An anti-CD3 Antibody, Teplizumab, in relatives at risk for type 1 diabetes

HEROLD, KC; Bundy, BN; Long, SA; Bluestone, JA; DiMeglio, LA; Dufort, MJ; Gitelman, SE; Gottlieb, PA; Krischer, JP; Linsley, PS; Marks, JB; Moore, W; Moran, A; Rodriguez, H; Russell, WE; Schatz, D; Skyler, JS; Tsalikian, E; Wherrett, DK; ZIEGLER, AG; Greenbaum, CJ; Type 1 Diabetes TrialNet Study Group,; includes Wentworth, JM

Author(s): HEROLD, KC; Bundy, BN; Long, SA; Bluestone, JA; DiMeglio, LA; Dufort, MJ; Gitelman, SE; Gottlieb, PA; Krischer, JP; Linsley, PS; Marks, JB; Moore, W; Moran, A; Rodriguez, H; Russell, WE; Schatz, D; Skyler, JS; Tsalikian, E; Wherrett, DK; ZIEGLER, AG; Greenbaum, CJ; Type 1 Diabetes TrialNet Study Group,; includes Wentworth, JM;
Details: Publication Year 2019-08,Volume 38,Issue #7,Page 603-613
Journal Title: New England Journal of Medicine
Publication Type: Journal Article
Abstract: BACKGROUND: Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed. METHODS: We conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals. RESULTS: A total of 76 participants (55 [72%] of whom were </=18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. TIGIT+KLRG1+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed. CONCLUSIONS: Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.).
Publisher: Massachusetts Medical Society
Research Division(s): Population Health And Immunity
PubMed ID: 31180194
Publisher's Version: https://doi.org/10.1056/NEJMoa1902226
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2019-06-20 10:18:09

Last Modified: 2019-08-23 02:38:13