Recombinant growth hormone therapy for cystic fibrosis in children and young adults

TY - JOUR

T1 - Recombinant growth hormone therapy for cystic fibrosis in children and young adults

AU - Thaker, Vidhu

AU - Carter, Ben

AU - Putman, Melissa

N1 - Funding Information: The study was supported by a grant from the Mukoviszidose e.V Foundation. Pharmacia GmbH provided the Genotropin®. Funding Information: Although all effort was made to search for unpublished data, it is possible that unpublished trials with unfavourable results may not have been identified in the search, which could potentially alter the results of the review. Three of the included trials were funded in part by industry-sponsored grants. We were unable to contact the authors of the trials to understand the process of funding and whether industry support was limited to the supply of the medication or extended to statistical and analysis support. We were also unable to contact authors of unpublished trials listed in the database http://clinical trials.gov. Funding Information: "Supported in part by the Genentech Center for Clinical Research". Funding Information: "The study was supported by a grant from the Genetech Center for Clinical Research in Endocrinology." The first author previously served on the advisory board for Genentech. Funding Information: Partially supported by a grant from Genentech Foundation, the manufacturer of rhGH used in the trial. Funding Information: The authors would like to thank Nikki Jahnke of the Cochrane Cystic Fibrosis and Genetic Disorders Group for her support throughout the development of this review. Thanks to Dr. Alexandra Haagensen, Zbys Fedorowicz and Brian Houston for contributions to the prior versions of this review. We also acknowledge Tahereh Ziafazeli and Amir Nekouei for translating a paper written in Persian. This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health. Funding Information: This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health. Publisher Copyright: Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

PY - 2021/8/23

Y1 - 2021/8/23

N2 - Background: Cystic fibrosis (CF) is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with CF often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant human growth hormone (rhGH), has been proposed as a potential intervention. This is an update of a previously published review. Objectives: To evaluate the effectiveness and safety of rhGH therapy in improving lung function, quality of life and clinical status of children and young adults with CF. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 12 January 2021. We also searched ongoing trials registers:. clinicaltrials.gov from the United States - date of latest search 19 Jun 2021;
WHO International Clinical Trials Registry Platform (ICTRP) - date of latest search 05 March 2018 (not available in 2021). We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Web of Science, Scopus and Proceedings First. Date of latest search: 21 Jun 2021. Selection criteria: Randomised and quasi-randomised controlled trials of all preparations of rhGH compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults (aged up to 25 years) diagnosed with CF (by sweat test or genetic testing). Data collection and analysis: Two authors independently screened papers, extracted trial details and assessed their risk of bias. We assessed the quality of the evidence using the GRADE system. Main results: We included eight trials (291 participants, aged between five and 23 years) in the current version of the review. Seven trials compared standard-dose rhGH (approximately 0.3 mg/kg/week) to no treatment and one three-arm trial (63 participants) compared placebo, standard-dose rhGH (0.3 mg/kg/week) and high-dose rhGH (0.5 mg/kg/week). Six trials lasted for one year and two trials for six months. We found that rhGH treatment may improve some of the pulmonary function outcomes, but there was no difference between standard and high-dose levels (low-certainty evidence, limited by inconsistency across the trials, small number of participants and short duration of therapy). The trials show evidence of improvement in the anthropometric parameters (height, weight and lean body mass) with rhGH therapy, again no differences between dose levels. We found improvement in height for all comparisons (very low- to low-certainty evidence), but improvements in weight and lean body mass were only reported for standard-dose rhGH versus no treatment (very low-certainty evidence). There is some evidence indicating a change in the level of fasting blood glucose with rhGH therapy, however, it did not cross the clinical threshold for diagnosis of diabetes in the trials of short duration (low-certainty evidence). There is low- to very low-certainty evidence for improvement of pulmonary exacerbations with no further significant adverse effects, but this is limited by the short duration of trials and the small number of participants. One small trial provided inconsistent evidence on improvement in quality of life (very low-certainty evidence). There is limited evidence from three trials in improvements in exercise capacity (low-certainty evidence). None of the trials have systematically compared the expense of therapy on overall healthcare costs. Authors' conclusions: When compared with no treatment, rhGH therapy is effective in improving the intermediate outcomes in height, weight and lean body mass. Some measures of pulmonary function showed moderate improvement, but no consistent benefit was seen across all trials. The significant change in blood glucose levels, although not causing diabetes, emphasizes the need for careful monitoring of this adverse effect with therapy in a population predisposed to CF-related diabetes. No significant changes in quality of life, clinical status or side-effects were observed in this review due to the small number of participants. Long-term, well-designed randomised controlled trials of rhGH in individuals with CF are required prior to routine clinical use of rhGH in CF.

