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Pharmacological Research Jul 2023We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations... (Meta-Analysis)
Meta-Analysis Review
Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis.
We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.
Topics: Humans; Child; Human Growth Hormone; Growth Hormone; Quality of Life; Cost-Benefit Analysis; Dwarfism, Pituitary; Hormone Replacement Therapy
PubMed: 37236413
DOI: 10.1016/j.phrs.2023.106805 -
The Journal of Clinical Endocrinology... Jul 2023The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited.
CONTEXT
The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited.
OBJECTIVE
This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes.
DESIGN
A prospective, observational, posttrial study (NCT03290235).
SETTING, PARTICIPANTS AND INTERVENTION
Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to <0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months.
MAIN OUTCOMES MEASURES
Height SD score (Ht SDS) at 12, 24, and 36 months.
RESULTS
A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred.
CONCLUSIONS
PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.
Topics: Humans; Child; Prospective Studies; Human Growth Hormone; Growth Disorders; Dwarfism, Pituitary; Insulin-Like Growth Factor I; Polyethylene Glycols; Recombinant Proteins
PubMed: 36669772
DOI: 10.1210/clinem/dgad039 -
The Journal of Clinical Endocrinology... Sep 2023Growth hormone deficiency (GHD) in children is currently treated with daily injections of GH, which can be burdensome for patients and their parents/guardians....
CONTEXT
Growth hormone deficiency (GHD) in children is currently treated with daily injections of GH, which can be burdensome for patients and their parents/guardians. Somapacitan is a GH derivative in development for once-weekly treatment of GHD.
OBJECTIVE
This work aimed to assess the efficacy and safety of somapacitan, and associated disease/treatment burden, after 4 years of treatment and 1 year after switching to somapacitan from daily GH.
METHODS
This long-term safety extension of a multicenter, controlled phase 2 trial (NCT02616562) took place at 29 sites in 11 countries. Patients were prepubertal, GH-naive children with GHD. Fifty patients completed 4 years of treatment. Patients in the pooled group received somapacitan (0.04, 0.08, 0.16 mg/kg/week) for 1 year, followed by the highest dose (0.16 mg/kg/week) for 3 years. Patients in the switched group received daily GH 0.034 mg/kg/day for 3 years, then somapacitan 0.16 mg/kg/week for 1 year. Main outcome measures were height velocity (HV), change from baseline in HV SD score (SDS), change from baseline in height SDS, disease burden, and treatment burden for patients and parents/guardians.
RESULTS
Changes from baseline in HV and HV SDS were similar and as expected in both groups. Observer-reported outcomes showed that patients and parents/guardians seem to have experienced a reduced treatment burden when switching from daily GH to somapacitan. Most parents/guardians (81.8%) strongly/very strongly preferred somapacitan over daily GH.
CONCLUSIONS
Somapacitan showed similar efficacy and safety in patients who continued somapacitan treatment and those who switched from daily GH to somapacitan. Once-weekly injections may lead to a reduced treatment burden relative to once-daily injections. A plain-language summary of this work is available.
Topics: Child; Humans; Body Height; Drug Administration Schedule; Dwarfism, Pituitary; Human Growth Hormone; Insulin-Like Growth Factor I; Treatment Outcome
PubMed: 36995872
DOI: 10.1210/clinem/dgad183 -
The Journal of Clinical Endocrinology... Nov 2023Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD). (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD).
OBJECTIVE
Evaluate the efficacy and tolerability of somapacitan in children with GHD after 2 years of treatment and after the switch from daily GH.
DESIGN
A randomized, multinational, open-labelled, controlled parallel group phase 3 trial, comprising a 52-week main phase and 3-year safety extension (NCT03811535).
SETTING
Eighty-five sites across 20 countries.
PATIENTS
A total of 200 treatment-naïve prepubertal patients were randomized and exposed; 194 completed the 2-year period.
INTERVENTIONS
Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (0.034 mg/kg/d) during the first year, after which all patients received somapacitan 0.16 mg/kg/wk.
