Teplizumab: promises and challenges of a recently approved monoclonal antibody for the prevention of type 1 diabetes or preservation of residual beta cell function

ABSTRACT

Introduction

Type 1 diabetes (T1D) is a chronic autoimmune endocrinopathy with increasing incidence that results in the depletion of pancreatic beta cells and exogenous insulin dependence. Despite technological advances in insulin delivery, disease control remains suboptimal, while previous immunotherapy options have failed to prevent T1D. Recently, teplizumab, an immunomodulating monoclonal antibody, was approved to delay or prevent T1D.

Areas covered

Five randomized controlled trials have tested different regimens of administration, mostly 14-day schemes with dose escalation. In participants with new-onset T1D, teplizumab delayed C-peptide decline, improved glycemic control, and reduced insulin demand for a median of 1 or 2 years. Studies in at-risk relatives of patients showed a decrease in T1D incidence during 2 years of follow-up. Subgroups of responders with unique metabolic and immunological characteristics were identified. Mild to moderate adverse effects were reported, including transient rash, cytopenia, nausea, vomiting, and infections.

Expert opinion

Teplizumab marks a turning point in T1D therapy. Areas of future research include the ideal population for screening, cost-effectiveness, and challenges in treatment accessibility. More studies are essential to evaluate the ideal duration of the regimen, the potential benefit of combinations with other drugs, and to identify endophenotypes with a high probability of response.

KEYWORDS:

• Type 1 diabetes
• teplizumab
• immunotherapy
• immunomodulation
• monoclonal antibody

Article highlights

• Teplizumab is the first pharmacological agent approved to prevent or delay type 1 diabetes.

• In new-onset stage 3 disease, teplizumab reduced C-peptide decline and insulin requirements.

• Mild to moderate adverse effects were reported with various dosing schemes.

• The positive response predictors included younger age, higher baseline C-peptide in stage 3 type 1 diabetes, lower baseline C-peptide in relatives at-risk, higher insulin sensitivity, markers of T cell exhaustion, absence of antiZnT8 antibodies, increased CD8+ T cytotoxic lymphocyte populations, HLA-DR4 positive and HLA-DR3 negative haplotypes.

• Combination therapies with other pharmacologic agents, immunomodulating or not, are yet to be investigated to augment the efficacy and safety of teplizumab.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contributions

G Tsatsani and NM Fanaropoilou reviewed the literature and drafted the manuscript. T Koufakis and K Kotsa reviewed the literature and edited the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

Additional information

Funding

This paper was not funded.