Etanercept Treatment in Children With New-Onset Type 1 Diabetes: Pilot randomized, placebo-controlled, double-blind study

• Published in: Diabetes care Vol. 32; no. 7; pp. 1244 - 1249
• Main Authors: MASTRANDREA, Lucy, YU, Jihnhee, BEHRENS, Torsten, BUCHLIS, John, ALBINI, Christine, FOURTNER, Shannon, QUATTRIN, Teresa
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2009
• Subjects: Adolescent; Biological and medical sciences; Blood; c-peptide; C-Peptide - metabolism; Cells; Child; Child, Preschool; children; Children & youth; Chronic illnesses; Complications and side effects; Diabetes; Diabetes. Impaired glucose tolerance; Disease; Dosage and administration; Double-Blind Method; drug effects; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etanercept; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feasibility Studies; Female; Glycated Hemoglobin; Glycated Hemoglobin A - drug effects; Glycated Hemoglobin A - metabolism; Health aspects; Hospitalization; Hospitals; Humans; Hypoglycemic Agents; Hypoglycemic Agents - therapeutic use; Immunoglobulin G; Immunoglobulin G - therapeutic use; immunology; Immunosuppressive Agents; Immunosuppressive Agents - therapeutic use; Insulin; Insulin - metabolism; Insulin - therapeutic use; Insulin Secretion; insulin-dependent diabetes mellitus; Insulin-Secreting Cells; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Islets of Langerhans; Islets of Langerhans - immunology; leukocyte count; liver; Male; Medical sciences; Metabolic diseases; metabolism; Miscellaneous; Monoclonal antibodies; Original Research; Patient Selection; patients; Physical examinations; Physiological aspects; Pilot Projects; Placebos; Public health. Hygiene; Public health. Hygiene-occupational medicine; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor - therapeutic use; renal function; Rodents; secretion; therapeutic use; therapeutics; Type 1 diabetes; women; Womens health; United States; Endocrinopathy; Human; Immunopathology; Nutrition; Cytokine; Autoimmune disease; Metabolic diseases; Early stage; Anti-Tumor Necrosis Factor-alpha; Immunomodulator; Randomization; Treatment; Etanercept; Type 1 diabetes; Anticytokine; Double blind study; Antagonist; Fusion protein; Child; Tumor necrosis factor α; Endocrinology
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc09-0054

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. 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. 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. 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.