MAIN OUTCOME MEASURES
Height velocity (HV; cm/year) at week 104. Additional assessments included HV SD score (SDS), height SDS, IGF-I SDS, and observer-reported outcomes.
RESULTS
HV was sustained in both groups between 52 and 104 weeks. At week 104, mean (SD) for HV between weeks 52 and 104 was 8.4 (1.5) cm/year after continuous somapacitan treatment and 8.7 (1.8) cm/year after 1 year of somapacitan treatment following switch from daily GH. Secondary height-related endpoints also supported sustained growth. Mean IGF-I SDS during year 2 was similar between groups and within normal range (-2 to +2). Somapacitan was well tolerated, with no safety or tolerability issues identified. GH patient preference questionnaire results show that most patients and their caregivers (90%) who switched treatment at year 2 preferred once-weekly somapacitan over daily GH treatment.
CONCLUSIONS
Somapacitan in children with GHD showed sustained efficacy and tolerability for 2 years, and after switching from daily GH. Patients/caregivers switching from daily GH expressed a preference for somapacitan.
CLINICAL TRIAL REGISTRATION
NCT03811535.
Topics: Humans; Child; Insulin-Like Growth Factor I; Human Growth Hormone; Growth Hormone; Growth Disorders; Dwarfism, Pituitary; Body Height
PubMed: 37406251
DOI: 10.1210/clinem/dgad394 -
Frontiers in Endocrinology 2023Isolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth...
OBJECTIVE
Isolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth hormone therapy is indicated. Here, our objective was to identify predictors of permanent GHD.
DESIGN
Retrospective single-centre study of patients with childhood-onset GHD who were re-tested after adult height attainment.
METHODS
Auxological, clinical, laboratory, and MRI data throughout follow-up were collected.
RESULTS
We included 101 patients. At GH treatment initiation, age was 8.1 ± 0.4 years, height -2.25 ± 0.8, and BMI -0.27 ± 0.1 SDS. The 29 (28.7%) patients with persistent GHD had lower height SDS (-2.57 ± 0.1 vs. -2.11 ± 0.1, <0.001) and mean GH peaks (8.4 ± 1.0 vs.13.2 ± 0.5 mIU/L, <0.001) at GHD diagnosis; at adult height, they had lower IGF1 (232 ± 19.9 vs. 331 ± 9.1 ng/mL, <0.001) and higher BMI SDS (-0.15 ± 0.27 vs. -0.73 ± 0.13, <0.005). By multivariate analysis, the best predictive model included height and BMI SDS, both GH peaks, and MRI findings at diagnosis. Patients with height at diagnosis <-3 SDS had a 7.7 (95% IC 1.4-43.1, p=0.02) fold higher risk of persistent GHD after adjustment on BMI SDS. An abnormal pituitary region by MRI was the strongest single predictor (7.2 times, 95% CI 2.7-19.8) and after multivariate analysis adjustment for GH peaks and height SDS at diagnosis, the risk increased to 10.6 (1.8 - 61.3) times.
CONCLUSIONS
Height <-3 SDS at GHD diagnosis and pituitary MRI abnormalities should lead to a high index of suspicion for persistent GHD.
Topics: Adult; Child; Humans; Dwarfism, Pituitary; Human Growth Hormone; Hypopituitarism; Retrospective Studies
PubMed: 37881494
DOI: 10.3389/fendo.2023.1270845 -
Drug Design, Development and Therapy 2024Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily... (Review)
Review
Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily injections. This daily treatment regimen often incurs a burden to patients and caregivers, leading to high rates of non-adherence and, consequently, decreased treatment efficacy outcomes. To address this shortcoming, long-acting growth hormones (LAGHs) have been developed with the aim of reducing the burden of daily injections, thereby potentially improving treatment adherence and outcomes. Somapacitan (Sogroya) (Novo Nordisk, Bagsværd, Denmark) is a LAGH currently approved for the treatment of adult and childhood GHD (AGHD and CGHD, respectively) in several countries. Other LAGHs, such as somatrogon (Ngenla) (Pfizer, New York, United States) and lonapegsomatropin/TransCon GH (Skytrofa) (Ascendis Pharma, Copenhagen, Denmark), are also currently approved and available for the treatment of CGHD in several countries. In this review, we will consider the method of protraction, pharmacokinetics (PK) and pharmacodynamics (PD), efficacy, and safety results of somapacitan in adult and pediatric trials and how these characteristics differ from those of the other aforementioned LAGHs. Additionally, the administration of somapacitan and timing of measurement of serum insulin-like growth factor-I (IGF-I) levels are summarized. Information on administration, advice on missed doses, and clinical guidelines are discussed, as well as identifying which patients are suitable for somapacitan therapy, and how to monitor and adjust dosing whilst on therapy.
