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Growth reconstitution in juvenile idiopathic arthritis treated with etanercept

H Schmeling1, E Seliger, G Horneff

  • 1Department of Pediatrics, Martin-Luther University Halle-Wittenberg, Halle, Germany.

Clinical and Experimental Rheumatology
|January 27, 2004
PubMed

Insights

Tumor necrosis factor antagonist therapy significantly improved growth velocity and catch-up growth in children with juvenile idiopathic arthritis. This treatment may counteract the inhibitory effects of inflammatory cytokines on insulin-like growth factor production.

Area of Science:

  • Pediatric Rheumatology
  • Endocrinology
  • Inflammatory Diseases

Background:

  • Growth failure is a significant complication in juvenile idiopathic arthritis (JIA), affecting up to 10% of patients not treated with corticosteroids.
  • Proinflammatory cytokines like TNF-alpha, IL-1beta, and IL-6 are suspected to impair neuroendocrine function and insulin-like growth factor (IGF) production, contributing to growth retardation in JIA.

Purpose of the Study:

  • To evaluate the efficacy of tumor necrosis factor (TNF) antagonist therapy, specifically etanercept, in improving growth retardation in children with refractory JIA.
  • To assess the impact of etanercept on growth parameters and serum levels of IGF-1 and IGF binding protein-3 (IGF-BP-3).

Main Methods:

  • Monthly anthropometric measurements and disease activity assessments (joint counts, ESR, CRP) were conducted during the first year of etanercept treatment, followed by quarterly monitoring.
  • Serum levels of IGF-1 and IGF-BP-3 were measured before and during treatment.

Main Results:

  • Etanercept treatment led to a significant increase in growth velocity, from 3.7 cm/year to 7.6 cm/year (p < 0.001).
  • The length-standard-deviation-score (SDS) improved significantly, indicating catch-up growth (from -2.4 to -1.1 after two years, p = 0.05).
  • Serum levels of IGF-1 and IGF-BP-3 increased significantly with treatment (p < 0.001), showing an inverse correlation between IGF-1 and CRP levels.

Conclusions:

  • Intensified anti-inflammatory treatment with etanercept positively impacts growth in children with uncontrolled JIA.
  • The beneficial effect on growth may stem from the reversal of cytokine-induced inhibition of IGF-1 and IGF-BP-3 synthesis.
  • Growth failure assessment should be an integral part of evaluating antirheumatic treatment efficacy in JIA.
Abstract

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