Objective: Growth failure is a leading problem in uncontrolled juvenile idiopathic arthritis. It also affects 10% of patients who are not treated with corticosteroids. The influence of proinflammatory cytokines like interleukin-1 beta, interleukin-6 and tumour necrosis factor on the neuroendocrine axis as well as on the production of insulin-like growth factors (IGFs) has been postulated. The objective of the current study was to evaluate effects of highly active antirheumatic treatment with tumour necrosis factor antagonist on growth retardation. Seven out of 18 patients with refractory juvenile idiopathic arthritis treated with etanercept demonstrated growth retardation leading to short stature.
Methods: Antropometric measurements and disease activity parameters--including the number of swollen and tender joints, morning stiffness, ESR and CRP levels--were monitored monthly during the first year of treatment and every 3 months thereafter. Serum levels of IGF-1 and IFG-BP were measured as well.
Results: Upon treatment with etanercept, growth velocity increased from 3.7 +/- 1.2 cm before the beginning of the therapy to 7.6 +/- 1.2 cm in the first year of treatment (p < 0.001). The average length-standard-deviation-score (SDS) increased from -2.4 +/- 1.0 to -1.9 +/- 0.9 after one year and to -1.1 +/- 0.9 after two years (p = 0.05) indicating catch-up growth. Prior to the therapy, serum levels of insulin-like growth factor-1 and of insulin-like growth factor binding protein-3 were within the normal range but increased significantly upon treatment (p < 0.001). An inverse correlation of the IGF-1 serum level to CRP was found.
Conclusions: An intensified anti-inflammatory treatment using etanercept has a beneficial effect on growth in children with a so far uncontrolled inflammatory disease. This effect might be related to the cessation of the inhibitory effect of proinflammatory cytokines on the synthesis of IGF-1 and IGF-BP-3 in the liver. Growth failure should be included in the evaluation of antirheumatic treatment.