1. Antithymocyte globulin therapy for patients with recent-onset type 1 diabetes: 2 year results of a randomised trial.
- Author
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Gitelman, Stephen E, Gitelman, Stephen E, Gottlieb, Peter A, Felner, Eric I, Willi, Steven M, Fisher, Lynda K, Moran, Antoinette, Gottschalk, Michael, Moore, Wayne V, Pinckney, Ashley, Keyes-Elstein, Lynette, Harris, Kristina M, Kanaparthi, Sai, Phippard, Deborah, Ding, Linna, Bluestone, Jeffrey A, Ehlers, Mario R, ITN START Study Team, Gitelman, Stephen E, Gitelman, Stephen E, Gottlieb, Peter A, Felner, Eric I, Willi, Steven M, Fisher, Lynda K, Moran, Antoinette, Gottschalk, Michael, Moore, Wayne V, Pinckney, Ashley, Keyes-Elstein, Lynette, Harris, Kristina M, Kanaparthi, Sai, Phippard, Deborah, Ding, Linna, Bluestone, Jeffrey A, Ehlers, Mario R, and ITN START Study Team
- Abstract
Aims/hypothesisType 1 diabetes results from T cell mediated destruction of beta cells. We conducted a trial of antithymocyte globulin (ATG) in new-onset type 1 diabetes (the Study of Thymoglobulin to ARrest T1D [START] trial). Our goal was to evaluate the longer-term safety and efficacy of ATG in preserving islet function at 2 years.MethodsA multicentre, randomised, double-blind, placebo-controlled trial of 6.5 mg/kg ATG (Thymoglobulin) vs placebo in patients with new-onset type 1 diabetes was conducted at seven university medical centres and one Children's Hospital in the USA. The site-stratified randomisation scheme was computer generated at the data coordinating centre using permuted-blocks of size 3 or 6. Eligible participants were between the ages of 12 and 35, and enrolled within 100 days from diagnosis. Subjects were randomised to 6.5 mg/kg ATG (thymoglobulin) vs placebo in a 2:1 ratio. Participants were blinded, and the study design included two sequential patient-care teams: an unblinded study-drug administration team (for the first 8 weeks), and a blinded diabetes management team (for the remainder of the study). Endpoints assessed at 24 months included meal-stimulated C-peptide AUC, safety and immunological responses.ResultsFifty-eight patients were enrolled; at 2 years, 35 assigned to ATG and 16 to placebo completed the study. The pre-specified endpoints were not met. In post hoc analyses, older patients (age 22-35 years) in the ATG group had significantly greater C-peptide AUCs at 24 months than placebo patients. Using complete preservation of baseline C-peptide at 24 months as threshold, nine of 35 ATG-treated participants (vs 2/16 placebo participants) were classified as responders; nine of 11 responders (67%) were older. All participants reported at least one adverse event (AE), with 1,148 events in the 38 ATG participants vs 415 in the 20 placebo participants; a comparable number of infections were n
- Published
- 2016