Immunotherapy in type 1 diabetes: Novel pathway to the future ahead

Table 1 Major studies evaluating the efficacy and safety of teplizumab

Ref.	Study design	Intervention	Population	Major outcome
Ramos et al[11], 2023	PROTECT study	Phase 3, randomized, placebo-controlled trial with teplizumab or placebo for two 12-day courses	The 328 participants, stage 3 T1D, age 8-17 years, within 6 weeks of diagnosis	Higher 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], 2019	TrialNet study	Phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (single 14-day course)	The 76 participants, relatives of T1D, stage 2, age > 8 years	Low-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], 2013	AbATE Study	An 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 diagnosis	Reduced 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], 2013	Protégé study	Phase 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 diagnosis	Reduced 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 trial	The 63 participants, stage 3 T1D, within 4-12 months of diagnosis	The 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

ADR: Adverse drug reaction; CI: Confidence interval; HbA1c: Glycosylated hemoglobin; T1D: Type 1 diabetes.