Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week randomized double-blind study

doi:10.1016/S1081-1206(10)61342-7

Annals of Allergy, Asthma & Immunology

Volume 96, Issue 6, June 2006, Pages 800-807

https://doi.org/10.1016/S1081-1206(10)61342-7 Get rights and content

Background

Antileukotrienes and inhaled corticosteroids are asthma controller agents widely used in the treatment of pediatric asthma.

Objective

To evaluate the effects of montelukast and beclomethasone on linear growth in prepubertal asthmatic children for 1 year.

Methods

This was a 30-center study of boys (6.4-9.4 years old) and girls (6.4-8.4 years old) at Tanner stage I with mild, persistent asthma. After a placebo run-in period, 360 patients were randomized in equal ratios to double-blind, double-dummy treatment with 5 mg of montelukast, 200 μg of beclomethasone twice daily (positive control), or placebo for 56 weeks; 90% of the patients completed the study. The primary end point was linear growth velocity, measured using a stadiometer.

Results

Linear growth rates were similar between the montelukast and placebo groups; the mean difference for the year was 0.03 cm. The mean growth rate with beclomethasone was significantly less than with placebo (−0.78 cm) or montelukast (0.81 cm) (P < .001 for both). Median percentage of days with β-agonist use was greater with placebo (14.58%) vs montelukast (10.55%) or beclomethasone (6.65%) (P < .05 for all). More patients used oral corticosteroid rescue with placebo (34.7%) than with montelukast (25.0%) or beclomethasone (23.5%). An imbalance in bone marker levels was seen with beclomethasone but not with montelukast.

Conclusion

In prepubertal asthmatic children, montelukast did not affect linear growth, whereas the growth rate with beclomethasone was significantly decreased during 1 year of treatment.

