downloaded from – slide 1 efficacy of montelukast in asthma patients with allergic rhinitis one...
TRANSCRIPT
Slide 1Downloaded from – www.singulair.ae
Efficacy of Montelukastin Asthma Patients
with Allergic Rhinitis
One Airway, One Disease, One Approach
Slide 2Downloaded from – www.singulair.ae
One Airway, One Disease
Slide 3Downloaded from – www.singulair.ae
One Airway, One Disease Asthma and Allergic Rhinitis: Two Related Conditions Linked by One Common Airway
• Frequently overlapping conditions
• Involvement of the same tissues
• Common inflammatory processes
– Common inflammatory cells
– Common inflammatory mediators
Adapted from Phillip G et al Curr Med Res Opin 2004;20(10):1549–1558.
Slide 4Downloaded from – www.singulair.ae
Allergic Rhinitis
Epidemiologic Links between Allergic Rhinitis and Asthma
Allergic Rhinitis and Asthma Have Similar Prevalence Patterns
Study of worldwide prevalence of atopic diseases in 463,801 children 13–14 years of age. Children self-reported symptoms over 12 months using questionnaires.
Adapted from the International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee Lancet 1998;351:1225–1232.
UKAustralia
CanadaBrazil
USASouth Africa
GermanyFrance
ArgentinaAlgeria
ChinaRussia
0 5 10 15 20 25 30 35 40
% prevalence
UKAustralia
CanadaBrazil
USASouth Africa
GermanyFrance
ArgentinaAlgeria
ChinaRussia
0 5 10 15 20 25 30 35 40
% prevalence
Asthma
Slide 5Downloaded from – www.singulair.ae
Epidemiologic Links between Allergic Rhinitis and Asthma
Many Patients with Asthma Have Allergic Rhinitis
Adapted from Bousquet J et al J Allergy Clin Immunol 2001;108(suppl 5):S147–S334; Sibbald B, Rink E Thorax 1991;46:895–901; Leynaert B et al J Allergy Clin Immunol 1999;104:301–304; Brydon MJ Asthma J 1996:29–32.
Up to 80% of all asthmatic patients have allergic rhinitis
All asthmatic patients
Slide 6Downloaded from – www.singulair.ae
Epidemiologic Links between Allergic Rhinitis and Asthma
Allergic Rhinitis Is a Risk Factor for Asthma
Allergic rhinitis increased the risk of asthma about threefold
23-year follow-up of first-year college students undergoing allergy testing; data based on 738 individuals (69% male) with average age of 40 years
Adapted from Settipane RJ et al Allergy Proc 1994;15:21–25.
12
10
8
6
4
2
0
% of patients who developed
asthma
10.5
Allergic rhinitisat baseline
(n=162)
3.6
No allergic rhinitisat baseline
(n=528)
p<0.002
Slide 7Downloaded from – www.singulair.ae
Post Hoc Resource Use Analysis of IMPACT
Allergic Rhinitis Increased the Risk of Asthma Attacks
Post hoc analysis of medical resource use/asthma attacks in asthmatic patients with and without concomitant allergic rhinitis over 52 weeksAdapted from Bousquet J et al. Poster presented at the European Academy of Allergology and Clinical Immunology (EAACI), June 12–16, 2004, Amsterdam. Poster 141.
25
20
15
10
0
% of patients
21.3
Patients with asthma+ allergic rhinitis
(n=893)
17.1
Patientswith asthma
(n=597)
p=0.046
Slide 8Downloaded from – www.singulair.ae
Allergic Rhinitis Worsens Asthma
Allergic Rhinitis Doubled the Risk of ER Visits in Patients with Asthma
Post hoc analysis of medical resource use/asthma attacks in asthmatic patients with and without concomitant allergic rhinitis over 52 weeks
ER=emergency roomAdapted from Bousquet J et al. Poster presented at the European Academy of Allergology and Clinical Immunology (EAACI), June 12–16, 2004, Amsterdam. Poster 141.
% of patients
Patients with asthma + allergic rhinitis
(n=893)
Patientswith asthma
(n=597)
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
p=0.029
1.7
3.6
Slide 9Downloaded from – www.singulair.ae
Retrospective Cohort Study of UK Mediplus Database
Allergic Rhinitis Increased the Odds of Hospitalization for Asthma by 50%
Analysis of health-care resource use in adults 16 to 55 years of age with asthma and allergic rhinitis in a general practice in the UKAdapted from Price D et al Clin Exp Allergy 2005, in press.
