Delaying the Onset of Type 1 Diabetes Through Early Intervention - Episode 9
Justin M. Gregory, MD, MSCI, provides an overview of the mechanism of action of teplizumab and its use in delaying T1D.
Steve Edelman, MD: Well, I think now is the time to talk about teplizumab. Justin, I’ve assigned you to tell us a little bit about the drug, how it works, and about the results in the clinical trial, and how to give it, but we’re all going to help with that.
Justin M. Gregory, MD, MSCI: Well, as you said, teplizumab is a monoclonal antibody that targets the CD3 receptor on T lymphocytes, and the CD3 receptor is a critical component of the T-cell receptor complex on the surface of T lymphocytes. By binding the CD3 receptor, teplizumab does something interesting, it modulates the activity of these T lymphocytes to where it induces an anergic state on these autoreactive T cell. So these T cells that are more prone to go after self-antigen are dampened down. What that does is it promotes immunological tolerance for the beta cells, and there’s some thought that teplizumab may also promote the regulatory functions of other T-cell subtypes, which also may be helpful. So it’s working on the T lymphocytes in a way that, bottom line, seems to promote cell tolerance.
A little less than a year ago, teplizumab was approved in stage II type 1 diabetes. I think we’re fortunate in that, like the [Indiana University] where Dr DiMeglio works, we have some experience with teplizumab and other immunological therapies because of our experience with teplizumab. We’ve tried to take that experience and have a committed clinic, we call it the Type 1 diabetes immunology clinic and we have started taking patients in the clinical setting now, not in the research setting, and started doing teplizumab infusions; that entails a 14-day infusion. Our practice is that, and we’re having children and adults, we like to put in PICC lines, there are these IVs that last for up to 2 weeks so that you’re not having to do multiple IV placements. We do that at first, and then for 14 days you’re given a teplizumab infusion. Now the teplizumab infusion itself lasts about 30 minutes, and then we observe our patients for about an hour after that. On the first day, you get a fairly small dose, and over the course of the first 5 days of the 14, you start ramping that up. That’s based off of studies like TN10 that showed that if you start out at a smaller dose, the side effects are significantly less. You might see some of the adverse effects. The rash seems like the biggest one that we encounter, but it’s not usually severe. Once you’re at day 5, things generally tend to go swimmingly after that. The only other thing I’ll add to that is often what’s been found to be helpful is to pretreat patients before you give teplizumab.We will pretreat with acetaminophen, diphenhydramine, and often, at least in the first few days, we’ll do ondansetron, Zofran, and that seems to help out quite a bit.
Steve Edelman, MD: Anything to add, Linda?
Linda A. DiMeglio, MD: No. I think that that was a great description of it. We have college, just an early-stage diabetes clinic, but we have a space at Indiana University. We haven’t actually given our first infusion yet, but we have the setup. The other thing is that most centers, I think because of what Justin described so nicely, are opting to do that first course, either as an inpatient or more commonly in an outpatient infusion center, but then after that, a lot of places are transitioning to home health for the additional days, depending on what the setup is at a given institution. But yeah, by day 5 you know what’s going on with that patient.
Steve Edelman, MD: There’s support services that are out there, that if you have a patient that fits the criteria, which is 8 or older, 2 positive autoantibodies, dysglycemia, you can find out where there’s a local infusion center. You don’t have to do any of that yourself. Being at a university, I know Schafer’s involved with setting up, it makes it a lot easier. There are certain laboratory data that you follow CBC [complete blood count], liver function.
Transcript edited for clarity