Growth During Tocilizumab Therapy for Polyarticular-course Juvenile Idiopathic Arthritis: 2-year Data from a Phase III Clinical Trial.

Objective: Evaluate growth in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ) for up to 2 years in a phase III trial.

Methods: Patients with pcJIA lasting at least 6 months and inadequate response to methotrexate received open-label TCZ intravenously every 4 weeks (randomly assigned to 8 or 10 mg/kg if they weighed < 30 kg; received 8 mg/kg if they weighed ≥ 30 kg) for 16 weeks. Patients with JIA American College of Rheumatology 30 response at Week 16 were randomly assigned to TCZ or placebo for 24 weeks, with an open-label extension through Week 104.

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.

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.

Adult and near-adult height in patients with severe insulin-like growth factor-I deficiency after long-term therapy with recombinant human insulin-like growth factor-I.

Background: Treatment with recombinant human insulin-like growth factor-I (IGF-I) stimulates linear growth in children with severe IGF-I deficiency (IGFD).

Aims: To evaluate the efficacy and safety of treatment with IGF-I in patients with severe IGFD treated until adult or near-adult height.

Methods: Twenty-one children with severe IGFD were treated until adult or near-adult height under a predominantly open-label design.

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.

A method to determine the likelihood of transition to puberty in a heterogeneous prepubertal age group.

A model based on pubertal status and age in normal healthy children that can be used to estimate the probability that a given child will enter or progress through puberty in a given period is presented. This model could also be used to estimate the proportion of children who would be expected to have changes in their pubertal status over a given period, for example, in an interventional trial of growth promoting agents.

Is there "seasonal" variation in height velocity in children treated with growth hormone? Data from the National Cooperative Growth Study.

Background: Growth rate In children is reported to have seasonal variability. There are fewer published data regarding seasonal variability while on growth hormone (GH) therapy, and none analyzing growth rate with respect to number of daylight hours.

Methods: We analyzed 11,587 3-month intervals in 2277 prepubertal children (boys ages 3-14 years, girls ages 3-12 years) with idiopathic GH deficiency from the National Cooperative Growth Study (NCGS) database.

Intracranial hypertension in pediatric patients treated with recombinant human growth hormone: data from 25 years of the Genentech National Cooperative Growth Study.

Intracranial hypertension (IH) is a rare condition in children. However, a relationship between recombinant human growth hormone (rhGH) therapy and IH has been well documented. Risk factors were assessed for 70 rhGH-naive patients enrolled in the National Cooperative Growth Study with reports of IH after treatment initiation.

First-year response to rhGH therapy in children with CKD: a National Cooperative Growth Study Report.

A clear definition of the appropriate growth response during recombinant human growth hormone (rhGH) treatment has never been established in the pediatric chronic kidney disease (CKD) population. We present here data from Genentech's National Cooperative Growth Study (NCGS) on the first-year growth response in prepubertal children with CKD. Using NCGS data, we constructed response curves for the first year of rhGH therapy in 270 (186 males, 84 females) naïve-to-treatment, prepubertal children with CKD prior to transplant or dialysis.

Recombinant insulin-like growth factor (IGF)-I treatment in short children with low IGF-I levels: first-year results from a randomized clinical trial.

Context: Short stature in children may be associated with low IGF-I despite normal stimulated GH levels and without other causes.

Objective: Our objective was to assess the safety and efficacy of recombinant human IGF-I (rhIGF-I) in short children with low IGF-I levels.

Design: This was a 1-yr, randomized, open-label trial (MS301).

A stepwise increase in recombinant human growth hormone dosing during puberty achieves improved pubertal growth: a National Cooperative Growth Study report.

Unlabelled: The magnitude of the pubertal growth spurt contributes to adult height. Children treated with increased doses of recombinant human growth hormone (rhGH) during puberty have shown improved near adult height (NAH) outcomes that varied by treatment duration.

Methods: Males, in a single clinic, treated with a prepubertal dose of rhGH (0.

Growth hormone responsiveness: peak stimulated growth hormone levels and other variables in idiopathic short stature (ISS): data from the National Cooperative Growth Study.

Hypothesis: In children with idiopathic short stature (ISS), growth hormone (GH) response to a provocative test will be inversely related to the first year response to hGH and be a variable accounting for a degree of responsiveness.

Background: Because high levels of GH are a characteristic of GH insensitivity, such as in Laron syndrome, it is possible that a high stimulated GH is associated with a lower first year height velocity among children diagnosed as having ISS.

Methods: We examined the relationship between the peak stimulated GH levels in 3 ISS groups; GH >10 -<25, 25-40, and >40 ng/mL and the first year growth response to rhGH therapy.

Induced pluripotent stem cell lines derived from human somatic cells.

Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells. These induced pluripotent human stem cells have normal karyotypes, express telomerase activity, express cell surface markers and genes that characterize human ES cells, and maintain the developmental potential to differentiate into advanced derivatives of all three primary germ layers.

Height velocity targets from the national cooperative growth study for first-year growth hormone responses in short children.

