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Title: Etanercept in Children With Juvenile Idiopathic Arthritis Spares Corticosteroids and Decreases Growth Retardation

URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R
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Clin Exp Rheumatol 2003;21:779-784. "Growth reconstitution in juvenile idiopathic arthritis treated with etanercept"
02/04/2004 09:11:00 AM
By Emma Hitt, PhD

The use of etanercept in children with juvenile idiopathic arthritis (JIA) spares corticosteroid use and, therefore, may decrease the risk of growth retardation, according to a new report. Growth failure is an important problem in patients with uncontrolled JIA; this condition also affects 10% of patients not treated with corticosteroids. The precise aetiology of growth retardation is unknown, but an influence of proinflammatory cytokines on the neuroendocrine axis insulin-like growth factor (IGF) production has been postulated. In their study, Heinrike Schmeling, MD, with the Department of Pediatrics at the Martin-Luther University Halle-Wittenberg, Germany and colleagues evaluated the effects of highly active antirheumatic treatment with the tumour necrosis factor antagonist etanercept on growth retardation. Out of 18 patients, 7 with refractory juvenile idiopathic arthritis demonstrated growth retardation leading to short stature. Over the course of 2 years, the researchers measured antropometric markers and disease activity parameters--including the number of swollen and tender joints, morning stiffness, erythrocyte sedimentation rate and C reactive protein levels. These values were monitored monthly during the first year of treatment and every 3 months thereafter. Serum levels of IGF-1 and IFG-BP were also measured. Treatment with etanercept increased growth velocity significantly from 3.7cm before the beginning of the therapy to 7.6 cm in the first year of treatment ([P < .001). The average length-standard-deviation-score (SDS) increased from -2.4 to -1.9 after one year and to -1.1 after two years (P = .05) suggesting that catch-up growth was occurring. Before 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 < .001). IGF-1 serum level and CRP levels were inversely correlated. "In conclusion, the activity of the inflammatory process was the most important growth-impairing factor and glucocorticosteroids aggravated only this effect," the researchers note. They suggest that the effect of etanercept 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. "Therapy with etanercept allows to control the inflammatory process and therefore also to spare corticosteroids," Dr. Schmeling and colleagues explain. "In JIA patients with growth delay, highly active antirheumatic therapy should be instituted before growth hormone substitution is considered and growth failure should be included in the evaluation of antirheumatic treatment," they add.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R
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