title: Catch-up growth during tocilizumab therapy for systemic juvenile idiopathic arthritis: results from a phase III trial.
abstract: OBJECTIVE
  To investigate the impact of tocilizumab treatment on growth and growth-related laboratory parameters in patients with systemic juvenile idiopathic arthritis (JIA) enrolled in a phase III clinical trial.
  
  
  METHODS
  Patients with systemic JIA ages 2-17 years (n = 112) received tocilizumab in a 12-week, randomized, placebo-controlled period and a long-term open-label extension. Height velocity and standard deviation (SD) score; levels of insulin-like growth factor 1 (IGF-1), osteocalcin (OC), and C-telopeptide of type I collagen (CTX-I); and Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71) were measured in a post hoc analysis of 83 patients who never received growth hormone and did not reach Tanner stage 5 by the end of the first year of treatment.
  
  
  RESULTS
  Patients had stunted growth at baseline (mean height SD score -2.2). During tocilizumab treatment, males (73%) and females (83%) experienced above-normal mean height velocities of 6.6 cm/year (P < 0.0001 versus World Health Organization norms). Mean height SD score increases during year 1 (0.29) and year 2 (0.31) were significant (both P < 0.0001). The mean SD score for IGF-1 levels increased significantly (-0.2 for year 1 and -0.1 for year 2 versus -1.0 at baseline; both P < 0.0001). Mean OC and CTX-I levels (both P < 0.0001) and the OC:CTX-I ratio (P = 0.014) significantly increased from baseline to year 2. In multiple regression analysis, first-year height velocity had a significant inverse relationship to JADAS-71 at year 1, age, mean glucocorticoid dosage during the year, and height SD score at baseline.
  
  
  CONCLUSIONS
  Our findings indicate that during treatment with tocilizumab, patients with systemic JIA experience significant catch-up growth, normalization of IGF-1 levels, and bone balance improvement favoring bone formation.
authors.affiliation: IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
authors.forename: Hermine
authors.initials: H
authors.lastname: Brunner
authors.forename: Nicolino
authors.initials: N
authors.lastname: Ruperto
authors.forename: Rayfel
authors.initials: R
authors.lastname: Schneider
authors.forename: Ricardo
authors.initials: R
authors.lastname: Xavier
authors.forename: Roger
authors.initials: R
authors.lastname: Allen
authors.forename: Diane E
authors.initials: DE
authors.lastname: Brown
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chaitow
authors.forename: Manuela
authors.initials: M
authors.lastname: Pardeo
authors.forename: Graciela
authors.initials: G
authors.lastname: Espada
authors.forename: Valeria
authors.initials: V
authors.lastname: Gerloni
authors.forename: Barry L
authors.initials: BL
authors.lastname: Myones
authors.forename: James W
authors.initials: JW
authors.lastname: Frane
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wang
authors.forename: Terri H
authors.initials: TH
authors.lastname: Lipman
authors.forename: Kamal N
authors.initials: KN
authors.lastname: Bharucha
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Daniel
authors.initials: D
authors.lastname: Lovell
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D024042:Collagen Type I / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D015675:Osteocalcin / Q000097:blood*; D010455:Peptides / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; C502936:tocilizumab