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

Ludvigsson, Johnny ; Routray, Indusmita ; Vigård, Tore LU ; Hanås, Ragnar ; Rathsman, Björn ; Carlsson, Annelie LU orcid ; Särnblad, Stefan ; Albin, Anna Karin LU ; Arvidsson, Carl Göran and Samuelsson, Ulf , et al. (2021) In Diabetes/Metabolism Research and Reviews 37(7).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C-peptide, Etanercept, GAD-alum, immune intervention, type 1 diabetes, vitamin D
in
Diabetes/Metabolism Research and Reviews
volume
37
issue
7
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:33486892
  • scopus:85101003169
ISSN
1520-7552
DOI
10.1002/dmrr.3440
language
English
LU publication?
yes
id
adc3abb3-ad4d-4fba-97f7-8b89a4aad7a6
date added to LUP
2021-03-03 07:28:02
date last changed
2024-06-14 10:34:06
@article{adc3abb3-ad4d-4fba-97f7-8b89a4aad7a6,
  abstract     = {{<p>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.</p>}},
  author       = {{Ludvigsson, Johnny and Routray, Indusmita and Vigård, Tore and Hanås, Ragnar and Rathsman, Björn and Carlsson, Annelie and Särnblad, Stefan and Albin, Anna Karin and Arvidsson, Carl Göran and Samuelsson, Ulf and Casas, Rosaura}},
  issn         = {{1520-7552}},
  keywords     = {{C-peptide; Etanercept; GAD-alum; immune intervention; type 1 diabetes; vitamin D}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{7}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Diabetes/Metabolism Research and Reviews}},
  title        = {{Combined Etanercept, GAD-alum and vitamin D treatment : an open pilot trial to preserve beta cell function in recent onset type 1 diabetes}},
  url          = {{http://dx.doi.org/10.1002/dmrr.3440}},
  doi          = {{10.1002/dmrr.3440}},
  volume       = {{37}},
  year         = {{2021}},
}