Context: Although GH has been used to treat short stature in GH deficiency (GHD) and other conditions for more than 40 yr, criteria for satisfactorily defining targets for GH responsiveness have never been developed.

Objective: The objective of this study was to present the first-year growth expressed as height velocity (HV) for prepubertal boys and girls with idiopathic GHD, organic GHD, idiopathic short stature, or Turner syndrome from Genentech's National Cooperative Growth Study to derive age-specific targets for GH responsiveness for each etiology and gender.

Design And Population: Using data from the National Cooperative Growth Study, we constructed curves of response to GH during the first year of treatment with standard daily doses in naive-to-treatment prepubertal children with idiopathic GHD (2323 males, 842 females), organic GHD (582 males, 387 females), idiopathic short stature (1392 males, 465 females), or Turner syndrome (1367 females).

Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity.

Context: Children with severe IGF-I deficiency due to congenital or acquired defects in GH action have short stature that cannot be remedied by GH treatment.

Objectives: The objective of the study was to examine the long-term efficacy and safety of recombinant human IGF-I (rhIGF-I) therapy for short children with severe IGF-I deficiency.

Design: Seventy-six children with IGF-I deficiency due to GH insensitivity were treated with rhIGF-I for up to 12 yr under a predominantly open-label design.

Derivation of human embryonic stem cells in defined conditions.

We have previously reported that high concentrations of basic fibroblast growth factor (bFGF) support feeder-independent growth of human embryonic stem (ES) cells, but those conditions included poorly defined serum and matrix components. Here we report feeder-independent human ES cell culture that includes protein components solely derived from recombinant sources or purified from human material. We describe the derivation of two new human ES cell lines in these defined culture conditions.

A brief review of the use and utility of growth hormone stimulation testing in the NCGS: do we need to do provocative GH testing?

True growth hormone deficiency (GHD) in childhood, while rare, has major clinical consequences. GHD is often associated with other pituitary hormone deficiencies, so these children may require multiple hormonal replacement and close clinical follow-up to optimize their outcome. Growth hormone stimulation testing (GHST), as currently conducted, is not a reliable diagnostic tool.

Efficacy and safety results of long-term growth hormone treatment of idiopathic short stature.

Context: Small clinical trials of GH treatment of idiopathic short stature (ISS) show variable efficacy.

Objective: The study was an analysis of a large GH registry for efficacy and safety of GH treatment of ISS. There was also a comparison with a specific clinical trial.

Growth hormone therapy of Turner syndrome: the impact of age of estrogen replacement on final height. Genentech, Inc., Collaborative Study Group.

Clinical trials of recombinant human GH therapy in Turner syndrome that began more than a decade ago show that GH accelerates the linear growth rate. Several studies indicate that final height is also improved, although the magnitude of the increase has been debated. The age at which feminization is induced could be an important factor in determining the patient's ultimate growth response.

Body mass index (BMI) in Turner Syndrome before and during growth hormone (GH) therapy.

Objective: To study whether body mass index (BMI) is different in girls with Turner syndrome (TS) compared to normal girls, and whether BMI in TS is affected by growth hormone (GH) treatment.

Design: A retrospective cross-sectional study.

Subjects: 2468 girls with TS enrolled in the National Cooperative Group Study (NCGS), a collaborative surveillance study for assessing GH-treated children.

Effects of chronic renal failure and growth hormone on serum levels of insulin-like growth factor-binding protein-4 (IGFBP-4) and IGFBP-5 in children: a report of the Southwest Pediatric Nephrology Study Group.

Children with chronic renal failure (CRF) have high serum levels of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), -2, and -6. The excess IGFBP-2 and -1 may play a role in the growth failure of CRF children by sequestering IGF peptides. In contrast, IGFBP-3 levels rise with GH treatment of CRF children, suggesting a role for IGFBP-3 in their accelerated growth.

Metabolic consequences of 5-year growth hormone (GH) therapy in children treated with GH for idiopathic short stature. Genentech Collaborative Study Group.

In a multicenter study the metabolic effects of 5 yr of GH therapy in children with idiopathic short stature were evaluated. Patients received 0.3 mg/kg.

Growth hormone therapy of Turner's syndrome: beneficial effect on adult height.

Objective: To carry out a multicenter, prospective, randomized trial of human growth hormone (GH), alone or in combination with oxandrolone (OX), in patients with Turner's syndrome (TS).

Methods: In an initial phase lasting 12 to 24 months, 70 girls with TS, verified by karyotype, were randomly assigned to one of four groups: (1) observation, (2) OX, (3) GH, or (4) GH plus OX. After completion of the first phase, group 3 subjects continued to receive GH only.

Insulin-like growth factor-binding protein-6 levels are elevated in serum of children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band.

Modulation of growth factors by growth hormone in children with chronic renal failure. The Southwest Pediatric Nephrology Study Group.

Anthropometric measurements and circulating growth factors were studied serially in 44 prepubertal children with growth failure and chronic renal failure (GFR = 10 to 40 ml/min/1.73 m2) who were randomized to receive either recombinant human growth hormone (rhGH; N = 30) or no treatment (N = 14). RhGH was given as Nutropin, 0.