Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, double-blind study.
OBJECTIVE
To gather preliminary data on the feasibility and efficacy of etanercept therapy to prolong endogenous insulin production in pediatric patients with newly diagnosed type 1 diabetes.


METHODS
This was a 24-week double-blind, randomized, placebo-controlled study conducted at the Diabetes Center, Women and Children's Hospital of Buffalo. Eighteen subjects (11 male and 7 female, aged 7.8-18.2 years) were randomly assigned to receive either placebo or etanercept. Inclusion criteria included age 3-18 years, GAD-65 and/or islet cell antibody positivity, A1C >6%, three insulin injections per day, white blood cell count 3,000-10,000, platelets >100,000, and normal liver and renal function. Intention-to-treat analysis was used.


RESULTS
A1C at week 24 was lower in the etanercept group (5.91 +/- 0.5%) compared with that in the placebo group (6.98 +/- 1.2%; P < 0.05) with a higher percent decrease from baseline than in the placebo group (etanercept 0.41 +/- 0.1 vs. placebo 0.18 +/- 0.21; P < 0.01). The percent change in C-peptide area under the curve from baseline to week 24 showed a 39% increase in the etanercept group and a 20% decrease in the placebo group (P < 0.05). From baseline to week 24 insulin dose decreased 18% in the etanercept group compared with a 23% increase in the placebo group (P < 0.05). Seventeen patients completed the study, and none withdrew because of adverse events.


CONCLUSIONS
In this small pilot study, treatment of pediatric patients newly diagnosed with type 1 diabetes with etanercept resulted in lower A1C and increased endogenous insulin production, suggesting preservation of beta-cell function. A larger study is needed to further explore safety and efficacy.
Department of Pediatrics, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
Lucy
L
Mastrandrea
Jihnhee
J
Yu
Torsten
T
Behrens
John
J
Buchlis
Christine
C
Albini
Shannon
S
Fourtner
Teresa
T
Quattrin
D000293:Adolescent; D002096:C-Peptide / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D000068800:Etanercept; D005240:Feasibility Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D018579:Patient Selection; D010865:Pilot Projects; D010919:Placebos; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*
D002096:C-Peptide; D000068800:Etanercept; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007328:Insulin; D010919:Placebos; D018124:Receptors, Tumor Necrosis Factor