Risk factors for montelukast treatment failure in step-down therapy for controlled asthma.
BACKGROUND
Leukotriene receptor antagonists including montelukast are an option for step-down therapy for mild asthmatics controlled on low-dose inhaled corticosteroids (ICS). Because some patients fail montelukast step-down therapy, it would be helpful for clinicians to be able to predict the risk of treatment failure.


OBJECTIVE
To determine patient characteristics associated with montelukast treatment failure and develop a clinical index to predict the risk of montelukast treatment failure.


METHODS
Using the 165 participants in the Leukotriene or Corticosteroid or Corticosteroid-Salmeterol Study (LOCCS) trial who were stepped down from low-dose ICS to montelukast, we determined associations between enrollment variables and treatment failure. We constructed a montelukast failure index to predict the risk of montelukast treatment failure during step-down. To assess its specificity for montelukast, index performance was evaluated in the other LOCCS treatment groups.


RESULTS
Characteristics independently associated with montelukast treatment failure included age of asthma onset <10 years old (OR = 2.39; 95% CI = 1.17-5.02; p = .018), need for steroid burst in the last year (OR = 2.39; 95% CI = 1.13-5.09; p = .022), and pre-bronchodilator forced expiratory volume in 1 s (FEV(1)) (OR = 1.44 per 10% lower % predicted; 95% CI = 1.07-1.97; p = .016). A montelukast failure index was generated from these three variables (range: -5 to 7 points). Scores <0 predicted low risk (<0.20) of treatment failure, whereas scores >5 predicted high risk (>0.60) of treatment failure.


CONCLUSIONS
Early asthma onset, worse asthma control in the last year, and lower pre-bronchodilator FEV(1) are associated with montelukast treatment failure. A montelukast failure index is proposed to quantify the risk of failure prior to treatment initiation.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. mdrummo3@jhmi.edu
M Bradley
MB
Drummond
Stephen P
SP
Peters
Mario
M
Castro
Janet T
JT
Holbrook
Charles G
CG
Irvin
Lewis J
LJ
Smith
Robert A
RA
Wise
Elizabeth A
EA
Sugar
D000085:Acetates / Q000627:therapeutic use*; D000280:Administration, Inhalation; D017668:Age of Onset; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D003521:Cyclopropanes; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D016015:Logistic Models; D011804:Quinolines / Q000627:therapeutic use*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013440:Sulfides; D017211:Treatment Failure
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D005938:Glucocorticoids; D011804:Quinolines; D013440:Sulfides; C093875:montelukast