ESPE Yearbook of Paediatric Endocrinology

Brief summary: This commentary discusses the implications of the recent licensing of Teplizumab by the Food and Drug Administration (FDA) as the first immunosuppressant for individuals at risk for type 1 diabetes (T1D).

The approval of Teplizumab by the FDA in November 2022, as an intervention to delay the onset of stage 3 T1D (clinical T1D) in adults and children aged 8 or older who have stage 2 T1D (two or more islets autoantibodies and dysglycemia but no symptoms), marks a milestone and new era for the management of T1D. Remarkably, this approval happened just a century after the discovery of insulin.

Teplizumab (brand name Tzield) is a humanised anti-CD3 monoclonal antibody, which was approved based on data from a randomized clinical trial, where 77 first-degree relatives of T1D patients received either teplizumab or placebo, in the form of a single 14-day course of intravenous infusions, to delay progression from stage 2 to stage 3 T1D (2). 45% of people who received teplizumab were later diagnosed with stage 3 T1D compared with 72% of those on placebo. Treatment with teplizumab delayed by 24-32 months the onset of clinical T1D and therefore the need for insulin therapy.

Although the approval of teplizumab is undoubtedly a milestone in T1D, it comes with issues and barriers to overcome. Firstly, teplizumab is an immunosuppressive agent associated with side effects during the treatment phase, including, among others, transient lymphopenia, cytokine release syndrome, risk of infections and hypersensitivity reactions. In addition, Teplizumab treatment consists in a 14-day infusion, and the estimated price is around $200 000. With the availability of a ‘prevention agent’, the focus is now on the need for screening programs to identify people at risk who could receive treatments to modify the early disease course during the asymptomatic phase that precedes symptom onset (1). Population screening for T1D was already reviewed in Yearbook 2022 (3), and has gained even further interest in the last year, with several screening programs being tested in different countries, as well as the planning of pre-T1D registries, and the development of consensus guidelines on screening and subsequent monitoring of individuals identified with autoantibodies (4).

References: 1. Hirsch JS. FDA approves teplizumab: a milestone in type 1 diabetes. Lancet Diabetes Endocrinol 2023;11(1):18. 2. Herold KC, Bundy BN, Long SA, et al. An Anti-CD3 antibody, Teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 2019;381(7):603–613. 3. Sims EK, Besser REJ, Dayan C, et al. Screening for type 1 diabetes in the general population: A status report and perspective. Diabetes. 2022;71(4):610–623. 4. Besser REJ, Bell KJ, Couper JJ, et al. ISPAD Clinical Practice Consensus Guidelines 2022: Stages of type 1 diabetes in children and adolescents. Pediatr Diabetes. 2022;23(8):1175–1187.