Rheuma drug shows disease-modifying potential for T1D

Findings from the phase IIa T1GER study revealed the therapeutic potential of the monoclonal antibody golimumab for children and young adults with type 1 diabetes (T1D).

“There are no approved disease-modifying therapies for T1D,” said Dr Teresa Quattrin from the Jacobs School of Medicine and Biomedical Sciences, University of Buffalo in New York, US, during her presentation of the initial results. “[As such,] there is a significant need for therapies that slow the progression of T1D autoimmunity and disease,” noted Dr Eric Felner from the Emory University School of Medicine in Atlanta, Georgia, US, in his poster presentation of the subgroup findings.

Golimumab specifically targets TNFα*, a pro-inflammatory cytokine influencing T1D initiation and progression, and is approved for the treatment of rheumatic diseases**.

The team sought to determine the role of golimumab in T1D. Eighty-four participants (mean age 14 years, 60 percent male) were randomized 2:1 to receive SC golimumab*** or placebo for 52 weeks. [EASD 2020, abstract 53]

At week 52, C-peptide area under the curve (AUC) after a 4h MMTT^# was higher with golimumab vs placebo (mean, 0.64 vs 0.43 pmol/mL; p<0.001). “[The] C-peptide change … started at week 12 and persisted throughout the study,” said Quattrin.

C-peptide is a widely used measure of pancreatic β cell function, with low levels suggesting diabetes-related complications. [Diabetes Ther 2017;8:475-487; Diabetes Med 2015;32:1346-1353] Therefore, this finding underscores the potential of golimumab to preserve β cell function and prevent possible complications in individuals with T1D.

Although HbA_1c was numerically lower with golimumab vs placebo, the difference was not significant (p=0.80). “As often observed in clinical trials, an initial decline in HBA_1c was observed in both groups over the first 4 weeks. But over time, HbA_1c appeared to be lower with golimumab vs placebo,” noted Quattrin.

Increase in daily insulin use was lower with golimumab vs placebo (0.07 vs 0.24 U/kg; p=0.001), as was the absolute amount of insulin used (0.51 vs 0.69 U/kg).

Also, more golimumab vs placebo recipients were using a daily insulin dose of <0.5 U/kg (n=21 vs 3) and ≤0.25 U/kg (n=7 vs 0). “[These suggest] that golimumab provides optimal glycaemic control with low insulin dose,” said Quattrin.

There were also more golimumab vs placebo recipients who had C-peptide increase or minimal loss (41 percent vs 11 percent), who were in partial remission (IDAA_1c^## remission score <9; 43 percent vs 7 percent), or both (29 percent vs 4 percent). “These suggest that golimumab may be arresting disease progression for a large subset of patients,” noted Quattrin.

The rates of serious adverse events (AEs; 2 percent vs 4 percent) and drug-related AEs (43 percent in each arm) were similar between the golimumab and the placebo arms. Treatment discontinuation rate owing to AEs was higher with golimumab vs placebo (4 percent vs 0 percent), as was the incidence of hypoglycaemia reported at investigator’s discretion (23 percent vs 7 percent).

In a subgroup of participants aged 6–17 years (n=68), golimumab use led to a significantly less change in C-peptide AUC (mean, 0.11 vs 0.55 pmol/mL; p_nominal<0.0001), less increase in insulin use (0.06 vs 0.27 U/kg/day; p_nominal=0.0004), lower absolute insulin use (0.53 vs 0.74 U/kg/day), and numerically lower hypoglycaemic event rates (42 percent vs 48 percent) vs placebo. [EASD 2020, abstract 631]

“[Taken together, the findings] demonstrate the ability [of golimumab] to preserve endogenous insulin production, reduce exogenous insulin requirements, and improve clinical and metabolic parameters in children and young adults with newly diagnosed stage 3 T1D … These results support golimumab as a potential disease-modifying therapy for T1D,” said Quattrin. Further evaluation is warranted to validate the findings.