What is the recommended use and administration of Teplizumab (anti-CD3 monoclonal antibody) for autoimmune conditions?

Teplizumab for Delaying Type 1 Diabetes Onset

Teplizumab-mzwv should be offered to individuals aged ≥8 years with Stage 2 type 1 diabetes (multiple islet autoantibodies plus dysglycemia without symptoms) to delay progression to Stage 3 symptomatic disease, administered as a 14-day intravenous infusion course in a setting with appropriately trained personnel. 1

Approved Indication and Patient Selection

• Teplizumab is FDA-approved specifically for delaying the onset of Stage 3 type 1 diabetes in patients aged 8 years and older with Stage 2 type 1 diabetes 2
• Stage 2 type 1 diabetes is defined by the presence of multiple islet autoantibodies (≥2 autoantibodies including IAA, GADA, IA-2A, or ZnT8A) plus dysglycemia without clinical symptoms 1
• The drug is not indicated for other autoimmune conditions—its approval is limited exclusively to type 1 diabetes prevention 2

Clinical Efficacy Data

• In the pivotal trial, teplizumab delayed median time to Stage 3 diagnosis from 24.4 months (placebo) to 48.4 months (teplizumab), representing a doubling of disease-free time 1
• Stage 3 diabetes developed in 43% of teplizumab-treated patients versus 72% of placebo patients (HR 0.41,95% CI 0.22-0.78) 1
• Predictors of superior response include presence of HLA-DR4 (HR 0.20), absence of HLA-DR3 (HR 0.18), and absence of anti-zinc transporter 8 antibody (HR 0.07) 1

Administration Protocol

• Dosing regimen: 14 consecutive daily intravenous infusions with escalating doses based on body surface area 2
• Treatment must occur in a facility with personnel trained in managing infusion reactions and immune-mediated adverse events 1
• The drug binds to CD3 on T lymphocytes, causing internalization of the CD3 complex and modulating autoreactive T cells through partial agonistic signaling 2

Safety Profile and Monitoring Requirements

• Most common adverse reaction: Transient lymphopenia occurs in 73% of patients, with nadir on day 5 of the 14-day course 1, 2
• Second most common: Rash develops in 36% of patients 1
• Lymphopenia resolves without T-cell depletion, as the mechanism involves CD3 internalization rather than cell destruction 2
• Anti-teplizumab antibodies develop in approximately 57% of treated patients, with 46% developing neutralizing antibodies 2

Critical Contraindications and Precautions

• Pregnancy: Teplizumab should not be used during pregnancy unless clinical benefit clearly outweighs risk, as IgG antibodies cross the placental barrier 2
• Lactation: Women should interrupt breastfeeding and pump-and-discard for 20 days after administration to minimize infant exposure 2
• Age restriction: Safety and effectiveness have not been established in children younger than 8 years 2
• The drug has not been evaluated in patients with severe renal impairment (creatinine clearance <30 mL/min) or moderate-to-severe hepatic impairment 2

Mechanism of Action and Long-Term Effects

• Teplizumab is a CD3-directed humanized monoclonal antibody engineered with decreased Fc receptor binding to reduce cytokine release syndrome 1, 2
• The mechanism involves deactivation of pancreatic beta cell autoreactive T lymphocytes, with increases in regulatory T cells and exhausted CD8+ T cells 2
• This represents the first disease-modifying therapy for any autoimmune disease that delays clinical onset without requiring continuous administration 3, 4

Practical Implementation Considerations

• Patients require screening for multiple islet autoantibodies (IAA, GADA, IA-2A, ZnT8A) to identify Stage 2 disease 1, 4
• Oral glucose tolerance testing is necessary to confirm dysglycemia in autoantibody-positive individuals before treatment eligibility 1
• The 14-day treatment course does not require repeat dosing, distinguishing it from chronic immunosuppressive therapies 2, 3
• Terminal elimination half-life is 4.5 days with clearance of 2.7 L/day in a 60 kg patient 2

Evidence Quality and Clinical Context

• The approval is based primarily on a single randomized trial (Study TN-10) in relatives of people with type 1 diabetes, representing the highest quality evidence available 1
• The American Diabetes Association's 2025 Standards of Care provide the most recent guideline recommendation (Recommendation 3.15) 1
• Teplizumab achieves efficacy without global immune suppression, a critical advantage over traditional immunosuppressive approaches 3
• The drug represents over 30 years of development, evolving from transplant immunology research to become the first approved preventive treatment for type 1 diabetes 3, 5