, Immunology, and Laboratory Medicine, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL
²Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainesville, FL
³Department of Pediatrics, Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL
⁴Division of Endocrinology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA
⁵Division of Endocrinology, Department of Pediatrics and Medicine, University of Colorado, Denver, CO

Corresponding author: Michael J. Haller, [email protected]

Received October 30, 2020

Accepted February 23, 2021

Diabetes 70(5):p 1123-1129, May 2021. | DOI: 10.2337/db20-1103

Previously, we demonstrated low-dose antithymocyte globulin (ATG) and granulocyte colony-stimulating factor (GCSF) immunotherapy preserved C-peptide for 2 years in a pilot study of patients with established type 1 diabetes (n = 25). Here, we evaluated the long-term outcomes of ATG/GCSF in study participants with 5 years of available follow-up data (n = 15). The primary end point was area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test. After 5 years, there were no statistically significant differences in AUC C-peptide when comparing those who received ATG/GCSF versus placebo (P = 0.41). A modeling framework based on mean trajectories in C-peptide AUC over 5 years, accounting for differing trends between groups, was applied to recategorize responders (n = 9) and nonresponders (n = 7). ATG/GCSF reponders demonstrated nearly unchanged HbA_1c over 5 years (mean [95% CI] adjusted change 0.29% [–0.69%, 1.27%]), but the study was not powered for comparisons against nonresponders 1.75% (–0.57%, 4.06%) or placebo recipients 1.44% (0.21%, 2.66%). These data underscore the importance of long-term follow-up in previous and ongoing phase 2 trials of low-dose ATG in recent-onset type 1 diabetes.