Published online February 1, 2006
PEDIATRICS
Vol. 117
No. 2
February 2006, pp.
590-591
(doi:10.1542/peds.2005-2866)
"Inferiority Complex" for a Reason: In Reply
María L. García García, MD
Hospital Severo Ochoa Leganes,
28010 Madrid, Spain
In Reply.—
The Montelukast Study of Asthma in Children (MOSAIC) clinical trial1 is one of the first long-term (12 months of treatment) and large (n = 994) studies comparing the relative benefit of an oral leukotriene-receptor antagonist (montelukast) and an inhaled corticosteroid (fluticasone) in asthma control in children. This was a noninferiority study of children with mild persistent asthma, with the percent asthma rescue-free days (RFDs) as the primary end point. This end point measures any day during which the patient did not use asthma rescue medication (such as an inhaled ß-agonist or an oral corticosteroid) and did not have an unscheduled visit to a physician, urgent/ emergency care, or hospitalization. This composite end point is a simple yet informative measure of the status of the disease, assessing outcomes of relevance to the patient, as previously emphasized.2 Furthermore, such inclusive end points may have advantages over "traditional" assessments of asthma control such as lung measures, given their frequent lack of reproducibility in young children and their lack of correlation with symptoms.
The results of the study showed that the mean difference in percent RFDs between the 2 treatments was 2.8% (<1 day/month), an outcome that should not be clinically significant to patients. This result, of course, meets an essential condition of comparability of treatments in a noninferiority trial, namely, that the difference between treatments be clinically nonimportant. However, several secondary end points favored fluticasone.
The overlap in response distributions can often provide a clearer determination of clinical comparability because the entire range of response of individuals in the study population is taken into account, which conveys to physicians a better understanding of the range of expectations for patient outcomes. In a posthoc, nonparametric analysis of the primary end point, there was a large degree of overlap (84.3% [95% confidence interval: 77.0–91.6]) in the response of patients who were treated with either active therapy.
This was a randomized, double-blind study in which the baseline asthma characteristics between the 2 treatment groups were very similar. The growth results need to be confirmed further under additional controlled conditions, including Tanner stage of maturation. Along these lines, a recent 1-year, randomized, double-blind, placebo-controlled study of prepubertal children with mild persistent asthma showed that montelukast, in contrast to beclomethasone, did not affect linear growth.3
The management of asthma in children poses challenges that differ from the treatment of asthma in adults. Current guidelines are inadequate: a case in point is the grouping of children >5 years old as adults in treatment recommendations and the lack of age-specific guidelines for children who are <5 years of age.4 Improved guidelines are needed that encourage physicians to consider several therapeutic options for an optimal control of symptoms during the course of their long-term management of the child's disease, taking into account issues of not just efficacy but also adherence, ease of use, and safety.
REFERENCES
- García García ML, Wahn U, Gilles L, Swern A, Tozzi CA, Polos P. Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: the MOSAIC study.
Pediatrics. 2005;116
:360
–369[Abstract/Free Full Text]
- Garcia ML. Evaluating asthma control with montelukast in children with mild asthma in the MOSAIC study.
Pediatrics. 2005;116(2)
. Available at: www.pediatrics.org/cgi/eletters/116/2/493
- Knorr BA, Kuznetsova O, Reiss TF, et al. Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week, randomized, double-blind study.
J Allergy Clin Immunol. 2005;115
(2 suppl):S148–S148
- National Institutes of Health, National Heart, Lung, and Blood Institute.
Global Strategy for Asthma Management and Prevention. Bethesda, MD: National Institutes of Health; 1995. NIH Publication 02-3659
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