AB - Background: Cystic fibrosis (CF) is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with CF often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant human growth hormone (rhGH), has been proposed as a potential intervention. This is an update of a previously published review. Objectives: To evaluate the effectiveness and safety of rhGH therapy in improving lung function, quality of life and clinical status of children and young adults with CF. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 12 January 2021. We also searched ongoing trials registers:. clinicaltrials.gov from the United States - date of latest search 19 Jun 2021;
WHO International Clinical Trials Registry Platform (ICTRP) - date of latest search 05 March 2018 (not available in 2021). We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Web of Science, Scopus and Proceedings First. Date of latest search: 21 Jun 2021. Selection criteria: Randomised and quasi-randomised controlled trials of all preparations of rhGH compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults (aged up to 25 years) diagnosed with CF (by sweat test or genetic testing). Data collection and analysis: Two authors independently screened papers, extracted trial details and assessed their risk of bias. We assessed the quality of the evidence using the GRADE system. Main results: We included eight trials (291 participants, aged between five and 23 years) in the current version of the review. Seven trials compared standard-dose rhGH (approximately 0.3 mg/kg/week) to no treatment and one three-arm trial (63 participants) compared placebo, standard-dose rhGH (0.3 mg/kg/week) and high-dose rhGH (0.5 mg/kg/week). Six trials lasted for one year and two trials for six months. We found that rhGH treatment may improve some of the pulmonary function outcomes, but there was no difference between standard and high-dose levels (low-certainty evidence, limited by inconsistency across the trials, small number of participants and short duration of therapy). The trials show evidence of improvement in the anthropometric parameters (height, weight and lean body mass) with rhGH therapy, again no differences between dose levels. We found improvement in height for all comparisons (very low- to low-certainty evidence), but improvements in weight and lean body mass were only reported for standard-dose rhGH versus no treatment (very low-certainty evidence). There is some evidence indicating a change in the level of fasting blood glucose with rhGH therapy, however, it did not cross the clinical threshold for diagnosis of diabetes in the trials of short duration (low-certainty evidence). There is low- to very low-certainty evidence for improvement of pulmonary exacerbations with no further significant adverse effects, but this is limited by the short duration of trials and the small number of participants. One small trial provided inconsistent evidence on improvement in quality of life (very low-certainty evidence). There is limited evidence from three trials in improvements in exercise capacity (low-certainty evidence). None of the trials have systematically compared the expense of therapy on overall healthcare costs. Authors' conclusions: When compared with no treatment, rhGH therapy is effective in improving the intermediate outcomes in height, weight and lean body mass. Some measures of pulmonary function showed moderate improvement, but no consistent benefit was seen across all trials. The significant change in blood glucose levels, although not causing diabetes, emphasizes the need for careful monitoring of this adverse effect with therapy in a population predisposed to CF-related diabetes. No significant changes in quality of life, clinical status or side-effects were observed in this review due to the small number of participants. Long-term, well-designed randomised controlled trials of rhGH in individuals with CF are required prior to routine clinical use of rhGH in CF.

UR - http://www.scopus.com/inward/record.url?scp=85114848542&partnerID=8YFLogxK

U2 - 10.1002/14651858.CD008901.pub5

DO - 10.1002/14651858.CD008901.pub5

M3 - Article

C2 - 34424546

AN - SCOPUS:85114848542

SN - 1465-1858

VL - 2021

JO - Cochrane Database of Systematic Reviews

JF - Cochrane Database of Systematic Reviews

IS - 8

M1 - CD008901

ER -