Abstract

Objective: To gather preliminary data on the feasibility and efficacy of etanercept therapy to prolong endogenous insulin production in newly diagnosed pediatric patients with type 1 diabetes mellitus.

Research design and Methods: A 24-week double-blind, randomized, placebo-controlled study conducted at the Diabetes Center, Women and Children's Hospital of Buffalo. Eighteen subjects (11M/7F, age 7.8-18.2 years) were randomized to receive either placebo (P) or etanercept (E). Inclusion criteria included age 3-18 years, GAD-65 and/or ICA positivity, HbA1c above 6%, 3 insulin injections per day, WBC 3,000-10,000, platelets >100,000, and normal liver and renal function. Intention to treat analysis was used.

Results: HbA1c at week 24 was lower in the etanercept (5.91 ± 0.5%) compared to placebo group (6.98 ± 1.2%; p<0.05) with a higher percent decrease from baseline compared to the placebo (E 0.41 ± 0.1 vs. P 0.18 ± 0.21; p<0.01). The percent change in c-peptide AUC 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 to 23% increase in the placebo group (p<0.05). Seventeen patients completed, none withdrew because of adverse events.

Conclusions: In this small pilot study, treatment of pediatric patients newly diagnosed with type 1 diabetes mellitus with etanercept resulted in lower HbA1c, increased endogenous insulin production, suggesting preservation of beta cell function. A larger study is needed to further explore safety and efficacy.