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03-05-2021 | Teplizumab | News

Teplizumab offers extended preservation of beta-cell function

Eleanor McDermid

medwireNews: Prolonged follow-up of high-risk people treated with teplizumab to prevent progression to type 1 diabetes shows a lasting beneficial effect on beta-cell function, say researchers.

The participants of the phase 2 study were aged between 8 and 49 years, had relatives with type 1 diabetes, and already had at least two autoantibodies, but had not yet developed clinical diabetes. The researchers previously reported a median time to diagnosis of 48.4 months for those given teplizumab over a 14-day period on recruitment to the study, compared with 24.4 months in those given placebo.

This latest report is based on a median follow-up of 923 days, compared with 742 days in the original publication. By the end of the extended follow-up, the 44 teplizumab-treated participants remained significantly less likely to have developed diabetes, at 50% compared with 78% of the 32 placebo-treated participants.

Ten of the 13 people who were followed up for more than 60 months did not develop diabetes. Eight of these participants had received teplizumab and two were given placebo.

All study participants had a dysglycemic oral glucose tolerance test (OGTT) at the point of enrollment. During follow-up, they had progressively more diabetic OGTT results, but this progression was slower in people given teplizumab than those given placebo. Reflecting this, the average OGTT area under the curve, corrected for time in the study, remained significantly smaller in the teplizumab than the placebo group, at 165 versus 175 mg/dL.

Underlying this, teplizumab had a measurable effect on beta-cell function, report Kevan Herold (Yale University, New Haven, Connecticut, USA) and co-researchers in Science Translational Medicine.

Prior to randomization, stimulated C-peptide levels were declining in all participants, and this continued during the first 6 months of treatment for people in the placebo group, whereas levels significantly increased in the teplizumab group.

“Consistent with preclinical studies, the effects during this period of active disease support the concept that this intervention may be most effective when there is immune cell activation,” say the researchers.

When tested during the first 6 months, the teplizumab group had significant improvements in the total amount of insulin secreted during an OGTT, with the largest improvements seen during the early phase.

This indicates improvements in beta-cell function with teplizumab treatment, say Herold and team, rather than just better preservation of beta-cell mass.

After the first 6 months, C-peptide levels remained stable in the teplizumab group, but continued their slow decline in the placebo group. People in both groups experienced “a precipitous decline” in C-peptide levels during the 6 months before they were diagnosed with type 1 diabetes.

“The pronounced early efficacy of the drug followed by stabilization of beta cell function” implies that repeated doses of teplizumab, or the addition of complementary medications with different modes of action “may be valuable to extend the delay or prevent” the onset of type 1 diabetes, the team concludes.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

Sci Transl Med 2021; 13: eabc8980