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
% of patients
hospitalizedannually
0.76
Patients with asthma + allergic rhinitis
(n=4611)
0.45
Patientswith asthma(n=22,692)
p<0.006
Slide 10Downloaded from – www.singulair.ae
Retrospective Cohort Study of UK Mediplus Database
Allergic Rhinitis Increased the Number of Prescriptions for Rescue Therapy (SABA) in Patients with Asthma
Analysis of health-care resource use in adults 16 to 55 years of age with asthma and allergic rhinitis in a general practice in the UKSABA=short-acting beta2-agonists
Adapted from Price D et al Clin Exp Allergy 2005, in press.
Patients with asthma+ allergic rhinitis
(n=4611)
Patients with asthma(n=22,692)
3.33.2
3.1
3.0
2.92.82.72.62.52.4
0
Annualprescriptions
per patient
3.2
2.7
p<0.0001
Slide 11Downloaded from – www.singulair.ae
IgE=immunoglobulin E
Adapted from National Institutes of Health Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention: A Pocket Guide for Physicians and Nurses. Publication No. 95-3659B. Bethesda, MD: National Institutes of Health, 1998; Bousquet J et al J Allergy Clin Immunol 2001;108(suppl 5):S148–S149.
One Airway, One Disease Both Asthma and Allergic Rhinitis Are Inflammatory Conditions
• Asthma is fundamentally a disease of inflammation
– Inflammation of the lower airways causes bronchoconstriction and airway hyperresponsiveness, resulting in asthma symptoms
• Allergic rhinitis is an IgE-mediated inflammatory disorder
– Inflammation of the nasal membranes in response to allergen exposure results in nasal symptoms
Slide 12Downloaded from – www.singulair.ae
• Outdoor allergens– Pollens– Molds
• Indoor allergens– House-dust mites– Animal dander– Insects (e.g., cockroach allergen)
• NSAIDs (e.g., aspirin)
One Airway, One Disease
Allergic Rhinitis and Asthma Have Common Triggers
Adapted from National Institutes of Health Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention: A Pocket Guide for Physicians and Nurses. Publication No. 95-3659B. Bethesda, MD: National Institutes of Health, 1998; Workshop Expert Panel Management of Allergic Rhinitis and its Impact on Asthma (ARIA) Pocket Guide. A Pocket Guide for Physicians and Nurses, 2001.
Slide 13Downloaded from – www.singulair.ae
One Airway, One Disease
Allergic Rhinitis and Asthma Share Common Inflammatory Cells and Mediators
Adapted from Casale TB et al Clin Rev Allergy Immunol 2001;21(1):27–49; Kay AB N Engl J Med 2001;344:30–37.
Early-phaseresponse
Late-phaseresponseT cells
Inflammatorymediators
Allergen
Cytokines
Preformed MediatorsCysteinyl leukotrienes
ProstaglandinsPlatelet-activating factor
Eosinophils
Membrane-bound IgE
Mastcell
Slide 14Downloaded from – www.singulair.ae
Shared Pathophysiology of Allergic Rhinitis and Asthma
Allergic Rhinitis and Asthma Share a Common Inflammatory Process and Occur in the Same Mucosa
Eos=eosinophils; neut=neutrophils; MC=mast cells; Ly=lymphocytes; MP=macrophages
Adapted from Bousquet J et al J Allergy Clin Immunol 2001;108(suppl 5):S148–S149.
Eosinophil infiltration
Allergic rhinitis Asthma
Nasal Mucosa Bronchial Mucosa
Slide 15Downloaded from – www.singulair.ae
One Airway, One Disease
Symptoms Correlate with the Early- and Late-Phase Responses in Allergic Rhinitis and Asthma
Adapted from Varner AE, Lemanske RF Jr. In: Asthma and Rhinitis. 2nd ed. Oxford: Blackwell Science, 2000:1172–1185; Togias A J Allergy Clin Immunol 2000;105(6 pt 2):S599–S604.
