ATG_GCSF_5Yr_Supplement_R1_AL_alp_clean.pdf (517.32 kB)
Download fileLow-dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report
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posted on 2021-02-26, 00:11 authored by Andrea Lin, Jasmine A. Mack, Brittany Bruggeman, Laura M. Jacobsen, Amanda L. Posgai, Clive H. Wasserfall, Todd M. Brusko, Mark A. Atkinson, Stephen E. Gitelman, Peter A. Gottlieb, Matthew J. Gurka, Clayton E. Mathews, Desmond A Schatz, Michael J. HallerPreviously, we demonstrated low-dose anti-thymocyte
globulin (ATG) and granulocyte colony stimulating factor (GCSF) immunotherapy preserved
C-peptide for two years in a pilot study of subjects with established type 1
diabetes (n=25). Herein, we evaluated the long-term outcomes of ATG/GCSF in
study participants with five years of available follow-up data (n=15). The
primary endpoint was area under the curve (AUC) C-peptide during a two-hour
mixed-meal tolerance test (MMTT). After five years, there were no statistically significant
differences in AUC C-peptide when comparing subjects who received ATG/GCSF versus
placebo (p = 0.41). A modeling
framework based on mean trajectories in C-peptide AUC over five years, accounting
for differing trends between groups, was applied to re-categorize responders
(n=9) and non-responders (n=7). ATG/GCSF reponders demonstrated nearly
unchanged HbA1c over five years [mean (95% CI) adjusted change = 0.29% (-0.69%, 1.27%)], but the study was not powered for
comparisons against non-responders 1.75% (-0.57%, 4.06%) and placebo 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.