TrialNet research reveals the benefits of Teplizumab in delaying clinical type 1 diabetes in people at high risk.
Siblings of people with type 1 diabetes are about 15-fold higher at risk of developing type 1 diabetes than the general population. This suggests that genetic factors play a role in the prevalence of this disease and is one of the indications that first degree relatives of people with type 1 diabetes could be at risk for developing diabetes.
Some studies have shown that some immune interventions have slowed the decline in beta-cell function in patients with new onset type 1 diabetes, caused by the autoimmune destruction of insulin-producing beta cells. Promising results of the new study “An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes” has been presented at the ADA’s 79th Scientific Sessions. The study objective was to test whether Teplizumab treatment can prevent or delay the onset of clinical type 1 diabetes in high-risk populations. The findings of this study are of great clinical relevance, especially for children.
This study was a phase 2 randomized, placebo controlled, double-blind trial of 76 participants, relatives of people with type 1 diabetes (more than half were siblings of people with type 1 diabetes), who did not yet have diabetes themselves but were at high risk of diabetes. Additional criteria for patients enrolling in the study were: >8yrs old at time of randomization, had 2 or more diabetes-related autoantibodies in 2 samples obtained within 6 months before randomization and evidence of dysglycemia during an oral glucose tolerance-test. The majority of the study population (57%) were children (<18 years). The participants were enrolled and randomly assigned to receive Teplizumab or placebo for 14 days. The primary endpoint of the study was the elapsed time from randomization to the clinical diagnosis of diabetes (criteria used from the ADA).
The median follow-up duration was 745 days and duration of follow-up was more than 3 years in 75% of the participants. 55% of the participants (n=42) were diagnosed with type 1 diabetes, with 19 out of 44 participants in the Teplizumab group (43%) with a median time of diagnosis of 48.4 months, and 23 out of 32 participants of the placebo group (72%) with a median time of diagnosis of 24.4 months. The results were found to be statistically significant with hazard ratio, 0.41; 95% [CI], 0.22 to 0.78; p=0.006.
40% (17 out of 42) of the participants that were diagnosed with type 1 diabetes, have progressed to type 1 diabetes in the first year after trial entry, and Teplizumab treatment had the largest effect on the first year, where only 7% of participants in the Teplizumab group were diagnosed versus 44% in the placebo group.
In terms of safety, some adverse effects were reported with Teplizumab therapy such as lymphopenia during the first 30 days of treatment, which seems to have resolved around day 45. A resolving rash has also occurred in 36% of participants in the Teplizumab group. In addition to that, 30% at trial entry had antibodies against Epstein-Barr virus and as Teplizumab is an anti-CD3 monoclonal antibody treatment, the risk of EBV reactivation is present, and has in fact occurred in 8 participants, all in the Teplizumab group, at weeks 3 through 6. However, the EBV DNA levels decreased to below levels of quantification between day 43 and 134. One participant in the Teplizumab group had detectable levels of CMV DNA at day 20 and undetectable by day 42, out of the 17 participants with CMV antibodies enrolled at trial entry.
At the end of the trial, 57% of participants in the Teplizumab group were diabetes free versus 28% in the placebo group.
In conclusion, treatment with Teplizumab significantly slowed down type 1 diabetes progression in participants that are nondiabetic relatives of people with type 1 diabetes, at high-risk of diabetes, with at least 2 diabetes related autoantibodies and dysglycemia.
- The findings of this study suggest that immunotherapy before the development of clinical type 1 diabetes could be really beneficial and is of great clinical relevance, especially for the younger population at high risk.
- A 14-day course of Teplizumab treatment has delayed the progression of type 1 diabetes in participants without diabetes but at high risk (relatives of people with type 1 diabetes, with at least 2 autoantibodies and an abnormal glucose-tolerance test result) as compared to placebo by a median of 2 years in children and adults.
- Expected adverse events of lymphopenia (levels returned to normal by day 45) and a resolving rash, have been reported in the Teplizumab group.
Steck AK, Rewers MJ. Genetics of type 1 diabetes. Clin Chem. 2011;57(2):176–185. doi:10.1373/clinchem.2010.148221
Herold KC, Bundy BN, Long SA, et al. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019 Jun 9. doi: 10.1056/NEJMoa1902226.
Marian Ayad, BSPharm, PharmD candidate, University of Colorado Skaggs School of Pharmacy
Reported at the American Diabetes Association 79th Scientific Sessions June, 2019