(Asthma)
Score for nasal symptoms
SneezingNasal pruritus CongestionRhinorrhea
Time postchallenge (hours)
1Antigen challenge
3–4 8–12 24
Immediate (early) phase Late phase
FEV1
(% change)
Time (hours)
0
50
100
1 10 240 2 3 4 5 6 7 8 9
Upper Airways
Lower Airways
(Allergic rhinitis)
Slide 16Downloaded from – www.singulair.ae
Prevalence of bronchial hyperresponsiveness*
Clinical Links between Allergic Rhinitis and Asthma
Patients with Allergic Rhinitis Experience Increased Bronchial Hyperresponsiveness
Study of bronchial hyperreactivity in patients (mean age 20 years) with hay fever; challenges were performed in the fall of one year and approximately six months later.
*PD20 <1 mg after carbachol challenge
PD=provocation doseAdapted from Madonini E et al J Allergy Clin Immunol 1987;79:358–363..
60
50
40
30
20
10
0
% ofpatients
Out of season
In season
(n=27)
11
48
p<0.02
Slide 17Downloaded from – www.singulair.ae
Clinical Links between Allergic Rhinitis and Asthma
Allergen Challenge to the Nose Increases Bronchial Hyperresponsiveness
Change from baseline in PC20*
Randomized, crossover two-day investigation of the relationship between allergic rhinitis and lower airway dysfunction in patients with allergic rhinitis and asthma (mean age 31.4 years)
PC=postchallenge
*Lower PC20 values indicate greater hyperresponsiveness
Adapted from Corren J et al J Allergy Clin Immunol 1992;89:611–618.
Baseline
3
2
0
Geometricmean PC20
(methacholine,mg/ml)
Placebo (n=5)Allergen (n=5)
0.5 hrpostchallenge
4.5 hrpostchallenge
p=0.011
p=0.0009
Slide 18Downloaded from – www.singulair.ae
Clinical Links between Allergic Rhinitis and Asthma
Many Patients with Asthma Have Nasal Inflammation
Eosinophil counts in the nasal mucosa
Study of whether nasal mucosal inflammation exists in asthma regardless of the presence of allergic rhinitis in atopic subjects 20 to 66 years of ageBars represent median values.Adapted from Gaga M et al Clin Exp Allergy 2000;20:663–669.
18
16
14
12
10
8
6
4
2
0
Eosinophils/field of
nasal biopsy
Rhinitis No rhinitis Control
(n=9) (n=8) (n=10)
p<0.001p<0.001
Asthmatic
Slide 19Downloaded from – www.singulair.ae
Clinical Links between Allergic Rhinitis and Asthma
Inflammatory Changes in the Nasal and Bronchial Mucosa Are Correlated
Study of whether nasal mucosal inflammation exists in asthma regardless of the presence of allergic rhinitis in atopic subjects 20 to 66 years of age
Adapted from Gaga M et al Clin Exp Allergy 2000;20:663–669.
40
35
30
25
20
15
10
5
0
Asthmaticnasal
mucosaeosinophils
0
r=0.851, p<0.001
Asthmatic bronchial mucosa eosinophils
5 10 15 20 25 30
(n=17)
Slide 20Downloaded from – www.singulair.ae
Clinical Links between Allergic Rhinitis and Asthma
Bronchial Allergen Challenge Increases a Marker of Inflammation (Eosinophils) in Nasal and Bronchial Tissues
Evaluation of allergic inflammation in the upper and lower airways after bronchial challenge in nonasthmatic allergic rhinitis patients vs. controls (age range 18–31 years)
T0= before challenge; T24=24 hours postchallenge; ap<0.05; bp<0.01; cp=0.001; dp=0.002
Adapted from Braunstahl G-J et al Am J Respir Crit Care Med 2000;161:2051–2057.
T0
100
80
60
40
20
0
Eosinophils(number cells/
mm2)
Control patients (n=8) Allergic patients (n=8)
T24
T24 T0
1600
1200
800
400
0Unchallenged
left lungAllergen-
challengedright middle
lobe
b
Nasal tissue (lamina propria)
Bronchial tissue (subepithelial layer)
a
c
ad
Slide 21Downloaded from – www.singulair.ae
Clinical Links between Allergic Rhinitis and Asthma
Bronchial Allergen Challenge Increases Systemic Markers of Inflammation
Evaluation of allergic inflammation in the upper and lower airways after bronchial challenge in nonasthmatic allergic rhinitis patients vs. controls (age range 18–31 years)
T0= before challenge; T24=24 hours postchallenge; *p<0.05; **p<0.01
Data presented as median ± range
Adapted from Braunstahl G-J et al Am J Respir Crit Care Med 2000;161:2051–2057.
