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Low-dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report

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posted on 26.02.2021, 00:11 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. Haller
Previously, 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.

Funding

This work was supported by The Leona M. and Harry B. Helmsley Charitable Trust (09PG-T1D022), the NIH NIAID (P01-AI042288), NIH NIDDK (T32 DK108736), NIH UF-CTSI (1UL1TR000064), NIH UCSF-CTSI (UL1TR000004), NIH U.Colorado-CTSI (UL1TR001082), and the McJunkin Family Charitable Foundation. Sanofi-Genzyme provided Thymoglobulin® (ATG) for this study free of charge. Amgen, Inc. provided Neulasta® (GCSF) and placebo for the study.

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