Teplizumab Delays Type 1 Diabetes Onset

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Patients who are at high-risk of developing type 1 diabetes may be able to delay the progression of the condition with teplizumab treatment, a new study shows.

The study, published in the New England Journal of Medicine on June 9, was a phase 2, randomized, placebo-controlled, double-blind trial of 76 patients  who were 18 years old or younger. The patients did not have diabetes, but were genetically susceptible to the condition and had other high-risk features. Patients can live with the condition for years without showing symptoms.

Patients were randomly assigned to a single 14-day course of teplizumab or placebo.
In this trial, 44 patients  (half of whom were siblings of patients with type 1 diabetes) were randomly assigned to teplizumab for a 14-day course and 32 received a placebo. The 76 participants––nearly three-quarters of whom were under 18 years old––were given oral glucose-tolerance tests three and six months after infusions, and then every six months, to test for T1D.
Follow-ups were conducted at six-month intervals through four years. By the end of the trial, 57 percent of those assigned to teplizumab were T1D-free, versus 28 percent of those on placebo.

The findings were as follows:

• 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.
• 19 (43%) of the patients who received teplizumab were diagnosed with type 1 diabetes compared to 23 (72%) in the placebo group.
• The median delay in the diagnosis of diabetes was 2 years.

The onset of diabetes was also different between the two groups––for the placebo group, it took an average of 24.2 months until T1D was diagnosed, while for the teplizumab group, it took an average of 48.4 months to receive a diagnosis. Study authors say that the first year of taking teplizumab showed the strongest results: “...diabetes was diagnosed in only 3 of 44 participants (7%) in the teplizumab group, in contrast to 14 of 32 participants (44%) in the placebo group.”

“In this phase 2 trial, a single course of teplizumab significantly slowed progression to clinical type 1 diabetes in high-risk, nondiabetic relatives of patients with diabetes and had at least two autoantibodies and abnormal results of an oral glucose-tolerance test at trial entry,” wrote the authors who were led by Kevan C. Herold, M.D., Yale University. “Our findings support the notion that type 1 diabetes is a chronic T-cell–mediated disease and suggest that immunomodulation before the development of clinical disease can be useful.”

REFERENCE

Kevan C. Herold, M.D., Brian N. Bundy, Ph.D., et al. "An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes." NEJM. June 9, 2019. DOI: 10.1056/NEJMoa1902226