Topics: Adult; Humans; Child; United States; Human Growth Hormone; Dwarfism, Pituitary; Growth Hormone; Treatment Outcome; Insulin-Like Growth Factor I; Histidine; Mannitol; Phenol
PubMed: 38333899
DOI: 10.2147/DDDT.S315172 -
Best Practice & Research. Clinical... Dec 2023Growth hormone (GH) deficiency (GHD) is one of the most prevalent deficiencies in patients with hypopituitarism and several cohort studies have demonstrated an increased... (Meta-Analysis)
Meta-Analysis Review
Growth hormone (GH) deficiency (GHD) is one of the most prevalent deficiencies in patients with hypopituitarism and several cohort studies have demonstrated an increased mortality risk in hypopituitary patients with a presumed GHD. The cause of the excess mortality is most likely multifactorial, including the etiology of the hypopituitarism, non-physiological replacement therapies (mostly glucocorticoid), tumor treatment and its side effects as well as untreated GHD. Several years later, other cohort studies that investigated life expectancy in patients with hypopituitarism on GH replacement therapy (GHRT) that showed a normalized mortality. By comparison of the distribution of characteristics of interest between cohorts, we discuss the existing literature to answer the following question: does growth hormone replacement really improve mortality rates in adult patients with hypopituitarism and GHD? We also conducted a meta-analysis of these studies. Since the literature suffers from selection and time bias (improvement of tumor management and other pituitary hormone replacement therapies), there is no high-quality evidence that replacement therapy for GHD really improves mortality. However, the available data does suggest that GHRT plays a significant part in the normalization of the mortality in patients with hypopituitarism.
Topics: Adult; Humans; Hypopituitarism; Dwarfism, Pituitary; Human Growth Hormone; Growth Hormone; Pituitary Neoplasms; Hormone Replacement Therapy
PubMed: 37914564
DOI: 10.1016/j.beem.2023.101835 -
Deutsches Arzteblatt International Feb 20243% of all children are unusually short, and 3% are unusually tall. New approaches have broadened the range of therapeutic options in treating growth disorders. (Review)
Review
BACKGROUND
3% of all children are unusually short, and 3% are unusually tall. New approaches have broadened the range of therapeutic options in treating growth disorders.
METHODS
This review is based on publications retrieved by a selective review of the literature and on the authors' clinical experience.
RESULTS
Pituitary growth hormone deficiency is treated with recombinant growth hormone. Long-acting preparations of this type became available recently, but their long-term safety and efficacy are still unknown. Vosoritide, a CNP analogue, has also been approved for the treatment of achondroplasia, and severe primary deficiency of insulin-like growth factor 1 (IGF-1) can be treated with recombinant IGF-1. In the treatment of excessively tall stature, new information on the safety of growth-attenuating treatment and an altered perception of above-average height in society have led to a change in management.
CONCLUSION
There are new options for the treatment of rare causes of short stature, while new information on the safety of treatment strategies for excessive tallness have led to a reconsideration of surgical intervention. There is insufficient evidence on the benefits and risks of supraphysiological GH therapy and of newer treatment options for which there are as yet no robust data on adult height. Therefore, before any treatment is provided, physicians should give patients and their families detailed information and discuss their expectations from treatment and the goals that treatment can be expected to achieve.