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Citation Excerpt :
Even though approved and widely used for children in other countries, the FDA did not approve ciclesonide for use in children younger than 12 years of age. In another well-designed controlled clinical trial, children with mild persistent asthma treated with montelukast and placebo for 1 year grew normally, but children treated with the ICS beclomethasone grew 1 cm less.21 A larger trial conducted in 5- to 12-year-old children with mild-moderate persistent asthma (Childhood Asthma Management Program [CAMP] trial) showed that 5 years of treatment with an FDA-approved, low-dose ICS budesonide also caused a similar negative effect on growth (∼1 cm).21
All drugs have potential side effects, but thoughtful use can maximize benefits while minimizing risks. Children should not be considered just small adults regarding drug safety because their growth and development are discordant with their ability to sense and self-report drug side effects. Detecting side effects requires vigilance and education from prescribers to parents, who are tasked with monitoring their child over time. A drug’s safety profile is published in the package label after pivotal trials are conducted in relatively small and sometimes narrow segments of the population during the U.S. Food and Drug Administration approval process. Drug safety profiles can change as data from postmarketing reports and long-term monitoring during phase IV trials emerge. As such, prescribers are obligated to maintain current understanding of any changes to drug labels. Discussing potential side effects, monitoring, and when to report concerns can be a time-consuming process during patient encounters. This review offers current information regarding potential side effects of some of the most commonly used medications for allergic conditions, asthma, and atopic dermatitis. This information and discussion will hopefully assist clinicians in their conversations with parents, including advice surrounding prescribing medication to minimize adverse effects, parental monitoring, and documentation.
The safety of long-term use of inhaled corticosteroids in patients with asthma: A systematic review and meta-analysis
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The P value of Begg's rank correlation test (STATA 12.0) was used to assess the presence of publication bias in included articles for each outcome. Of 17,234 trials recognized by the initial search, 331 were retrieved for more detailed assessment, and 86 trials [8–91,105–107] were included in the meta-analysis (Fig. 1). Baseline characteristics of trials included in the meta-analysis are shown in Table 1.
This systematic review and meta-analysis was performed to determine the safety of long-term use of ICS in patients with asthma.
A systematic search was made of PubMed, Embase, Web of Science, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of asthma with ICS, compared with non-ICS treatment (placebo or other active drugs), were reviewed.
Eighty-six RCTs (enrolling 51,538 participants) met the inclusion criteria. Oral or oropharyngeal candidiasis (RR 2.58, 95% CI 2.00 to 3.33), and dysphonia/hoarseness (RR 1.56, 95% CI 1.31 to 1.85) were less frequent in the control group. There was no statistically significant difference in the risk of upper respiratory tract infection, lower respiratory tract infection, influenza, decline in bone mineral density, and fractures between the two groups.
In addition to the mild local adverse events, the long-term use of ICS was safe in patients with asthma.
Inhaled corticosteroids: Effects on growth and bone health
2016, Annals of Allergy, Asthma and Immunology
Both slowed growth in children and reduced bone mineral density (BMD) are systemic effects of corticosteroids, and there is concern about the degree to which these systemic effects affect growth and BMD.
To engage in a data-driven discussion of the effects of inhaled corticosteroids (ICSs) on growth in children and BMD.
Articles were selected based on their relevance to this review.
Studies of ICSs in children in which growth was a secondary outcome have revealed slowed growth associated with low doses of budesonide, fluticasone propionate, and beclomethasone dipropionate. In the study of budesonide, the effect was permanent, and in the study of fluticasone propionate, the effect was long-lasting, but it is unclear whether the effect was permanent. However, the results of studies in which growth was the primary outcome were mixed. Slowed growth was detected in a study of beclomethasone dipropionate; however, slowed growth was not detected in a study of ciclesonide or flunisolide. A decrease in BMD acquisition in children was associated with high doses but not low to medium doses of ICSs. In adults, there was a dose-related effect of ICSs on BMD. Both higher daily dose and larger cumulative dose were associated with increased bone density loss.
Because of the systemic effects on growth and bone health, children should be monitored for growth using stadiometry every 3 to 6 months and BMD should be monitored yearly in patients being treated with high doses of ICSs.
Risk of Adverse Effects, Misdiagnosis, and Suboptimal Patient Care with the Use of Over-the-Counter Triamcinolone
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Montelukast in the treatment of mild to moderate persistent asthma
2011, Revue des Maladies Respiratoires
Un anti-inflammatoire est recommandé en cas d’asthme persistant. Si les corticoïdes inhalés (CI) restent la référence, des alternatives sont préconisées. Parmi celles-ci, l’antagoniste des récepteurs aux leucotriènes (montelukast) est proposé en monothérapie ou en association aux CI.
En monothérapie, il est efficace pour contrôler l’asthme d’effort. Dans un contexte d’asthme persistant léger, montelukast est aussi efficace qu’un CI à faible dose. Associé à un CI, montelukast est aussi efficace que les CI à double posologie pour contrôler un asthme persistant modéré.
Son efficacité clinique, sa bonne tolérance et son observance excellente permettent de valider montelukast, pour le traitement des asthmes persistants légers à modérés, de l’adulte et de l’enfant, en alternative ou en association aux CI.
Anti-inflammatory preventive treatment is recommended in cases of persistent asthma. Besides inhaled corticosteroids (ICS), which represent the mainstay of treatment, other therapeutic options are available, of which only antileukotrienes are approved for all age groups.
Given as a substitute of low-dose ICS, montelukast prevents exacerbations as efficiently and for a longer period than long-acting β2-agonists. Montelukast is as efficient as doubling the dose of ICS on asthma symptoms in cases of inadequate control with low-dose ICS. Combined with ICS, it can lead to better control of asthma and potentially to ICS sparing.
Given the efficacy, tolerance and long-term treatment compliance of montelukast in mild persistent asthma in adults and children, montelukast, given as a substitute or combined with ICS, could contribute to enhanced control of asthma, especially in children.
Adherence to inhaled corticosteroids: Comparison of available therapies
2010, Pulmonary Pharmacology and Therapeutics
Adherence to daily anti-inflammatory therapy, the cornerstone being inhaled corticosteroids (ICSs), is critical for the control of persistent asthma. Many factors, both behavioral and treatment-related, can affect treatment adherence. In the pediatric population, adherence is often the responsibility of parents/caregivers. Thus, parents may need improved awareness of the major asthma controller medications, especially regarding the efficacy and safety of ICSs; their beliefs or concerns regarding asthma therapy have a bearing on their diligence in encouraging adherence with the prescribed treatment regimen. Dosing complexity and factors relating to inhaler use are also important components of adherence. There are currently 6 ICSs (excluding nebulized ICSs) approved for children in the United States. The purpose of this review is to examine and compare the features of the available ICSs that may influence adherence in the treatment of pediatric asthma.

View all citing articles on Scopus

: This study was supported by a research grant from Merck Research Laboratories, Rahway, NJ.

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ORIGINAL ARTICLESLinear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week randomized double-blind study

Background

Objective

Methods

Results

Conclusion

J Allergy Clin Immunol

Lancet

J Pediatr

J Pediatr

J Pediatr

J Allergy Clin Immunol

Childhood asthma

Curr Allergy Asthma Rep

The effect of asthma and its treatment on growth

Arch Dis Child

Effect of long-term treatment with inhaled budesonide on adult height in children with asthma

N Engl J Med

The effect of inhaled steroids on the linear growth of children with asthma: a meta-analysis

Pediatrics

Low-dose inhaled budesonide once or twice daily for 27 months in children with mild asthma

Allergy

Montelukast, a leuko-triene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years

Pediatrics

Use of oral montelukast in the treatment of asthma

Compr Ther

ORIGINAL ARTICLES
Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week randomized double-blind study