Teplizumab Therapy to Delay Onset and Progression of T1D

This transcript has been edited for clarity and length.

Javier Morales, MD: Let's ask the audience: how familiar are you with teplizumab? Kindly cast your votes now.

Personally, I’ve found it fascinating to learn about this medication over the years. As more data has become available, we’ve gained a better understanding of its potential utility in our patients. Let’s see what the audience says.

It seems most of you are at least somewhat familiar with teplizumab, and about half are very familiar with what it has to offer. Dr Choudhary, could you walk us through this agent and its FDA approval?

Abha Choudhary, MD: Absolutely. The approval of teplizumab was a significant milestone—it’s the first disease-modifying agent in endocrinology to receive FDA approval. This happened in November 2022.

Teplizumab, also known by its brand name Tzield, was approved to delay the progression of type 1 diabetes (T1D) from stage 2 to stage 3. It’s a monoclonal antibody targeting the CD3 molecule found on T cells. Essentially, it modulates the immune response, preserving beta-cell function by calming the immune system.

Mechanistically, it works by depleting T effector cells, exhausting their activity, and interfering with T-cell activation. In simple terms, it helps preserve beta-cell function, thereby preventing or delaying the progression to overt T1D.

The pivotal study, which led to FDA approval, was published in The New England Journal of Medicine. This multicenter, double-blind, randomized clinical trial included 76 participants. The study enrolled relatives of patients with T1D who were in stage 2, characterized by the presence of two or more autoantibodies and dysglycemia. Participants were randomized to receive either teplizumab or placebo for a 14-day outpatient course.

The primary outcome was the time from randomization to a clinical diagnosis of T1D. The results showed a significant delay in progression for the teplizumab group, with a median time to diagnosis of 48.4 months compared to 24.4 months in the placebo group—a delay of approximately 2 years.

When discussing side effects with my patients, I emphasize that teplizumab is not chemotherapy. It is a monoclonal antibody, and the side effects are generally minimal.

The most common side effect is lymphopenia, which is expected and can be profound. However, it typically peaks around days 4 or 5 of treatment and normalizes within weeks as treatment continues. This lymphopenia is due to transient migration of lymphocytes out of the bloodstream rather than systemic depletion.

Other reported side effects include rash, mild headaches, and neutropenia. Cytokine release syndrome (CRS) has been noted but occurs less frequently. CRS symptoms may include fever, body aches, and headaches. To mitigate this, we premedicate our patients with antihistamines, antipyretics, and antiemetics, along with adequate hydration, which has effectively reduced complications.

In some anecdotal cases, other centers have reported hypotension around days 4 or 5 of treatment, but this has been less common.

At our clinic, it took about 18 months to establish a workflow for teplizumab infusions. We now administer the 14-day course, including weekends, in our own clinic. Our prior experience as a site for the PROTECT study trial has given us confidence in treating children with this medication.

Overall, I reassure my patients that teplizumab is safe—it’s not chemotherapy, and they won’t lose their hair. While side effects are manageable, I’m interested to hear what the other panelists have observed in their practices.