Topics: Child; Adult; Humans; Adolescent; Insulin-Like Growth Factor I; Human Growth Hormone; Growth Disorders; Dwarfism, Pituitary; Physicians
PubMed: 38051162
DOI: 10.3238/arztebl.m2023.0247 -
Best Practice & Research. Clinical... Dec 2023Daily administration of growth hormone (GH) treatment has been in clinical use for treatment for GH deficiency (GHD) in adults for more than 30 years. Numerous studies... (Review)
Review
Daily administration of growth hormone (GH) treatment has been in clinical use for treatment for GH deficiency (GHD) in adults for more than 30 years. Numerous studies have demonstrated evidence that GH treatment improves body composition, cardiovascular risk factors and quality of life with few side effects. Less frequent GH injections are hypothesized to improve adherence and several long-acting GH (LAGH) formulations have been developed and a few have been approved and marketed. Different pharmacological modifications have been applied and the pharmacokinetics and pharmacodynamics of LAGH are different to each other and to those of daily injections and require different dosing and monitoring specific for each LAGH. Studies have shown improved adherence with LAGH, and short-term efficacy and side effects are comparable between daily GH injections and LAGHs. Long-term treatment with daily GH injections is effective and safe, while long-term studies for LAGHs are awaited. In this review challenges, benefits, and risks of treatment with daily and long-acting GH preparations will be compared.
Topics: Adult; Humans; Growth Hormone; Quality of Life; Human Growth Hormone; Hypopituitarism; Dwarfism, Pituitary
PubMed: 37308376
DOI: 10.1016/j.beem.2023.101788 -
European Journal of Endocrinology Jul 2023Maternal inactivating GNAS mutations lead to pseudohypoparathyroidism 1A (PHP1A), newly classified as inactivating parathyroid hormone (PTH)/PTHrP-signaling disorder... (Observational Study)
Observational Study
BACKGROUND
Maternal inactivating GNAS mutations lead to pseudohypoparathyroidism 1A (PHP1A), newly classified as inactivating parathyroid hormone (PTH)/PTHrP-signaling disorder type 2 of maternal inheritance (iPPSD2). Patients present with resistance to PTH and other hormones, subcutaneous ossifications, brachydactyly, short stature, and early-onset obesity. They can be born small for gestational age (SGA) and may present with growth hormone (GH) deficiency. The use of recombinant human GH (rhGH) therapy has been sporadically reported, yet we lack data on the long-term efficacy and safety of rhGH, as well as on adult height.
OBJECTIVE
Our multicenter, retrospective, observational study describes growth in patients treated with rhGH in comparison with untreated iPPSD2/PHP1A controls.
METHODS
We included 190 patients, of whom 26 received rhGH. Height, weight, body mass index at various time points, and adult height were documented. We analyzed the effect of rhGH on adult height by using linear mixed models.
RESULTS
Adult height was available for 11/26 rhGH-treated individuals and for 69/164 controls. Patients treated with rhGH showed a gain in height of 0.7 standard deviation scores (SDS) after 1 year (CI +0.5 to +0.8, P < .001) and of 1.5 SDS after 3 years (CI +1.0 to +2.0, P < .001). Additionally, there was a clear beneficial impact of rhGH on adult height when compared with untreated controls, with a difference of 1.9 SDS (CI +1.1 to +2.7, P < .001). Body mass index SDS did not vary significantly upon rhGH therapy.
CONCLUSION
Recombinant human growth hormone treatment of iPPSD2/PHP1A patients with short stature improves growth and adult height. More studies are needed to confirm long-term efficacy and safety.
Topics: Humans; Adult; Growth Hormone; Retrospective Studies; Human Growth Hormone; Pseudohypoparathyroidism; Dwarfism, Pituitary; Hypopituitarism; Mutation; Body Height; Recombinant Proteins; Growth Disorders; Chromogranins; GTP-Binding Protein alpha Subunits, Gs
PubMed: 37440712
DOI: 10.1093/ejendo/lvad085