Teplizumab for Prevention of Type 1 Diabetes in High-Risk Individuals
Teplizumab-mzwv infusion should be administered to individuals aged ≥8 years with stage 2 type 1 diabetes to delay the onset of symptomatic (stage 3) type 1 diabetes. 1
Definition and Identification of High-Risk Individuals
Stage 2 type 1 diabetes is defined as having:
- Two or more pancreatic islet autoantibodies (GAD65, IAA, IA-2A, ZnT8A, or ICA) 2
- Dysglycemia on oral glucose tolerance testing 2
- No clinical symptoms of diabetes yet 1
Evidence Supporting Teplizumab Use
- FDA approval was based on a randomized controlled trial of relatives of people with type 1 diabetes 1
- In this pivotal study:
- Median time to stage 3 type 1 diabetes diagnosis was 48.4 months in the teplizumab group vs. 24.4 months in the placebo group (delay of approximately 2 years) 1, 2
- Type 1 diabetes was diagnosed in 43% of participants who received teplizumab vs. 72% who received placebo (HR 0.41; 95% CI 0.22-0.78) 1, 3
- The annualized rates of diabetes diagnosis were 14.9% per year with teplizumab vs. 35.9% per year with placebo 3
Predictors of Response to Teplizumab
Certain genetic and immunologic factors predict better response to teplizumab:
- Presence of HLA-DR4 (HR 0.20; 95% CI 0.09-0.45) 1
- Absence of HLA-DR3 (HR 0.18; 95% CI 0.07-0.45) 1
- Absence of anti-zinc transporter 8 antibody (HR 0.07; 95% CI 0.02-0.26) 1, 3
Administration Protocol
- Teplizumab is administered as a 14-day course of intravenous infusions 1, 2
- Treatment should be administered in a setting with appropriately trained personnel due to potential adverse effects 1
- The medication binds to CD3 on T lymphocytes, with a mechanism that may involve partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes 2
Common Adverse Effects
- Transient lymphopenia (73% of patients) - nadir typically occurs on day 5 of treatment 2
- Rash (36% of patients) 1, 2
- Cytokine release syndrome - may include fever, fatigue, muscle/joint pain, nausea, headache 2
- Higher incidence of rash in patients who develop anti-teplizumab antibodies 2
Important Considerations and Precautions
- Approximately 57% of treated patients develop anti-teplizumab antibodies, 46% of whom develop neutralizing antibodies 2
- Patients should receive all age-appropriate vaccinations prior to starting teplizumab 2
- Avoid concurrent use of live, inactivated, and mRNA vaccines with teplizumab 2
- For lactating women, breastfeeding should be interrupted during treatment and for 20 days after teplizumab administration 2
Ongoing Research
- Teplizumab has also shown benefit in preserving β-cell function in newly diagnosed type 1 diabetes (stage 3), though with less impact on clinical endpoints like insulin requirements 4
- Additional studies are investigating optimal treatment regimens, potential combinations with other therapies, and identification of patients most likely to respond 5
- Other immunomodulatory approaches are being studied for both prevention and treatment of type 1 diabetes 6, 7
Limitations and Challenges
- Long-term effects beyond the study period (median follow-up of 51 months) are not yet fully established 2
- Treatment requires a specialized setting with trained personnel to monitor and manage potential adverse effects 1
- Screening programs to identify appropriate candidates for treatment are still being developed 1