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Multicenter Study
. 2021 Oct;37(7):e3440.
doi: 10.1002/dmrr.3440. Epub 2021 Feb 18.

Combined Etanercept, GAD-alum and vitamin D treatment: an open pilot trial to preserve beta cell function in recent onset type 1 diabetes

Johnny Ludvigsson  1 , Indusmita Routray  2 , Tore Vigård  3   4 , Ragnar Hanås  5   6 , Björn Rathsman  7 , Annelie Carlsson  8   9 , Stefan Särnblad  10 , Anna-Karin Albin  11 , Carl-Göran Arvidsson  12 , Ulf Samuelsson  1 , Rosaura Casas  2
Affiliations
Multicenter Study

Combined Etanercept, GAD-alum and vitamin D treatment: an open pilot trial to preserve beta cell function in recent onset type 1 diabetes

Johnny Ludvigsson et al. Diabetes Metab Res Rev. 2021 Oct.

Abstract

Aim: We aimed to study the feasibility and tolerability of a combination therapy consisting of glutamic acid decarboxylase (GAD-alum), Etanercept and vitamin D in children and adolescents with newly diagnosed with type 1 diabetes (T1D), and evaluate preservation of beta cell function.

Material and methods: Etanercept Diamyd Combination Regimen is an open-labelled multi-centre study pilot trial which enrolled 20 GAD antibodies positive T1D patients (7 girls and 13 boys), aged (mean ±SD): 12.4 ± 2.3 (8.3-16.1) years, with a diabetes duration of 81.4 ± 22.1 days. Baseline fasting C-peptide was 0.24 ± 0.1 (0.10-0.35) nmol/l. The patients received Day 1-450 Vitamin D (Calciferol) 2000 U/d per os, Etanercept sc Day 1-90 0.8 mg/kg once a week and GAD-alum sc injections (20 μg, Diamyd™) Day 30 and 60. They were followed for 30 months.

Results: No treatment related serious adverse events were observed. After 6 months 90-min stimulated C-peptide had improved in 8/20 patients and C-peptide area under the curve (AUC) after Mixed Meal Tolerance Test in 5 patients, but declined thereafter, while HbA1c and insulin requirement remained close to baseline. Administration of Etanercept did not reduce tumour necrosis factor (TNF) spontaneous secretion from peripheral blood mononuclear cells, but rather GAD65-induced TNF-α increased. Spontaneous interleukin-17a secretion increased after the administration of Etanercept, and GAD65-induced cytokines and chemokines were also enhanced following 1 month of Etanercept administration.

Conclusions: Combination therapy with parallel treatment with GAD-alum, Etanercept and vitamin D in children and adolescents with type 1 diabetes was feasible and tolerable but had no beneficial effects on the autoimmune process or beta cell function.

Keywords: C-peptide; Etanercept; GAD-alum; immune intervention; type 1 diabetes; vitamin D.

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References

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