The study findings shed light on the viability of Teplizumab as prophylaxis for type 1 diabetes in direct relatives of current patients.
Type 1 Diabetes Mellitus, an autoimmune disease that is typically found in children and adolescents, is the most common chronic childhood disease. Type 1 diabetes causes the destruction of the beta cells, located in the islets of Langerhans of the pancreas. These beta cells are tasked with producing insulin for the use of energy in the body. Insulin is the “bus” that transports glucose to the surrounding cells of the body. In patients who have type 1 diabetes, there is no insulin to transport the glucose to the cells, leaving the body without energy and the glucose in the blood. This could induce a hypoglycemic episode, which can, potentially, result in death. Type 1 and type 2 diabetes differ in their basic etiology and presentation. Type 2 diabetes is normally caused by the body’s desensitization of insulin that is produced by the body, while Type 1 diabetes is the total absence of insulin production due to the destruction of the beta cells in the pancreas.
Because patients who have type 1 diabetes are genetically susceptible, it is becoming exceedingly important to screen relatives of those who have type 1 diabetes and to develop a method of prevention. This article notes various immunological interventions previously studied, which could potentially delay the clinical onset of type 1 diabetes. One such therapy is the Fc receptor-non-binding anti-CD3 monoclonal antibody medication, Teplizumab. Through multiple studies, it was shown to delay the destruction of beta-cell function. This drug works by modifying the CD8 T cell function, which is thought to be the cells that destroy the pancreatic beta cells. The researchers of this article set out to see whether they would be able to prevent or delay the onset of type 1 diabetes with the treatment of Teplizumab in patients who are at a high risk of developing the disease.
In this randomized phase 2 trial, candidates who were eligible to participate had to meet the following criteria: patients must not have diabetes and must be relatives of patients with type 1 diabetes, and be of at least eight years of age at the time of randomization. They must also be at a high risk of developing type 1 diabetes. Patients were also required to have two or more diabetes-related auto-antibodies detected in two separate samples obtained within six months. Also, patients were required to have evidence of dysglycemia during the Glucose Tolerance Test (defined as having a postprandial blood glucose level of at least 140mg/dL). Patients were randomly assigned to one of two groups on a 1:1 ratio basis. The first group was to receive the Teplizumab intervention while the second group was the placebo-controlled group. The primary endpoint was the elapsed time from randomization to the clinical diagnosis of diabetes, using the diagnosis criteria endorsed by the American Diabetes Association. For the 112 potential participants, 76 underwent randomization, placing 44 in the Teplizumab intervention group while 32 were placed in the placebo-controlled group.
The statistical analysis of this phase 2 trial yielded the following; 19 of the 44 (43%) participants in the Teplizumab group were diagnosed with type 1 diabetes, compared to 23 of the 32 (72%) participants in the placebo-controlled group. Where the data begins to show even more significance is when the mean time to diagnosis is the measure. In the intervention group, the mean diagnosis time was measured to be 48.4 months, while the placebo group’s mean diagnosis time was measured at 24.4 months (hazard ratio, 0.41; 95% confidence interval [CI], 0.22 to 0.78; P=0.006). The addition of Teplizumab therapy to high-risk patients without diabetes shows a significant delay in diagnosis time, when comparing it to that of the placebo group, delaying the time to diagnosis by almost double.
Although the results of this study were quite promising and proved the hypothesis that was set forth, it is important to note that there are variables that must be accounted for, and further analyzed, before it is marketed to the general population as a prophylaxis therapy of type 1 diabetes. Certain genetic variations of the MHC allele, HLA-DR3, HLA-DR4, and ZnT8 antibodies have been shown to alter the efficacy of Teplizumab therapy. Because of the size of the trial, it is important that the researchers continue to look for other alleles, antibodies, and genes that can potentially change the efficacy of the drug, as they progress into the later phases of this trial.
- The use of Teplizumab in relatives of patients with type 1 diabetes proved to be effective in delaying time to diagnosis.
- The efficacy of Teplizumab is dependent on genetic factors, alleles, and antibodies. Providers should test for various genetic variations before the initiation of this medication.
- Teplizumab has various side effects related to the monoclonal antibody drug class. It is important to educate the patient on the potential risks and benefits before initiation.
Reference for “Teplizumab as Prophylaxis Therapy”:
Herold, K. C., Bundy, B. N., Long, S. A., Bluestone, J. A., Dimeglio, L. A., Dufort, M. J., . . . Greenbaum, C. J. (June 09, 2019). An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. New England Journal of Medicine. doi:10.1056/nejmoa1902226
Usif Darwish, PharmD Candidate, Florida A&M University, College of Pharmacy & Pharmaceutical Sciences