Catch-up growth during tocilizumab therapy for systemic juvenile idiopathic arthritis: results from a phase III trial.

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.

Age of thelarche and menarche in contemporary US females: a cross-sectional analysis.

AIM: A recent secular trend towards earlier thelarche has been suggested. The aim of this study is to examine normative ages of thelarche and menarche in contemporary US females. METHODS: Trained physicians documented Tanner breast stage by observation in a cross-sectional cohort. Age of menarche was self-reported. The subjects were healthy female children and adolescents. The mean age of thelarche was determined by probit analysis and the mean age of menarche was determined by using a normal time-to-event model. RESULTS: Mean age of thelarche was 9.7 years among 610 females aged 3.0-17.9 years (70% non-Hispanic Caucasian (NHC), 14% African-Americans, 7% Hispanic, 9% "other"). The mean age of menarche was 12.8 years for NHC, with African-Americans having menarche 0.6 years earlier. CONCLUSIONS: Thelarche occurred earlier than recently reported, while age of menarche remained unchanged, this supported a persistent secular trend towards earlier thelarche but stable age of menarche. This suggests that the observed thelarche is gonadotropin-independent or the tempo of pubertal advancement has slowed.

Characteristics of children with the best and poorest first- and second-year growth during rhGH therapy: data from 25 years of the Genentech national cooperative growth study (NCGS).

BACKGROUND: Models assessing characteristics contributing to response to recombinant human growth hormone (rhGH) response rarely address growth extremes in both years 1 and 2 or examine how children track from year to year. Using National Cooperative Growth Study (NCGS) data, we determined characteristics contributing to responsiveness to rhGH and the pattern of change from years 1 to 2. PATIENTS AND METHODS: Height velocity standard deviation score (HV SDS) for 2 years for prepubertal children with idiopathic GH deficiency (IGHD) (n = 1899) and idiopathic short stature (ISS) (n = 1186) treated with similar doses for two years were computed. Group 1 = HV SDS < -1; 2 = HV SDS -1 to +1; 3 = HV SDS > +1. RESULTS: For IGHD, mean age was 7.5 years and similar in all groups. Year 1 HV SDS was associated with greater body mass index (BMI) SDS, lower pre-treatment HV, baseline height SDS, greater target height SDS minus height SDS, and lower maximum stimulated GH (P <0.0001). Year 2, 172/271 (73%) in group 1 moved to either group 2 (n = 156) or 3 (n = 16). Year 2 HV SDS was associated with greater year 1 HV SDS (r = 0.045, P <0.0001), greater BMI SDS, taller parents and lower peak GH.For ISS, year 1 HV SDS was associated with greater BMI SDS and lower pre-treatment HV (P ≤0.0001). 109/169 (64%) in group 1 moved to group 2 (n = 90) or group 3 (n = 19). Greater year 2 HV SDS was related to year 1 HV SDS (r = 0.27, P <0.0001). CONCLUSION: For IGHD, multiple characteristics contributed to best first-year response but for ISS, best first-year HV SDS was associated only with BMI SDS and inversely with pre-treatment HV. For both GHD and ISS, year 1 HV SDS was not a strong enough predictor of year 2 HV SDS to use first-year HV alone to determine GH continuation.