Control patients (n=8) Allergic patients (n=8)
T0
600
500
400
300
200
100
0
Peripheral blood
eosinophils(106 cells/L)
T24
*
**
Slide 22Downloaded from – www.singulair.ae
Shared Pathophysiology of Allergic Rhinitis and Asthma
Summary• Allergic rhinitis and asthma share several pathophysiologic
characteristics– Common triggers– Similar inflammatory cascade on exposure to allergen– Cysteinyl leukotrienes are common mediators in upper
and lower airway diseases– Similar pattern of early- and late-phase responses– Infiltration by the same inflammatory cells (e.g.,
eosinophils)– Several potential connecting pathways, including
systemic transmission of inflammatory mediators
Adapted from National Institutes of Health Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention: A Pocket Guide for Physicians and Nurses. Publication No. 95-3659B. Bethesda, MD: National Institutes of Health, 1998; Casale TB, Amin BV Clin Rev Allergy Immunol 2001;21(1):27–49; Workshop Expert Panel Management of Allergic Rhinitis and its Impact on Asthma (ARIA) Pocket Guide. A Pocket Guide for Physicians and Nurses. 2001; Kay AB N Engl J Med 2001;344:30–37; Varner AE, Lemanske RF Jr. In: Asthma and Rhinitis. 2nd ed. Oxford, UK: Blackwell Science, 2000:1172–1185; Togias A J Allergy Clin Immunol 2000;105(6 pt 2):S599–S604; Togias A Allergy 1999;54(suppl 57):94–105.
Slide 23Downloaded from – www.singulair.ae
One Airway, One Disease
ARIA Guidelines Recommend a Combined Approach to Managing Asthma and Allergic Rhinitis
• Patients with allergic rhinitis should be evaluated for asthma
• Patients with asthma should be evaluated for allergic rhinitis
• A strategy should combine the treatment of upper and lower airways in terms of efficacy and tolerability
Adapted from Bousquet J et al J Allergy Clin Immunol 2001;108(suppl 5):S147–S334.
Slide 24Downloaded from – www.singulair.ae
Cysteinyl Leukotrienes—Important Mediators of Both Asthma and Allergic Rhinitis
Slide 25Downloaded from – www.singulair.ae
Inhibit steroid-sensitive mediators
(e.g., cytokines)
Montelukast
Cysteinyl Leukotrienes in Asthma: Dual Pathways of Inflammation Montelukast Combined with a Steroid Affects the Dual Pathways of Inflammation
The slide represents an artistic rendition.Adapted from Diamant Z, Sampson AP Clin Exp Allergy 1999;29:1449–1453; Barnes PJ Am J Respir Crit Care Med 1996;154:S21–S27; Claesson H-E, Dahlén S-E J Intern Med 1999;245:205–227; Price DB et al Thorax 2003;58:211–216.
Inhaled steroids
Inhibits cysteinylleukotrienes
Cysteinylleukotrienes
Steroid-sensitivemediators
(e.g., cytokines)
Slide 26Downloaded from – www.singulair.ae
Study of the use of induced sputum to assess airway eicosanoid production in 10 healthy and 26 asthmatic adults (mean age 40 to 57 years in each treatment group)
*p<0.02 vs. normal individuals; **p<0.05 vs. normal individuals Adapted from Pavord ID et al Am J Respir Crit Care Med 1999;160:1905–1909.
14
12
10
8
6
4
2
0
Sputumcysteinyl
leukotriene levels(ng/ml)
Controls(n=10)
6.4
All patients with asthma
(n=26)
9.4*
Patients with persistent
asthma(n=10)
11.4**
Patients with acute attacks
(n=12)
13*
Cysteinyl Leukotrienes—Mediators of Asthma
Inhaled Corticosteroids Do Not Affect Sputum Leukotriene Levels in Patients with Asthma
Slide 27Downloaded from – www.singulair.ae
Cysteinyl Leukotrienes—Mediators of Asthma
Cysteinyl Leukotrienes Are Important Mediators of Nasal Obstruction
Study to examine the clinical significance of LTD4 versus antigen and histamine in adult patients (mean age 25.0–26.4 in each group). Nasal provocations were carried out with serially increasing doses of LTD4, histamine, or antigen.
