PURPOSE:Montelukast (MNT), an antileukotriene, and loratadine (LRT), an antihistamine, have shown additive effects against bronchoconstriction in antigen-challenge models. This study investigated the additive effects of concomitant MNT and LRT compared to MNT, LRT and inhaled beclomethasone (BEC) monotherapies in clinical asthma.
METHODS:Patients (n=406) were 15–65 years old with an FEV1 predicted of 50–85%, FEV1 reversibility ≥15% after short-acting β-agonist, and a minimal level of daytime symptoms and β-agonist use. This 2 X 2 crossover study consisted of two double-blind 6-week treatment periods where patients were administered once daily oral MNT 10 mg, oral LRT 10 mg, oral MNT 10 mg+LRT 10 mg, or twice daily inhaled BEC 200 μg. Patients from the study were then enrolled into an open-label 48-week extension study comparing MNT+LRT and BEC. The primary endpoint was the percent change from baseline in FEV1.
RESULTS:Over 6 weeks of double-blind treatment, significant improvements (p<0.05) in FEV1 were seen for MNT+LRT vs LRT (least-square mean percentage-point difference of 5.8%), BEC vs MNT+LRT (2.35%), MNT vs LRT (5.94%), and BEC vs MNT (4.65%); a numerical improvement (p=0.054) was seen for MNT+LRT vs MNT (1.60%). In secondary endpoint results, significant improvements for MNT+LRT vs MNT were seen in some (Evening peak expiratory flow, Nocturnal asthma symptom score, Nocturnal awakenings, and Asthma-specific quality-of-life) but not other endpoints. No improvement of MNT+LRT vs BEC was seen in any endpoint. Significant improvements in all endpoints except Daytime asthma symptoms score and Peripheral blood eosinophil counts were seen for MNT+LRT vs LRT. In the extension study, both MNT+LRT and BEC improved several endpoints. All treatments were generally comparable in the percent of patients with clinical and laboratory adverse experiences.
CONCLUSION:In this study, loratadine added to montelukast did not demonstrate consistent additional benefits in endpoints of asthma control.
CLINICAL IMPLICATIONS:Loratadine did not provide clinically important additive benefits to montelukast alone in this study.
DISCLOSURE:Susan Lu, University grant monies None; Grant monies (from sources other than industry) None; Grant monies (from industry related sources) None; Shareholder Authors Reiss, Lu, and Liu may own stock or hold stock options in the company Merck & Co., Inc.; Employee Authors Reiss, Lu, and Liu are employees of Merck Research Laboratories, Merck & Co. Inc.; Fiduciary position (of any organization, association, society, etc, other than ACCP None; Consultant fee, speaker bureau, advisory committee, etc. None; Other None; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Concomitant administration of montelukast and loratadine