Catch-up Growth During Tocilizumab Therapy for Systemic Juvenile Idiopathic Arthritis: Results From a Phase III Trial

Arthritis Rheumatol. 2015 Mar;67(3):840-8. doi: 10.1002/art.38984.


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.

Trial registration: NCT00642460.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Arthritis, Juvenile / drug therapy*
  • Child
  • Child Development / drug effects*
  • Child, Preschool
  • Collagen Type I / blood*
  • Double-Blind Method
  • Female
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Osteocalcin / blood*
  • Peptides / blood*
  • Severity of Illness Index


  • Antibodies, Monoclonal, Humanized
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Insulin-Like Growth Factor I
  • tocilizumab

Associated data