Compliance and Persistence in Pediatric and Adult Patients Receiving Growth Hormone Therapy

Rosenfeld, Ron G.; Bakker, Bert

doi:10.4158/ep.14.2.143

Cited by 171 publications

(196 citation statements)

References 19 publications

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“…In our study, there were no significant differences in each level of adherence between the two age groups. While, Rosenfeld et al [23] found a lower adherence level in the teen group (23%) in comparison with the children (36%) and adult groups (34%).…”

Section: Discussionmentioning

confidence: 88%

“…Rosenfeld et al [23] assessed 882 patients receiving or previously treated with GH using a questionnaire completed by patients and/or their parents. Adherence assessment was based on the responses to nine potential reasons for missing GH doses.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, Rosenfeld et al [23] reported that parents of highly compliant children had a lower educational level. In our study, there were no significant differences in each level of adherence between the two age groups.…”

Section: Discussionmentioning

confidence: 99%

“…The probable barriers to GH therapy adherence were assessed by a questionnaire, which was designed based on the reported results of the Rosenfeld et al study [23].…”

Section: Methodsmentioning

confidence: 99%

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Adherence to growth hormone therapy in children and its potential barriers

Mohseni

Heydari

Qorbani

et al. 2017

Journal of Pediatric Endocrinology and Metabolism

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Background: One of the main concerns in chronic diseases such as growth hormone (GH) deficiency is adherence to the treatment, which significantly affects treatment outcomes. Methods: This cross-sectional study was conducted among 169 GH recipient children (2-12 years) and teens (13-19 years) referred to a GH distributing teaching pharmacy. The eight-item Morisky Medication Adherence Scale (MMAS) and auto-compliance method were used for the assessment of patients' adherence to GH. The potential barriers to GH therapy adherence and medication persistence were also explored. Results: Based on the MMAS method, 56.7% of the children and 57.9% of the adolescent groups were adherent to GH therapy. Conversely, according to the auto-compliance method almost all the patients were adherent in the children (95.2%) and adolescent (95.5%) groups. Forgetting to take the injection or refill the prescription, being away from home, exhaustion from long-term injection, drug shortage and inaccessibility to the pharmacy were barriers found to be significantly associated with a low adherence in the children group. While in the adolescent group, forgetting to take the injection, painful injection, concern about longterm complications and exhaustion from long-term injection revealed a significant association with low adherence. Persistence with GH therapy was reported in 75.3% and 67% of children and adolescent patients, respectively.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The probable barriers to GH therapy adherence were assessed by a questionnaire, which was designed based on the reported results of the Rosenfeld et al study [23].…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Adherence to growth hormone therapy in children and its potential barriers

Mohseni

Heydari

Qorbani

et al. 2017

Journal of Pediatric Endocrinology and Metabolism

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“…For example, human growth hormone (hGH) is a 22-kDa four-helix-bundle protein produced by the pituitary gland, and its recombinant form has long been used for the treatment of growth hormone deficiency (GHD). Due to the short in vivo half-life of hGH, which is on the timescale of minutes, current GHD therapy requires daily injection (4), resulting in lower patient compliance (5). Studies have shown that a continuous infusion of recombinant (r)hGH has a similar efficacy and safety profile as daily rhGH therapy (6), and thus there is considerable interest in the development of long-acting forms of hGH.…”

