The use of recombinant growth hormone to improve growth and health in children and young adults with cystic fibrosis

Review question

We reviewed the evidence about the effects of recombinant human growth hormone (rhGH) on the health of people with cystic fibrosis (CF).

Background

CF is an inherited condition causing disease in the lungs, digestive system and pancreas. People with CF are often underweight and have delayed growth, that may impact their lung function. Nutritional supplements may not be enough and it has been suggested that treatment with rhGH, which improves the rate of growth and bone density, might help. Treatment with rhGH is usually given once a day via a needle under the skin. It is expensive and may affect glucose metabolism that has implications for children at risk of CF-related diabetes. Hence, we need to critically review the risks and benefits of this treatment. This is an update of an earlier review.

Search date

The evidence is current to: 22 October 2018.

Study characteristics

This review looked at using of rhGH to improve lung function, growth and quality of life for children and young adults with CF. It includes eight trials with 291 individuals with CF being selected for one treatment or the other randomly. The individuals in the trials were five to 23 years old, but most had not yet reached puberty. Six trials lasted for one year and two trials for six months. Treatment with rhGH was compared to no treatment in seven trials and to a placebo (a liquid that did not contain any growth hormone) in one trial. The trial that used a placebo compared it to two different doses of rhGH treatment.

Key results

Results showed a modest improvement in height, weight and lean body mass between six and 12 months. However, there was no consistent evidence that rhGH treatment improves lung function, muscle strength, or quality of life. The trials were small and we did not find any evidence on changes in glucose metabolism or the long-term risk of diabetes due to the treatment. Given these results, we are not able to identify any clear benefit of therapy and believe that more research from well-designed, adequately powered clinical trials is needed.

Quality of the evidence

We did not have enough information to decide if overall the trials were biased in a way that might affect the results. All the measured outcomes were clearly reported in the trials, but the trials were small, and did not have enough participants to show a difference that may not have been due to chance. We also had concerns that outcomes which were based on personal judgement, such as quality of life scores, might be affected because those taking part in seven of the trials were able to tell which group they were in.

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.

Read the full abstract...
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 strategy: 

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: 22 October 2018.

We also searched ongoing trials registers in clinicaltrials.gov from the United States and WHO International Clinical Trials Registry Platform (ICTRP). Date of latest search: 05 March 2018.

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: 04 March 2018.

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 this revision 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-quality 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 quality evidence), but improvements in weight and lean body mass were only reported for standard-dose rhGH versus no treatment (very low-quality 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-quality evidence). There is low- to very low-quality 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-quality evidence). There is limited evidence from three trials in improvements in exercise capacity (low-quality evidence). None of the trials have systematically compared the expense of therapy on overall healthcare costs.

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