Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes

作者：Eleanor L. Ramos, Colin Mark Dayan, Lucienne Chatenoud, Zdenĕk Šumnı́k, Kimber M. Simmons, Agnieszka Szypowska, Stephen Eric Gitelman, Laura A. Knecht, Elisabeth Niemoeller, Wei Tian, Kevan C. Herold · 发表于：New England Journal of Medicine · 年份：2023 · DOI：10.1056/nejmoa2308743 · 被引用次数：259 · 研究领域：Diabetes and associated disorders、Diabetes Management and Research、Celiac Disease Research and Management

BACKGROUND: Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown. METHODS: In this phase 3, randomized, placebo-controlled trial, we assessed β-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses. The primary end point was the change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78. The key secondary end points were the insulin doses that were required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events. RESULTS: Patients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least-squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P<0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ sign...