Editorial
Copyright ©The Author(s) 2024.
World J Diabetes. Oct 15, 2024; 15(10): 2022-2035
Published online Oct 15, 2024. doi: 10.4239/wjd.v15.i10.2022
Table 1 Major studies evaluating the efficacy and safety of teplizumab
Ref.
Study design
Intervention
Population
Major outcome
Ramos et al[11], 2023PROTECT studyPhase 3, randomized, placebo-controlled trial with teplizumab or placebo for two 12-day coursesThe 328 participants, stage 3 T1D, age 8-17 years, within 6 weeks of diagnosisHigher stimulated c-peptide levels (teplizumab vs placebo) (least squares mean difference, 0.13 pmol per mL; 95%CI: 0.09-0.17; P < 0.001); no significant difference in HbA1c level, insulin requirement or hypoglycemia; ADR: headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome
Herold et al[12], 2019TrialNet studyPhase 2, randomized, placebo-controlled, double-blind trial of teplizumab (single 14-day course)The 76 participants, relatives of T1D, stage 2, age > 8 yearsLow-risk diagnosis of T1D (teplizumab vs placebo) (hazard ratio 0.41; 95%CI: 0.22-0.78; P = 0.006); longer median time to diagnose T1D (teplizumab vs placebo) (48.4 months vs 24.4 months); ADR of lymphopenia and rash
Herold et al[13], 2013AbATE StudyAn open-label, randomized, controlled trial with teplizumab (two of 14-day course, one year apart)The 83 participants, stage 3 T1D, age 8-30 years, within 8 weeks of diagnosisReduced decline in c-peptide at 2 years (-0.28 nmol/L; 95%CI: 0.36-0.20) vs control (-0.46 nmol/L; 95%CI: 0.57-0.35; P = 0.002); ADR: Rash, transient upper respiratory infections, headache, and nausea
Hagopian et al[14], 2013Protégé studyPhase 3, randomized, double-blind, parallel, placebo-controlled 2-years with teplizumab (3 dosing regimens, two of 14 days course, 26 weeks apart)The 462 of 516 participants completed 2 years follow up, stage 3 T1D, age 8-35 years, within 12 weeks of diagnosisReduced the loss of area under curve mean c-peptide at 2 years (teplizumab vs placebo) (P = 0.027); ADR: lymphopenia; no differences in adverse events or serious adverse events among groups at 2 years
Herold et al[15], 2013 Randomized placebo-controlled trialThe 63 participants, stage 3 T1D, within 4-12 months of diagnosisThe 21.7% higher c-peptide response (teplizumab vs placebo) [0.45 vs 0.371; difference, 0.059 nmol/L (95%CI: 0.006-0.115 nmol/L)] (P = 0.03); the teplizumab group required less exogenous insulin (P < 0.001) with no significant difference in HbA1c level; ADR: rash, lymphopenia and nausea
Table 2 Antigen-specific immunotherapies- strengths and weaknesses
Strategies
Immunological target
Advantages
Disadvantages
Autoantigenic peptides and proteinsAPCsBiocompatible; possibility to conjugate to a vehicleShort half-life; adjuvant required
Autoantigen-encoding plasmid DNAAPCsLong-lived effectGene therapy
Antigen-loaded cell-based strategiesAutoreactive T cellsPowerful immunoregulatory effectLeukapheresis required; personalized medicine
Antigen-loaded nanoparticles and liposomesAPCs and T cellsCustomizable; powerful immunoregulatory effect; might act by biomimicrySynthetic; preclinical developmental phase