Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, double-blind study

Lucy Mastrandrea, Jihnhee Yu, Torsten Behrens, John Buchlis, Christine Albini, Shannon Fourtner, Teresa Quattrin, Lucy Mastrandrea, Jihnhee Yu, Torsten Behrens, John Buchlis, Christine Albini, Shannon Fourtner, Teresa Quattrin

Abstract

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.

Research design and 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.

Trial registration: ClinicalTrials.gov NCT00730392.

Figures

Figure 1
Figure 1
Flow diagram showing the progress of the patients throughout the trial.
Figure 2
Figure 2
A1C values (A) and relative change in A1C (B) throughout a 24-week treatment and 12-week washout period for etanercept- and placebo-treated groups. Values represent means ± SEM at each time point. *P ≤ 0.05; ⋁P ≤ 0.01. ♦, placebo; ■, etanercept.
Figure 3
Figure 3
C-peptide at baseline and 24 weeks for individual subjects. ●, etanercept; ○, placebo.

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