Longitudinal growth in infants and young children treated with budesonide inhalation suspension for persistent asthma,☆☆,

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Abstract

Background: Results of recent growth studies suggest that inhaled glucocorticosteroids may affect growth in children. Objective: Three 52-week, open-label extension studies (studies A, B, and C) were conducted to compare the effects of budesonide inhalation suspension (BIS) with conventional asthma therapy (CAT) on long-term safety, including intermediate-term growth, in 3 different pediatric asthma populations. Methods: Pediatric asthma patients (ages 6 months to 8 years) from 3 multicenter, randomized, 12-week, double-blind, placebo-controlled studies were eligible to enroll in the 52-week, open-label extension studies. The extension studies were multicenter, randomized, open-label, active-controlled, parallel-group studies performed at 26 centers in the United States. Subjects in each extension study were randomized in a 2:1 ratio to receive either BIS or CAT. BIS was initially administered at a dose of 0.5 mg once (studies A and C) or twice daily (study B), with attempts made at each clinical visit to gradually reduce the dose to the minimum effective dose that maintains asthma control, as judged by the investigator. CAT consisted of any available therapy for asthma, including inhaled glucocorticosteroids in studies B and C only. Height SD scores, growth velocity, and skeletal age (only in studies B and C) were examined. Results: In total, 670 subjects were randomized; 223 subjects received CAT and 447 received BIS. Mean ages at entry were 63.0 months and 60.9 months in CAT and BIS groups, respectively. Median total daily doses of BIS ranged from 0.5 to 1.0 mg and the mean duration of treatment exposure was 304 ± 119 days and 342 ± 83 days in CAT and BIS groups, respectively. Changes in height SD scores differed significantly between the BIS and CAT groups in study A (–0.19, P = .003), and there was a small, statistically significant decrease in growth velocity (–0.8 cm/y, P = .002) in the BIS-treated group compared with the CAT group. No significant differences were observed between BIS and CAT groups in the changes in height SD scores or in growth velocities in studies B (+0.10 and +0.7 cm/y, respectively) and C (+0.12 and +0.8 cm/y, respectively). No differences in skeletal age were observed between BIS and CAT groups in studies B and C. Conclusion: There was a small, statistically significant decrease in growth velocity in the BIS-treated group compared with the CAT group in the study (study A) where inhaled glucocorticosteroid use was prohibited before entry and in the CAT group during the study. In the studies (B and C) where inhaled glucocorticosteroids were allowed in the CAT group, no differences were observed in height SD scores or growth velocity. The clinical relevance of these effects, including impact on final adult height, remain to be determined in prospectively planned studies that assess growth in children. (J Allergy Clin Immunol 2000;105:259-68.)

Section snippets

Subjects

Boys and girls (aged 6 months to 8 years) with persistent asthma from 3 multicenter, randomized, 12-week, double-blind, placebo-controlled studies were eligible to enroll in three 52-week open-label extension studies. Details of the inclusion/exclusion criteria and findings for the 12-week studies are reported elsewhere.2, 16, 17 In general, subjects were included in each of the 52-week extension studies if they completed one of the 12-week, double-blind studies or were discontinued from

Subjects

In total, 670 subjects were evaluable in the 52-week studies; of these, 223 subjects received CAT and 447 received BIS. Subject demographics and baseline asthma characteristics for each of the studies are shown in Tables I and II, respectively. Overall and within each study, sex and race distributions were comparable between the CAT and BIS groups (Table I). Children in study B were older (aged 4 to 9 years) and hence taller than children in studies A (aged 8 months to 9 years) and C (aged 1

DISCUSSION

The effects of inhaled GCSs on growth in children have been at the forefront of pediatric asthma treatment issues since the US Food and Drug Administration (FDA) convened a joint meeting of the Pulmonary Allergy and the Metabolic Endocrinologic Drug Advisory Committees in July 1998. In the current study the effects of BIS on growth were assessed in 3 different populations of children with asthma who therefore had different treatment needs: study A included children with mild persistent asthma

Acknowledgements

We thank Betty Angelini, RN, BSN, and Nancy Bormann, PhD, for their thoughtful review of this manuscript.

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    Supported by AstraZeneca LP.

    ☆☆

    Reprint requests: David P. Skoner, MD, Division of Allergy, Immunology, and Infectious Diseases, Children’s Hospital of Pittsburgh, Department of Pediatrics, 3705 Fifth Ave at DeSoto, Pittsburgh, PA 15213-2583.

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