*p<0.05 vs. baseline
NAR=nasal airway resistanceAdapted from Okuda M et al Ann Allergy 1988;60:537–540.
%change
inNAR
Challenge
**
Hour
150
125
100
1/2 1 3 5 7 9 11
• LTD4 was approximately 5000 times more potent than histamine in mediating
nasal responses
(n=7)
Slide 28Downloaded from – www.singulair.ae
Cysteinyl Leukotrienes—Mediators of Both Asthma and Allergic Rhinitis
Cysteinyl Leukotriene ChallengeIncreases Rhinorrhea in Allergic Rhinitis
Study to examine the clinical significance of LTD4 versus antigen and histamine in adult patients (mean age 25.0 –26.4 in each group). Nasal provocations were carried out with serially increasing doses of LTD4, histamine, or antigen.Adapted from Okuda M et al Ann Allergy 1988;60:537–540.
Nasal secretion
(10-2 g/min)
0 ~5 ~10 ~15 ~20
Time (minutes)
1.00
0.75
0.50
0.25
0
(n=8)
Slide 29Downloaded from – www.singulair.ae
Cysteinyl Leukotrienes—Mediators of Asthma
Role of Cysteinyl Leukotrienes in Early- and Late-Phase Allergic Response
PAF=platelet-activating factor
Adapted from Togias A J Allergy Clin Immunol 2000;105(6 pt 2):S599–S604; Rachelevsky G J Pediatr 1997;131:348–355; Rouadi P, Naclerio R. SRS-A to Leukotrienes: The Dawning of a New Treatment. S Holgate, S Dahlen, eds. Oxford, England: Blackwell Science, 1997; Creticos PS et al N Engl J Med 1984;31:1626–1630.
Score for nasal
symptomsSneezing
Nasal pruritus CongestionRhinorrhea
Antigen challenge 1 3–4 8–12
Time postchallenge (hours)
Early phaseHistamine, cysteinyl leukotrienes, prostaglandins, thromboxanes,heparin, proteases, PAF
Late phaseCysteinyl leukotrienes,cytokines (predominant)
24
Cysteinyl leukotrienes
Slide 30Downloaded from – www.singulair.ae
Cysteinyl Leukotrienes—Mediators of Asthma
Correlation of Cysteinyl Leukotriene Release with Symptoms in Allergic Rhinitis
Adapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558; Bousquet J et al J Allergy Clin Immunol 2001;108(suppl 5):S147–S334; Sibbald B, Rink E Thorax 1991;46:895–901; Leynaert B et al J Allergy Clin Immunol 1999;104:301–304; Brydon MJ Asthma J 1996:29–32; Vignola AM et al Allergy 1998;53:833–839; Meltzer EO Ann Allergy Asthma Immunol 2000;84(2):176–185; Casale TB, Amin BV Clin Rev Allergy Immunol 2001;21(1):27–49; Settipane GA Arch Intern Med 1981;141:328–332; Magnan A et al Eur Respir J 1998;12:1073–1078; Yssel H et al Clin Exp Allergy 1998;5:104–109, discussion 17–18.
Early-phase allergic response
(within minutes)
Late-phase allergic response
(within 4+ hours)
Predominant mediator types
Cysteinyl leukotrienes
Histamine
Cysteinyl leukotrienes
Cytokines
Most commonly associated allergy symptoms
SneezingNasal itchingRhinorrheaNasal obstruction
Prolonged nasal obstruction
Slide 31Downloaded from – www.singulair.ae
Efficacy of Montelukast in Asthma Patients with Seasonal Allergic Rhinitis
Slide 32Downloaded from – www.singulair.ae
Placebo (n=416)
Placebo
Montelukast* (n=415)
–3 to 5 days 0 2 weeks
Period ISingle-blind run-in
Period IIDouble-blind treatment
Clinical Study of Asthma Patients with Concomitant Seasonal Allergic Rhinitis Study Design and Objective
*10 mg once daily at bedtime
Short-acting beta2-agonists were used as needed in both groups.
Adapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558.
