Clinical Observation of Montelukast as a Partner Agent for Complementary Therapy

Study Objectives To compare the clinical benefits of adding montelukast to inhaled budesonide with doubling the dose of inhaled budesonide in adult patients who were symptomatic on inhaled budesonide alone Price DB et al Thorax 2003;58:

Patients aged between 15 and 75 years Diagnosed with asthma for >1 year Asthma not optimally controlled (as judged by investigator) Regular use of inhaled corticosteroids Baseline FEV 1 value  50% predicted Beta-agonist reversibility in FEV 1  12% Symptoms requiring  1 puff / day of beta agonist Inclusion Criteria Price DB et al Thorax 2003;58:

Study Design Montelukast 10 mg once daily + budesonide 400 µg twice daily Budesonide 800 µg twice daily + montelukast placebo Budesonide 400 µg twice daily Run-in (4 weeks) Single-blind Active treatment (12 weeks) Double-blind 0416 Weeks 1 Montelukast placebo once daily (n=889) (n=448) (n=441) Price DB et al Thorax 2003;58:

Baseline Characteristics Gender (% female) Mean age (years) Mean AM PEF (L/min) Mean FEV 1 (% predicted) Mean daytime symptom score Median % nights with awakenings with asthma Mean daily beta-agonist use (puffs/day) Mean inhaled corticosteroid dose (  g/day) Montelukast + budesonide 800  g (n=448) Budesonide 1600  g (n=441) Price DB et al Thorax 2003;58: Total (N=889)

AM PEF Continued to Improve from Baseline over the Study in Both Treatment Groups Mean AM PEF (L/min) Days after randomisation Montelukast + budesonide 800 µg (n=448) Budesonide 1600 µg (n=441) Run-in Price DB et al Thorax 2003;58: Data represent the mean AM PEF measured before administration of study medication. The efficacy analysis considered the last 10 weeks of the 12-week active treatment period.

Montelukast with Budesonide Had a Faster Onset of Action: Evidence from Day 1 Mean AM PEF (L/min) Days relative to randomisation 420 Run-in Montelukast + budesonide 800 µg (n=448) Budesonide 1600 µg (n=441) p<0.001 between groups Price DB et al Thorax 2003;58:

Mean percentage change from baseline in AM PEF Patients (n) Distribution of Response in AM PEF Montelukast + budesonide 800 µg (n=448) Budesonide 1600 µg (n=441) Price DB et al Thorax 2003;58:

Montelukast with Budesonide Was More Effective in Patients with Comorbid Allergic Rhinitis Data on file, MSD. Montelukast + budesonide 800  gBudesonide 1600  g Change from baseline in AM PEF (L/min) All asthma patientsAsthma patients with confirmed allergic rhinitis p=NS n=433n=425n=216n=184 p=0.028 Results of a post hoc analysis of patients with asthma and allergic rhinitis 53% Additional improvement

Improvement from Baseline in Quality of Life Scores Montelukast + budesonide 800  g (n=448) Budesonide 1600  g (n=441) Mean change from baseline in score *0.5 represents the minimal important difference in Quality of Life Questionnaire score (Juniper EF et al J Clin Epidemiol 1994;47:81-87.) p=0.091 OverallSymptomsActivitiesEmotionalEnvironmental stimuli * Price DB et al Thorax 2003;58:

Average Daily Use of Beta Agonist Mean beta-agonist use (puffs/day) p=0.510 Budesonide 1600  g (n=441) Montelukast + budesonide 800  g (n=448) Weeks after randomisation Price DB et al Thorax 2003;58:

Mean daytime symptom score Average Daytime Asthma Symptom Score p=0.908 Weeks after randomisation Budesonide 1600  g (n=441) Montelukast + budesonide 800  g (n=448) Price DB et al Thorax 2003;58:

Asthma Exacerbations and Asthma-Free Days An asthma exacerbation day was defined as a day with any one of the following events –A decrease from baseline in AM PEF of >20% –AM PEF <180 L/min –An increase from baseline in beta-agonist use of >70% (and a minimum increase of  2 puffs) –An increase from baseline in symptom score of  50% –An asthma attack An asthma-free day was defined as a day free of: –Oral corticosteroid use –Emergency care –Nocturnal awakenings with use of  2 puffs of beta agonist Price DB et al Thorax 2003;58:

Days with Asthma Exacerbations Montelukast + budesonide 800  g (n=448) Median days with asthma exacerbations (%) Budesonide 1600  g (n=441) p= Price DB et al Thorax 2003;58:

Asthma-Free Days during 12 Weeks of Treatment Median asthma-free days (%) Montelukast + budesonide 800  g (n=448) Budesonide 1600  g (n=441) p=0.371 Price DB et al Thorax 2003;58:

Nocturnal Awakenings with Asthma at Baseline and during 12 Weeks of Treatment Median nights with awakenings with asthma (%) Montelukast + budesonide 800  g (n=448) Budesonide 1600  g (n=441) BaselineTreatmentBaselineTreatment 81.3% Fewer nights with awakenings 71.7% Fewer nights with awakenings p= Price DB et al Thorax 2003;58:

Patients Who Discontinued Study Treatment due to Worsening Asthma Patients (n) Montelukast + budesonide 800  g (n=448) Budesonide 1600  g (n=441) 2 7 p=0.105 Price DB et al Thorax 2003;58:

Patients Requiring Oral Steroids or Admission to Hospital Patients (%) Montelukast + budesonide 800  g (n=448) Budesonide 1600  g (n=441) p=0.472 Price DB et al Thorax 2003;58:

Tolerability Profile Adverse events Patients with  1 adverse event Respiratory system adverse events Montelukast + budesonide 800  g (n=448) 37.1% 11.6% Budesonide 1600  g (n=441) 41.3% 16.6% p value ns <0.05 Price DB et al Thorax 2003;58:

Summary In COMPACT, treatment with montelukast 10 mg with budesonide 800  g –Was at least as effective as doubling the budesonide dose to 1600  g –Was more effective than doubling the dose of budesonide in a post hoc substudy of patients with asthma and allergic rhinitis –Had a faster onset of action than doubling the budesonide dose to 1600  g Both treatments were generally well tolerated, with no significant difference in overall incidence of adverse events There was a significantly lower incidence of respiratory adverse events with montelukast with budesonide 800  g compared with budesonide 1600  g (p<0.05) Price DB et al Thorax 2003;58:

References See notes page for references

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