Catch-up growth during tocilizumab therapy for systemic juvenile idiopathic arthritis: Results from a phase iii trial

Fabrizio De Benedetti, Hermine Brunner, Nicolino Ruperto, Rayfel Schneider, Ricardo Xavier, Roger Allen, Diane E. Brown, Jeffrey Chaitow, Manuela Pardeo, Graciela Espada, Valeria Gerloni, Barry L. Myones, James W. Frane, Jianmei Wang, Terri H. Lipman, Kamal N. Bharucha, Alberto Martini, Daniel Lovell

Research output: Contribution to journalArticlepeer-review

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. Conclusion 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.

Original languageEnglish
Pages (from-to)840-848
Number of pages9
JournalArthritis and Rheumatology
Volume67
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Medicine(all)

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