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. 2020 Dec;22(12):948-953.
doi: 10.1089/dia.2020.0305. Epub 2020 Oct 20.

Comparing Beta Cell Preservation Across Clinical Trials in Recent-Onset Type 1 Diabetes

Laura M Jacobsen  1 , Brian N Bundy  2 , Madison N Greco  1 , Desmond A Schatz  1 , Mark A Atkinson  3 , Todd M Brusko  3 , Clayton E Mathews  3 , Kevan C Herold  4 , Stephen E Gitelman  5 , Jeffrey P Krischer  2 , Michael J Haller  1
Affiliations

Comparing Beta Cell Preservation Across Clinical Trials in Recent-Onset Type 1 Diabetes

Laura M Jacobsen et al. Diabetes Technol Ther. 2020 Dec.

Abstract

Several immunotherapies have demonstrated endogenous insulin preservation in recent-onset type 1 diabetes (T1D). We considered the primary results of rituximab, abatacept, teplizumab, alefacept, high-dose antithymocyte globulin (ATG), low-dose ATG, and low-dose ATG ± granulocyte-colony-stimulating factor trials in an attempt to rank the effectiveness of the agents studied. C-peptide 2-h area under the curve means were modeled using analysis of covariance. The experimental treatment group effect for each study, compared with its internal control, was estimated after adjusting for baseline C-peptide and age. Percentage increase in C-peptide over placebo and the absolute difference within study were calculated to compare and contrast effect size among interventions. Low-dose ATG (55% and 103%) and teplizumab (48% and 63%) ranked highest in C-peptide preservation at 1 and 2 years, respectively. Low-dose ATG and teplizumab show the greatest impact on C-peptide preservation among recent new-onset T1D studies; these should be further explored as core immunotherapies in the T1D prevention setting.

Keywords: Clinical trial; Immunotherapy; Intervention; Type 1 diabetes.

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Conflict of interest statement

M.J.H. is on the scientific advisory board of SAb Biotherapeutics and received grant funding from Sanofi, and The Helmsley Charitable Trust to perform studies of low-dose ATG. MAA holds a patent on ATG plus G-CSF for the treatment of type 1 diabetes. There are no other conflicts of interest to disclose.

Figures

FIG. 1.
FIG. 1.
Cross-trial comparison of recent-onset T1D intervention trials. (A) One-year and (C) 2-year percentage increase in C-peptide between placebo and experiment groups comparing C-peptide AUC means (with 95% confidence intervals) from six recent-onset T1D studies adjusted for baseline AUC C-peptide and age with study effect retained. (B) One-year and (D) 2-year absolute C-peptide difference presented as a point estimate with 95% confidence intervals. The low-dose ATG and ATG/G-CSF study arms are presented separately. The number of subjects with available data per study is listed at the bottom of (A) and (C). ATG, antithymocyte globulin; AUC, area under the curve; G-CSF, granulocyte-colony–stimulating factor; T1D, type 1 diabetes.
FIG. 1.
FIG. 1.
Cross-trial comparison of recent-onset T1D intervention trials. (A) One-year and (C) 2-year percentage increase in C-peptide between placebo and experiment groups comparing C-peptide AUC means (with 95% confidence intervals) from six recent-onset T1D studies adjusted for baseline AUC C-peptide and age with study effect retained. (B) One-year and (D) 2-year absolute C-peptide difference presented as a point estimate with 95% confidence intervals. The low-dose ATG and ATG/G-CSF study arms are presented separately. The number of subjects with available data per study is listed at the bottom of (A) and (C). ATG, antithymocyte globulin; AUC, area under the curve; G-CSF, granulocyte-colony–stimulating factor; T1D, type 1 diabetes.
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References

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