medwireNews: Of the immunotherapies tested to date, teplizumab and low-dose antithymocyte globulin (ATG) are the most promising for slowing the decline in C-peptide in people with newly diagnosed type 1 diabetes, researchers report.
The team did a cross-trial comparison of three TrialNet studies and three from the Immune Tolerance Network, which Laura Jacobsen (University of Florida, Tampa, USA) presented at the 79th ADA Scientific Sessions in San Francisco, USA. To facilitate direct comparisons between the trials they normalized the data, by adjusting for age and baseline C-peptide levels.
These studies looked at abatacept, rituximab, low-dose ATG, teplizumab, alefacept, and high-dose ATG. The last two were included despite not meeting their primary endpoints, due to benefits on secondary endpoints or in specific subgroups.
Looking at the differences between the treated and placebo groups at 1 year, Jacobsen and team found that teplizumab (preferential T-effector cell depletion) and low-dose ATG (2.5 mg/kg; T-cell depletion, sparing T-regulatory cells) most strongly preserved C-peptide levels.
The team compared the preservation of C-peptide in these trials against the difference in rituximab trial, which Jacobsen said was “just an arbitrary choice, as one of the older trials”, and found that teplizumab preserved C-peptide by an additional 149% and low-dose ATG did so by an additional 142%.
High-dose ATG (6.5 mg/kg) was 47% less effective than rituximab and the other therapies were between 22% and 33% more effective.
At 2 years, teplizumab and low-dose ATG were again the most effective interventions, preserving C-peptide by a respective 303% and 216% more than did rituximab. The other treatments were between 13% and 141% more effective than rituximab.
“It’s interesting to remember that these people are getting their experimental therapy very early in these clinical trials,” said Jacobsen. “ATG was given over the first 2 days and then no other therapy was given – so 2 years later there’s still an effect over the placebo group.”
Participants in the teplizumab were retreated at 1 year, she noted, but again there was a significant effect over placebo at 2 years.
Jacobsen concluded: “Even more important than finding out which studies are successful is finding out – in those studies that are successful – which patients are actual clinical responders, so we can provide that directed therapy to those patients – a more of a personalized medicine approach.”
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ADA 2019; San Francisco, California, USA: 7–11 June
News story | Teplizumab delays onset of overt type 1 diabetes