Safety and Efficacy of Teplizumab in T1D


Dr Kimberly Simmons reviews key findings from an initial study and extended follow-up on the safety and efficacy of teplizumab in delaying the progression of type 1 diabetes.

Robert Busch, MD: There were recent publications before the FDA granted approval. Dr Simmons, review the New England Journal of Medicine publication in terms of the outcome there and the extension published by Dr Emily Sims.

Kimberly Simmons, MD, MPH/MSPH: It’s my honor to share take-home messages from these papers because they’re landmark studies that have changed how we manage type 1 diabetes. The original paper from the TrialNet study, which has been mentioned before, is for individuals at risk of type 1 diabetes. Those patients were identified as being at risk by having multiple islet antibodies and some measure of dysglycemia. There were 72 patients, I believe, enrolled in this study. When you look at 2 years out from receiving the drug and the difference between the group that received teplizumab and the group that didn’t, you have 43% in the teplizumab arm who developed type 1 diabetes vs 72% in the control arm. That’s very statistically significant, looking at a 2-year delay being more common in individuals who received the drug compared with those who did not. Dr Sims and colleagues did a follow-up study looking at individuals to a median of 923 days. At that time the group that received the drug had almost a 3-year delay in diagnosis of diabetes compared with those who didn’t receive the drug.

The other important thing is that teplizumab isn’t going to work in everybody, but that shouldn’t be discouraging. When this follow-up study was done, 50% had developed diabetes, but that’s much less than the individuals who had received the placebo. In talking with rheumatology colleagues, that’s an amazing response rate, even in which individuals who’ve already developed rheumatology disease. If you’re looking at delaying the onset of a disease and have a rate that’s so much higher compared with placebo, it’s very exciting news.

Robert Busch, MD: What adverse effects were seen with the drug in the studies?

Kimberly Simmons, MD, MPH/MSPH: The adverse effects of teplizumab are relatively mild. The 1 that’s most common is related to the mechanism of action. The most common adverse effect is a decrease in white blood cell count: lymphopenia or neutropenia. That’s a transient decrease because with the mechanism of action, the cytotoxic T cells marginate into the periphery, the lymph nodes, and the GI [gastrointestinal] tract is what is thought from studies. When they come back, they have more of an exhaustive phenotype. You have this transient decrease in lymphocytes of up to about a month, but the important thing is that they come back into circulation and that there aren’t opportunistic infections that have been reported. There may be some increased upper-respiratory infections, but they’re all very mild. The other adverse effect that’s common during infusions is rashes—arithmetic, pruritic rashes. Classically they’re on the palms, butt, or the inner thighs, but they can be anywhere, all over the body, and typically respond well to antihistamines.

Robert Busch, MD: Do those come early on when you’re giving the drug? Is it something that would come earlier vs later, or is it at any time during the course?

Kimberly Simmons, MD, MPH/MSPH: In most patients we’ve seen, it’s after the first infusion. Sometimes it’s with the first infusion, but if they develop the rash, then it’s usually something that happens with each infusion. We’ll make sure they’re pretreated and then receive extra medication as needed.

Teresa Quattrin, MD: The rash varies because in some instances by the time I would leave a regular patient in an outpatient center and run over there, it would be fading already. We tell families, “If you see anything, take a picture.” We’re not talking a generalized, very severe and alarming rash in most cases, but premedication helps as well.

Transcript Edited for Clarity

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