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. Objectives. 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. Conclusion. 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.