Generalizability of progression risk in the TN-10 trial to a European population with or without a first-degree relative with type 1 diabetes

<p dir="ltr"><b>Objective</b></p><p dir="ltr">In the TrialNet 10 (TN-10) trial, teplizumab delayed onset of stage 3 type 1 diabetes in US and Canadian individuals with stage 2 disease who had a relative with type 1 diabetes. Here, the generalizability of the population risk in TN-10 to a European population with or without first-degree relatives (FDRs) with type 1 diabetes was investigated.</p><p dir="ltr"><b>Research Design and Methods</b></p><p dir="ltr">This retrospective study used data from participants with stage 2 type 1 diabetes from the TN-10 placebo arm and the Fr1da population-based screening program in Germany (Fr1da group) to investigate time to progression from stage 2 to 3 type 1 diabetes. The study only had sufficient power to detect large differences.</p><p dir="ltr"><b>Results</b></p><p dir="ltr"><a href="" target="_blank">Risk of progression to stage 3 type 1 diabetes was comparable between the TN-10 placebo arm (n=32) and the Fr1da group (n=152; HR=1.3 [95% CI: 0.8-2.1]). </a>Once prognostic factors significantly associated with progression in this study (anti-IA-2 antibodies, HbA1c >5.7%, and 120-minute OGTT) were included in the model, the adjusted HR was 1.1 (95% CI: 0.6-2.1). Fr1da group participants with (n=45) and without (n=107) FDRs with type 1 diabetes had similar time to progression to stage 3. Age-based subanalysis demonstrated minimal impact of age on progression time.</p><p dir="ltr"><b>Conclusions</b></p><p dir="ltr">Time to progression to stage 3 appeared similar between the TN-10 placebo arm and the Fr1da group and between participants with and without FDRs with disease. Results suggest progression risk from the TN-10 trial may be generalizable to European populations with or without FDRs with type 1 diabetes.</p>