• To evaluate the efficacy of montelukast in improving the symptoms of allergic rhinitis in patients with active asthma and active allergic rhinitis during the allergy season
Slide 33Downloaded from – www.singulair.ae
Clinical Study of Asthma Patients with Concomitant Seasonal Allergic Rhinitis
Inclusion Criteria: Active Asthma and Daily Rhinitis Symptoms
Asthma1-year history (dyspnea, wheezing, chest tightness, cough)1 of 4 criteria for active asthma
– Asthma symptoms once weekly– Reversible airway obstruction– History of methacholine hyperresponsiveness 1-year history of exercise-induced bronchoconstriction
• Stable dose of inhaled corticosteroid and/or long-acting beta2-agonist use
Allergic Rhinitis2-year clinical history (rhinitis symptoms worsening during allergy season)
• Daily rhinitis symptoms at least mild to moderate during placebo run-in
• Positive skin test to 3 allergens active during study season
Adapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558.
Slide 34Downloaded from – www.singulair.ae
Daytime nasal symptoms• Congestion • Rhinorrhea• Pruritus• Sneezing
Nighttime symptoms• Difficulty falling asleep• Nighttime awakenings• Nasal congestion on awakening
Composite Daily Rhinitis Symptom Score
Secondary/other endpoints• Rhinoconjunctivitis quality of life• Patients’ and physicians’ global evaluations of allergic rhinitis • Patients’ and physicians’ global evaluations of asthma• As-needed beta2-agonist use
(0–3 scale, mild to severe)
Clinical Study of Asthma Patients with Concomitant Seasonal Allergic Rhinitis
Endpoints
Adapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558.
Slide 35Downloaded from – www.singulair.ae
Clinical Study of Asthma Patients with Concomitant Seasonal Allergic Rhinitis
Baseline Characteristics of Patients
Adapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558.
Montelukast(n=415)
Placebo(n=416)
Age (years) Mean±SD Range
33.013.215–78
33.613.715–80
Gender (% of patients) Male Female
36%64%
35%65%
Duration of allergic rhinitis (years) 19.611.9 19.012.2
Duration of asthma (years) 17.512.2 16.511.9
Inhaled corticosteroid therapy at baseline (% of patients) 38% 43%
Asthma symptoms once weekly (% of patients) 90% 93%
Asthma symptoms twice weekly (% of patients) 57% 62.5%
Season studied (% of patients) Spring Fall
84%16%
85%15%
FEV1 (% predicted) 84% 84%
Daily rhinitis symptoms score 1.750.42 1.770.42
Slide 36Downloaded from – www.singulair.ae
Clinical Study of Asthma Patients with Concomitant Seasonal Allergic Rhinitis
Montelukast Significantly Reduced Daily Rhinitis Symptoms Scores*
Multicenter study of the effects of montelukast 10 mg on allergic rhinitis in asthmatic patients 15 to 85 years of age with allergic rhinitis during the allergy season
*Scored on a 4-point scaleAdapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558.
0
–0.1
–0.2
–0.3
–0.4
–0.5
Changefrom
baseline(mean)
–11%
Daily rhinitissymptoms
Daytime nasalsymptoms
Nighttimesymptoms
–18%–10.5%
–18.7%
–11.8%
–18.2%
Placebo (n=416)Montelukast (n=415)
p0.001
p0.001
p0.001
Slide 37Downloaded from – www.singulair.ae
–0.3
–0.2
–0.1
0
NoYes <80% 80% 12% <12% twiceweekly
<twiceweekly
n=335 n=490 n=495 n=330 n=316 n=503 n=427 n=392
On inhaled corticosteroids
Gre
ate
r
Eff
ec
t
Clinical Study of Asthma Patients with Concomitant Seasonal Allergic Rhinitis
Montelukast Reduced Daily Rhinitis Symptoms Regardless of Asthma Status at Study Start
Multicenter study of the effects of montelukast 10 mg on allergic rhinitis in asthmatic patients 15–85 years of age with allergic rhinitis during the allergy seasonAdapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558.
Asthmasymptoms
Treatmentdifference:
montelukastminus
placebo(LS meanSE)
FEV1
% predictedBeta-agonistreversibility
Slide 38Downloaded from – www.singulair.ae
Clinical Study of Asthma Patients with Concomitant Seasonal Allergic Rhinitis
Montelukast Improved Global Evaluations of Clinical Status and Quality of Life
• Montelukast significantly improved rhinoconjunctivitis quality-of-life scores versus placebo (p<0.01)
Multicenter study of the effects of montelukast 10 mg on allergic rhinitis in asthmatic patients 15–85 years of age with allergic rhinitis during the allergy season*Scored on a 6-point scaleAdapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558.
