2481 FernandezVojvodich, et al: Improved growth with etanercept Personal non-commercial use only. The Journal of Rheumatology Copyright © 2007. All rights reserved. Etanercept Treatment Improves Longitudinal Growth in Prepubertal Children with Juvenile Idiopathic Arthritis PAOLAFERNANDEZVOJVODICH,JESB.HANSEN,ULFANDERSSON,LARSSÄVENDAHL, andSTEFANHAGELBERG ABSTRACT. Objective. Anti-tumor necrosis factor (TNF) therapy is known to decrease disease activity of juvenile idiopathicarthritis(JIA),butitseffectonlongitudinalgrowthinrelationtopubertyisnotclear.Westud- iedlongitudinalgrowthinresponsetoetanercepttreatmentinprepubertalandpubertalpatientswithJIA. Methods. Out of 52 children treated with etanercept, we studied 20 prepubertal and 11 early/midpu- bertalpatientsadherenttotreatmentforatleast1year.Wecollecteddataongrowthandglucocorticoid medication and calculated each patient’s height standard deviation score (SDS) in relation to the mid- parental height, the change of this value (ΔhSDS) from –1 to 0 and 0 to 1 year of treatment, and the change between the ΔhSDS values to assess growth improvement. Results. Intheprepubertalgroup,therelativeheightSDS(mean±standarderrorofthemean)was–1.8 ±0.2,–2.1±0.3,and–1.9±0.3,andinthepubertalgroup–1.1±0.4,–1.3±0.3,and–1.1±0.3at–1, 0, and +1 year of treatment, respectively. The ΔhSDS before etanercept was –0.3 ± 0.1 in prepubertal and –0.2 ± 0.2 in pubertal patients. Over the first year with etanercept, ΔhSDS was +0.2 ± 0.1 in pre- pubertal(p=0.001vsbeforeetanercept;pairedStudentt-test)and+0.2±0.1inpubertalpatients(p= 0.071). Nevertheless, most prepubertal (17/20) and pubertal (8/11) patients had improved growth (ΔhSDS) in response to etanercept treatment when analyzed individually. The need for intraarticular glucocorticoid injections was negatively correlated to the improved growth (p = 0.001). Conclusion. TNF inhibition with etanercept improved growth in a majority of patients with JIA. Our data demonstrate that growth improvement with etanercept was independent of the pubertal growth spurt. (First Release Nov 15 2007; J Rheumatol 2007;34:2481–5) Key Indexing Terms: JUVENILEIDIOPATHICARTHRITIS ETANERCEPT GROWTH PUBERTY From the Pediatric Endocrinology and Pediatric Rheumatology Units, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden, and the Department of Epidemiology, Novo Nordisk A/S, Bagsvaerd, Denmark. Supported by the Swedish Research Council, Stiftelsen Frimurare Barnhuset i Stockholm, and unrestricted grants from Novo Nordisk A/S, Denmark and Wyeth AB, Sweden. P. Fernandez Vojvodich, BSc; L. Sävendahl, MD, PhD, Professor, Pediatric Endocrinology Unit; U. Andersson, MD, PhD, Professor; S. Hagelberg, MD, PhD, Pediatric Rheumatology Unit, Department of Woman and Child Health, Karolinska University Hospital; J.B. Hansen, MSc, PhD, Department of Epidemiology, Novo Nordisk A/S. Address reprint requests to Dr. S. Hagelberg, Pediatric Rheumatology Unit Q1:02, Department of Woman and Child Health, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. E-mail: Stefan.Hagelberg@karolinska.se Accepted for publication August 27, 2007. The introduction of anti-tumor necrosis factor (TNF) agents has revolutionized the treatment of rheumatoid arthritis (RA) in children and adults. Anti-TNF treatment leads to a signifi- cant decrease in disease activity in adult RA 1,2 and also in juvenile idiopathic arthritis (JIA) 3 , with sustained improve- mentandfewsideeffectsafter4years’followup 4 .Inpatients with RA undergoing anti-TNF treatment it has been shown that bone erosions are halted 5 , especially when the treatment is combined with methotrexate 6 (MTX). Etanercept is a recombinantfusionproteinbasedonthep75-receptorforTNF andtheFcpartofhumanimmunoglobulin.Itactsasasoluble receptor through competitive inhibition of the TNF-receptor on the cell surface, thereby diminishing TNF-driven inflam- mationthatplaysakeyroleinthearthriticprocess. Children who are affected by chronic inflammatory dis- eases may have stunted linear growth 7,8 . Data in rats suggest that TNF-α acts in synergy with interleukin 1ß to inhibit lin- ear bone growth 9 .Inasmallmixedpopulation(n=7)ofpre- pubertal and pubertal patients with refractory JIA and growth retardation, the institution of anti-TNF therapy was reported to be associated with growth reconstitution 10 .Arecentstudy, inalarger(n=71)populationofprepubertal/pubertalpatients with JIA, showed similar results of anti-TNF treatment on growth 11 . Our aim was to confirm these positive effects on growthinpatientswithJIAtreatedwithetanercept,analyzing theresponsesforprepubertalandpubertalpatientsseparately. MATERIALS AND METHODS Study patients. Between 1999 and 2004, treatment with Enbrel TM (etanercept) wasinitiatedin52ofourpatientswithJIA(PediatricRheumatologyUnit,Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden). These patients had previously shown an unsatisfactory response to treatmentwithnonsteroidalantiinflammatorydrugs,intraarticularcorticosteroid injections,andMTX,and/ordevelopedintolerablesideeffectstoMTX. www.jrheum.org Downloaded on December 2, 2021 from