Two-Year Follow-up From the T1GER Study: Continued Off-Therapy Metabolic Improvements in Children and Young Adults With New-Onset T1D Treated With Golimumab and Characterization of Responders

Abstract

Objective: The T1GER (A Study of SIMPONI to Arrest β-Cell Loss in Type 1 Diabetes) study showed many metabolic benefits of the tumor necrosis factor-α blocker golimumab in children and young adults with type 1 diabetes (T1D). Off-therapy effects are reported.

Research designs and methods: T1GER was a phase 2, placebo-controlled, randomized trial in which golimumab or placebo was administered for 52 weeks to participants 6-21 years old diagnosed with T1D within 100 days of randomization. Assessments occurred during the 52-week on-therapy and 52-week off-therapy periods.

Results: After treatment was stopped, C-peptide area under the curve (AUC) remained greater in the treatment versus control group. At weeks 78 and 104, the golimumab group had lower reductions in the 4-h C-peptide AUC baseline than the placebo group, where specifically the golimumab group had reductions of 0.31 and 0.41 nmol/L, and the placebo group had reductions of 0.64 and 0.74 nmol/L. There were also trends in less insulin use, higher peak C-peptide levels and those in partial remission, and higher peak C-peptide levels in the golimumab group. Golimumab responders, defined as having an increase or minimal loss of C-peptide AUC and/or being in partial remission at week 52, showed even greater improvements in most metabolic parameters on and off therapy and had less hypoglycemia during the off-therapy period versus placebo. Adverse events, including infections, were similar between the groups during all time periods of the study.

Conclusions: In children and young adults with new-onset T1D, golimumab preserved endogenous β-cell function and resulted in other favorable metabolic parameters on and off therapy. A subpopulation had disease stabilization while on therapy, with improved metabolic parameters off therapy.

Graphical abstract

Figure 1

Change in the 4-h C-peptide AUC over time and lag time of C-peptide decline in those treated with golimumab or placebo over 52 weeks on therapy and observed for an additional 52 weeks off therapy. A: Mean change in AUC of the 4-h C-peptide from baseline over time by treatment group. B: Comparative rate of fall (slope) in the C-peptide AUC by treatment group as a whole.

Figure 2

Additional metabolic analyses in the in golimumab group as a whole vs. the placebo group from baseline to week 104. HbA_1c (A), exogenous insulin use (B), peak C-peptide levels (C), and IDAA1C score (D). E: Percentage of participants with C-peptide ≥0.2 nmol/L. F: Percentage of participants in T1D partial remission, defined as an IDAA1c score of ≤9.

Figure 3

Hypoglycemia in the whole (A) and subpopulation (B) treatment groups. 1: Annualized event rates (events per patient-year) of BG levels <70 mg/dL during the on-therapy period (week 0–52), off-therapy period (week 52–104), and the entirety of the study (week 0–104). 2: Annualized event rates (events per patient-year) of BG levels <70 mg/dL but ≤54 mg/dL during the on-therapy period (week 0–52), off-therapy period (week 52–104), and the entirety of the study (week 0–104). 3: Annualized event rates (events per patient-years) of BG levels <54 mg/dL during the on-therapy period (weeks 0–52), off-therapy period (weeks 52–104), and the entirety of the study (week 0–104). GOL, golimumab group (as a whole); GOL-NR, golimumab nonresponder subgroup; GOL-R, golimumab responder subgroup; PBO, placebo group.

Figure 4

Percentages of responders by treatment group. Percentages of participants in the golimumab or placebo groups who had C-peptide levels ≥5% loss from baseline at week 52 (C-peptide), an IDAA1C score of ≤9 at week 52 (partial remission), either or both at week 52. GOL, golimumab group; PBO, placebo group.

Figure 5

Metabolic analyses in the in golimumab subgroups vs. the placebo group from baseline to week 104. A: Mean change in AUC of 4-h C-peptide from baseline over time. HbA_1c (B), exogenous insulin use (C), peak C-peptide levels (D), and IDAA1C score (E). F: Percentage of participants with C-peptide ≥0.2 nmol/L. G: Percentage of participants in T1D partial remission, defined as an IDAA1C score of ≤9.