An anti-CD3 antibody therapy significantly delayed onset of clinical diabetes in an at-risk population with diabetes autoantibodies.
Because type 1 diabetes mellitus (DM) is the result of immune destruction of pancreatic islet cells, immunologic interventions have shown promise in delaying its onset. In a phase II, international, randomized, placebo-controlled trial, researchers tested the efficacy of a 14-day regimen of intravenous teplizumab, an anti-CD3 antibody, for delaying the development of clinical DM in 76 at-risk participants. Most were children (ages 8–18; median age, 13–14 years) and white. All had a relative with DM, at least two DM-related autoantibodies, and recent abnormal glucose tolerance tests.
The median time to diagnosis of clinical DM was 48 months in the teplizumab group compared with 24 months in the placebo group (P=0.006). DM developed at an annual rate of 15% in the teplizumab cohort compared with 36% in the placebo group; the most profound between-group difference occurred in the first year — 7% vs. 44%, respectively. Having HLA-DR4 was associated with better response to teplizumab, as were absences of HLA-DR3 and antibodies to zinc transporter 8. Five times more adverse events were reported in the teplizumab group than in the placebo group (112 vs. 32); the most frequent adverse events among teplizumab recipients were transient lymphopenia (75%) and rash (36%).
Immune therapy can delay onset of clinical DM in those already in early stages of its natural history. While this is a significant advance, as editorialists state, it is not yet a cure. Yet these impressive results hold promise for the future.
Herold KC et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med 2019 Jun 9; [e-pub]. (https://doi.org/10.1056/NEJMoa1902226)
Rosen CJ and Ingelfinger JR. Traveling down the long road to type 1 diabetes mellitus prevention. N Engl J Med 2019 Jun 9; [e-pub]. (https://doi.org/10.1056/NEJMe1907458)
F. Bruder Stapleton, MD reviewing