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No Long-Term Effects on Growth in Asthmatic Children Using Floventle

Question

  • You start a 6 year old girl on Flovent and her parents read that this could potentially affect her growth.  Does Flovent have long-term effects on growth in children with persistent asthma?

Clinical Bottom Lines

  1. Long-term administration (1 year) of inhaled fluticasone propionate (100 micrograms and 200 micrograms/day) is well-tolerated in children with persistent asthma.1
  2. No statistically significant differences were noted between fluticasone propionate and placebo treatment groups with respect to height measurement, growth velocity, or skeletal age.
  3. An overall difference of 0.42 cm/yr in mean change from baseline in height between patients treated with fluticasone propionate 100 micrograms and those treated with placebo could be attributable to a small drug effect or withdrawal of poorly controlled, slower growing children from the placebo group because of worsening asthma control.
  4. It remains appropriate to use the minimum effective dose of inhaled corticosteroid in children and to monitor growth of children by using stadiometry during treatment, particularly at higher doses.


Summary of Key Evidence

  1. In a double-blind, randomized, parallel-group, multicenter study, 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder (50 or 100 micrograms) administered twice daily by a breath-actuated device for 1 year.
  2. Growth was evaluated monthly; other safety variables and pulmonary function were evaluated periodically.
  3. Children eligible for the study had normal growth rates as defined by height measurements (one measurement taken 6 to 18 months before the study and one at screening) between the 5th and 95th percentiles and growth velocity between the 10th and 97th percentiles.
  4. The mean height increases from baseline to 52 weeks were 6.15 +/- 0.17 cm, 5.94 +/- 0.16 cm and 5.73 +/- 0.13 cm in patients treated with twice daily doses of placebo, fluticasone propionate 50 micrograms, and fluticasone propionate 100 micrograms, respectively (p=0.308 overall). At the end of the treatment, corresponding values for mean growth velocity were 6.10 +/- 0/17, 5.91 +/- 0.16, and 5.67 +/- 0.13 cm/year with placebo, fluticasone propionate 50 micrograms and 100 micrograms, respectively (p=0.313, overall).  Corresponding values for mean change from baseline in growth velocity were -0.11 +/- 0.15,  -0.40 +/- 0.20, -0.46 +/- 0.15 cm/year, respectively (p=0.380, overall).
  5. Changes in height at the end of treatment were comparable to normal growth rates for patients of similar age.
  6. Skeletal maturation at baseline was comparable to chronologic age at baseline for all treatment groups.  At the end of 1 year of treatment, the mean change from baseline in skeletal age was 1.13 +/- 0.06 years, 1.13 +/1 0.06 years, and 0.95 +/- 0.05 years in patients treated with twice daily doses of placebo, fluticasone propionate 50 micrograms, and fluticasone propionate 100 micrograms, respectively (p=0.146, overall).
  7. The target enrollment size of 90 patients per treatment group was chosen to provide 80% power of detecting a 1.0 cm per year difference in height velocity between treatment groups.
  8. Only 66% of prepubescent patients in the placebo group completed the 52-seek treatment period compared with more than 80% of patients in each of the two treatment groups.
  9. No significant difference were noted among treatment groups with respect to drug-related adverse events, clinical laboratory tests, and ophthalmologic examinations.

Additional Comments

  • All patients remaining in the study were prepubescent as defined by a sexual maturity rating of 1 in any Tanner classification.
  • Of the 268 prepubescent patients remaining in the study, similar clinical characteristics at baseline existed across treatment groups.
  • Patients had a history of persistent asthma for at least 3 months--patients were required to have an FEV1 of at least 60% of predicted.
  • Patients were excluded if they had received systemic, intranasal, or ophthalmic corticosteroids within the month before study entry or had cataracts, glaucoma, or any other significant concurrent disease or condition.  Previous systemic corticosteroid use was limited to a total of 60 days within the 2 years before study entry.
  • Patients on a maintenance dose of inhaled corticosteroids were required to maintain a fixed dosage regimen for at least 3 months before screening.  Patients not on a fixed regimen were not allowed to use inhaled corticosteroid for more than 60 days within 2 years before screening.
  • The data presented in the current study are consistent with those of other studies in which growth was not impaired in children who were treated for at least 1 year with inhaled budesonide (Pulmicort) 200 or 400 micrograms/day or with beclomethasone dipropionate (Vanceril/Beclovent) 300 micrograms/day--"medium potency."
  • Growth was suppressed in children who received beclomethasone dipropionate 400 micrograms/day for 7 months, 400 micrograms/day for 1 year, or 200 micrograms/day to 800 micrograms/day for up to 6 years.  However, these three studies have been criticized for short duration, lack of assessment of pubertal status, lack of an untreated control group, lack of  baseline growth velocity measurements, use of chronologic age versus bone age assessments, and differences between treatment groups in baseline heights and ages.
  • The design of this study represents the first of its kind to address multiple confounding factors that weakened the results of previous growth studies

Citation

  1. Allen DB, Bronsky EA, LaForce CF, et al.  Growth in asthmatic children treated with fluticasone propionate.  Journal of Pediatrics 1998;132 (3):  472-7.


CAT Author: Bethany Mohr, MD

CAT Appraisers: John Frohna, MD

Date appraised: October 11, 1999

Last updated June 15, 2003
Department of Pediatrics and Communicable Diseases
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