mentioning

confidence: 99%

Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists

Liu

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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On the basis of the 3D structure of a bovine antibody with a wellfolded, ultralong complementarity-determining region (CDR), we have developed a versatile approach for generating human or humanized antibody agonists with excellent pharmacological properties. Using human growth hormone (hGH) and human leptin (hLeptin) as model proteins, we have demonstrated that functional human antibody CDR fusions can be efficiently engineered by grafting the native hormones into different CDRs of the humanized antibody Herceptin. The resulting Herceptin CDR fusion proteins were expressed in good yields in mammalian cells and retain comparable in vitro biological activity to the native hormones. Pharmacological studies in rodents indicated a 20-to 100-fold increase in plasma circulating half-life for these antibody agonists and significantly extended in vivo activities in the GH-deficient rat model and leptin-deficient obese mouse model for the hGH and hLeptin antibody fusions, respectively. These results illustrate the utility of antibody CDR fusions as a general and versatile strategy for generating long-acting protein therapeutics.antibody | protein engineering | growth hormone | leptin | pharmacology M any endocrine hormones are used therapeutically (1); however, they generally suffer from short circulating halflives (2, 3) and therefore require high doses and frequent injections to achieve efficacious exposures. For example, human growth hormone (hGH) is a 22-kDa four-helix-bundle protein produced by the pituitary gland, and its recombinant form has long been used for the treatment of growth hormone deficiency (GHD). Due to the short in vivo half-life of hGH, which is on the timescale of minutes, current GHD therapy requires daily injection (4), resulting in lower patient compliance (5). Studies have shown that a continuous infusion of recombinant (r)hGH has a similar efficacy and safety profile as daily rhGH therapy (6), and thus there is considerable interest in the development of long-acting forms of hGH. The first and only approved long-acting hGH, Nutropin Depot, a sustained-release formulation based on a biodegradable polymer, was withdrawn due to manufacturing difficulties. Various forms of long-acting GH have since been generated: those currently in clinical development include LB03002 (microparticle suspension), NNC126-0083 (PEGylation), NNC0195-0092 (reversible albumin-binding GH derivative), MOD-4023 (CTP modification), ACP-001 (prodrug strategy), Albutropin (albumin fusion), and VRS-317 (XTEN fusion), and have been extensively reviewed elsewhere (5). However, challenges associated with heterogeneity, stability, immunogenicity, toxicity, and/or compromised potency could potentially limit their clinical utility (3, 7-10).Another short-lived hormone in which there is considerable clinical interest is human leptin, a 16-kDa four-helix-bundle protein that plays a central role in the homeostasis of body weight. Recombinant leptin has been approved for the treatment of leptindeficient lipodystrophy patients (11), and ...

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Assessment of the Pharmacokinetics, Pharmacodynamics, and Safety of Single Doses of TV‐1106, a Long‐Acting Growth Hormone, in Healthy Japanese and Caucasian Subjects

Cohen‐Barak

Barkay

Rasamoelisolo

et al. 2016

Clinical Pharm in Drug Dev

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TV‐1106 is a human serum albumin genetically fused to recombinant human growth hormone, designed to provide a long‐acting alternative to daily growth hormone (GH) injections in patients with GH deficiency. This study investigated the pharmacokinetics, pharmacodynamics, and safety of single subcutaneous doses of TV‐1106 (7.5, 15, 50, and 100 mg) in Japanese (n = 44) and caucasian (n = 44) healthy subjects. TV‐1106 pharmacokinetics and pharmacodynamics were comparable in Japanese and caucasian populations. TV‐1106 demonstrated relatively slow absorption (median tmax, 10–30 hours) and a mean elimination half‐life of 26–36 hours. Apparent clearance and volume of distribution decreased with increasing TV‐1106 doses in both populations and appeared to increase more than dose proportionality across the tested doses. Insulin‐like growth factor‐1 (IGF‐1) and IGF binding protein‐3 (IGFBP‐3) increased in a dose‐related manner, with maximum responses observed at 33–96 and 42–109 hours, respectively. IGF‐1 and IGFBP‐3 returned to baseline values at 168 hours following 7.5 and 15 mg of TV‐1106, and 336 hours following 50 and 100 mg of TV‐1106. TV‐1106 appeared safe in both populations. There was no evidence of differences in pharmacokinetics, pharmacodynamics, or safety of TV‐1106 between Japanese and caucasian populations. The data also demonstrate long‐acting growth hormone properties of TV‐1106 and support its potential for once‐weekly dosing.

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Compliance and Persistence in Pediatric and Adult Patients Receiving Growth Hormone Therapy

Cited by 171 publications

References 19 publications

Adherence to growth hormone therapy in children and its potential barriers

Adherence to growth hormone therapy in children and its potential barriers

Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists

Assessment of the Pharmacokinetics, Pharmacodynamics, and Safety of Single Doses of TV‐1106, a Long‐Acting Growth Hormone, in Healthy Japanese and Caucasian Subjects

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