Teplizumab is a novel therapeutic agent representing a significant advancement in type 1 diabetes management. It is the first approved pharmacotherapy specifically designed to delay the onset of clinical type 1 diabetes. This innovative treatment offers a new approach for individuals at risk, addressing the progression of this chronic autoimmune condition.
Understanding Type 1 Diabetes and Its Progression
Type 1 diabetes is an autoimmune disease where the body’s immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. These specialized cells create insulin, a hormone necessary for converting blood sugar into energy. Without adequate insulin, blood sugar levels remain elevated, leading to complications.
The progression of type 1 diabetes unfolds through distinct stages before a clinical diagnosis. Stage 1 involves two or more diabetes-related autoantibodies in the blood, indicating an immune system attack on beta cells, even with normal blood sugar and no symptoms.
In Stage 2, individuals still exhibit two or more autoantibodies, but their blood sugar levels become abnormal, a condition known as dysglycemia, without overt symptoms. This stage signifies a more advanced loss of beta cell function.
Stage 3 is characterized by the onset of symptomatic disease, typically when a clinical diagnosis occurs. At this point, substantial beta cell loss leads to noticeable symptoms such as increased thirst, frequent urination, and unexplained weight loss. Identifying individuals in earlier stages, particularly Stage 2, is helpful for interventions like teplizumab.
How Teplizumab Intervenes
Teplizumab functions as an anti-CD3 monoclonal antibody, specifically targeting CD3, a protein complex found on the surface of T cells. T cells are immune cells that play a direct role in the autoimmune destruction of pancreatic beta cells in type 1 diabetes. By binding to CD3, teplizumab modulates the activity of these T cells.
The drug aims to reset the immune system by inducing a state of immune tolerance. This involves a transient activation of T cells, which then leads to their inactivation or anergy. Teplizumab also promotes an increase in regulatory T cells, which help control the immune response and maintain tolerance to the body’s own tissues.
Teplizumab reduces pro-inflammatory cytokines, signaling molecules that contribute to inflammation and tissue damage. It also influences the movement of T cells, limiting their infiltration into the pancreatic islets where beta cells reside. Through these combined actions, teplizumab works to preserve remaining beta cell function by reducing the immune system’s attack.
Who Can Benefit from Teplizumab?
Teplizumab is indicated for individuals at risk of developing clinical type 1 diabetes, specifically those diagnosed with Stage 2. Eligible individuals must have laboratory evidence of two or more diabetes-related autoantibodies, such as glutamic acid decarboxylase 65 (GAD65) autoantibody, insulin autoantibody (IAA), or zinc transporter 8 autoantibody (ZnT8A). The presence of these autoantibodies indicates ongoing autoimmune activity.
In addition to autoantibodies, candidates for teplizumab must also exhibit dysglycemia without overt hyperglycemia. This is confirmed through an oral glucose tolerance test (OGTT), showing abnormal blood sugar levels. The individual must not yet be symptomatic of type 1 diabetes, nor should their clinical history suggest type 2 diabetes.
The current approval for teplizumab is for adults and pediatric patients aged 8 years and older who meet these Stage 2 criteria.
Screening for at-risk individuals is conducted in people with first-degree relatives who have type 1 diabetes, though most newly diagnosed individuals do not have a positive family history. Identifying these individuals before symptomatic onset allows teplizumab to intervene in the disease progression.
Outcomes and Practical Considerations
Teplizumab’s primary outcome is its ability to delay the onset of Stage 3, or clinical, type 1 diabetes. Clinical trials have shown that a single 14-day course of teplizumab delayed the median time to diagnosis of Stage 3 type 1 diabetes. In one study, the median time to diagnosis was 50 months for those who received teplizumab, compared to 25 months for those who received placebo.
Teplizumab provides a delay, rather than a cure, for type 1 diabetes. The drug is administered intravenously (IV infusion) once daily for 14 consecutive days. This course of treatment is designed to modulate the immune system for a sustained period.
Common side effects include transient lymphopenia (a temporary decrease in a type of white blood cell), rash, leukopenia (a general decrease in white blood cells), and headache. Cytokine release syndrome and hypersensitivity reactions are also possible, typically occurring early in the treatment course. Teplizumab, marketed as Tzield, received approval from the U.S. Food and Drug Administration (FDA) in November 2022.