, according to research presented at the annual scientific sessions of the American Diabetes Association.
In this study, 76 first-degree relatives of individuals with type 1 diabetes – who did not themselves have the disease but were considered at high risk because of antibodies and abnormal glucose tolerance tests – were randomized to a single two-week outpatient course of intravenous teplizumab or saline placebo. The patients, of whom 72% were 18 years of age or younger, were followed for a median of 745 days and had twice-yearly oral glucose tolerance testing.
Overall, 43% of the 44 patients who received teplizumab were diagnosed with type 1 diabetes during the course of the study, compared with 72% of the 32 who received the placebo. The treatment was associated with a 59% reduction in the hazard ratio for type 1 diabetes, even after adjusting for age, the results of a second oral glucose-tolerance testing before randomization, or the presence of anti-GAD65 antibodies.
The median time to diagnosis was 48.4 months in the teplizumab group and 24.4 months in the placebo group. The greatest effect was seen in the first year after randomization, during which only 7% of the teplizumab group were diagnosed with type 1 diabetes, compared with 44% of the placebo group. The findings were published simultaneously in the New England Journal of Medicine.
“The delay of progression to type 1 diabetes is of clinical importance, particularly for children, in whom the diagnosis is associated with adverse outcomes, and given the challenges of daily management of the condition,” said Dr. Kevan C. Herold, professor of immunobiology and medicine at Yale University, New Haven, Conn., and coauthors.
There were significantly more adverse events in the teplizumab group, compared with placebo, with three-quarters of the 20 grade 3 adverse events being lymphopenia during the first 30 days. In all but one participant, however, the lymphopenia resolved by day 45. Participants receiving teplizumab also reported a higher incidence of dermatologic adverse events, such as a spontaneously-resolving rash that was experienced by just over one-third of the group.
The researchers also looked for evidence of T-cell unresponsiveness, which has been previously seen in patients with new-onset type 1 diabetes who received treatment with teplizumab. They noted an increase in a particular type of CD8+ T cell associated with T-cell unresponsiveness at months 3 and 6 in participants treated with teplizumab.
Teplizumab is an Fc receptor-nonbinding monoclonal antibody that has been shown to reduce the loss of beta-cell function in patients with type 1 diabetes ().
The study was supported by the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the American Diabetes Association, with the study drug and additional site monitoring provided by MacroGenics. Eight authors declared grants, personal fees, and other support from private industry, with one also declaring income and stock options from MacroGenics.
SOURCE: Herold K et al. NEJM. 2019 Jun 9. doi: 10.1056/NEJMoa1902226*
*Correction, 6/9/2019: An earlier version of this story misstated the doi number for the journal article. The number is 10.1056/NEJMoa1902226.