5
4
3
2
1
0
Treatmentscore
(mean±SD)
PhysiciansPatients
2.772.39 2.76
2.41
Placebo (n=416)Montelukast (n=415)
Global evaluations of allergic rhinitis*p0.001
p0.001
Slide 39Downloaded from – www.singulair.ae
Clinical Study of Asthma Patients with Concomitant Seasonal Allergic Rhinitis
Montelukast Improved Asthma Control
Multicenter study of the effects of montelukast 10 mg on allergic rhinitis in asthmatic patients 15–85 years of age with allergic rhinitis during the allergy season
*Scored on a 6-point scaleAdapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558.
• Montelukast significantly reduced beta2-agonist use (p0.005 vs. placebo)
2.8
2.6
2.4
2.2
0
Treatmentscore
(mean)
PhysiciansPatients
2.52
2.28
2.52
2.34
Placebo (n=416)Montelukast (n=415)
Global evaluations of asthma*
p<0.01 p<0.05
Slide 40Downloaded from – www.singulair.ae
Clinical Study of Asthma Patients with Concomitant Seasonal Allergic Rhinitis
Conclusions
ap0.001 vs. placebo; bp<0.01 vs. placebo; cp<0.05 vs. placebo; dp0.005 vs. placebo
Adapted from Philip G et al Curr Med Res Opin 2004;20(10):1549–1558.
In asthmatic patients with concomitant seasonal allergic rhinitis,montelukast demonstrated significant improvements in
• Allergic Rhinitis– Daily rhinitis symptoms score (average of the daytime nasal
symptoms score and the nighttime symptoms score)a
– Rhinoconjunctivitis quality of lifeb
– Global evaluations of allergic rhinitis by patient and by physiciana
• Asthma– Global evaluations of asthma by patientb and by physicianc
– Beta2-agonist used
Slide 41Downloaded from – www.singulair.ae
Objective of COMPACT Study and Subanalysis
• To determine whether adding montelukast 10 mg to
budesonide (800 µg) would provide greater benefits
than doubling the dose of budesonide (to 1600 µg) in
– Adult patients with asthma (OVERALL study)
– Patients with asthma and allergic rhinitis
(SUBGROUP analysis)
COMPACT=Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy
Adapted from Price DB et al Thorax 2003;58:211–216; Price DB et al. Presentation at the World Allergy Organization Biannual Meeting, September 2003, Vancouver, British Columbia, Canada.
Slide 42Downloaded from – www.singulair.ae
COMPACT Study Design
Adapted from Price DB et al Thorax 2003;58:211–216.
Budesonide 400 µg
twice daily
Montelukast 10 mg once daily +
Budesonide 400 µg twice daily (n=448)
0 4 16
Period IRun-in (4 weeks)
Single-blind
Period IIActive treatment (12 weeks)
Double-blind
1 8 12
Budesonide 800 µg twice daily +
Oral placebo montelukast (n=441)
Weeks
Slide 43Downloaded from – www.singulair.ae
440
430
420
410
400
390
380
PEF=peak expiratory flow
*Mean measurement before administration of study medication
Adapted from Price DB et al Thorax 2003;58:211–216.
COMPACT Study Montelukast + Budesonide Improved Morning PEF Progressively over 12 Weeks
MorningPEF*
(L/min)
–14 14 84
Days after randomization
–7 0 7 21 28 35 42 56 63 70 77
Montelukast 10 mg + budesonide 800 µg (n=448) Budesonide 1600 µg (n=441)
Slide 44Downloaded from – www.singulair.ae
• All patients with a baseline and at least one
on-treatment value were included in this intention-to-treat
analysis
• Treatment comparisons were based on an analysis
of covariance (ANCOVA) model, with corresponding
baseline value included as a covariate and the treatment
group as a factor
• All analyses of patient subgroups were post hoc
Subanalysis of Asthma Patients with Concomitant Allergic Rhinitis in COMPACT
Statistical Analysis
Adapted from Price DB et al. Presentation at the World Allergy Organization Biannual Meeting, September 2003, Vancouver, British Columbia, Canada.
Slide 45Downloaded from – www.singulair.ae
• Asthma+AR Patients with asthma and allergic rhinitis, defined by both positive patient history and confirmed physician diagnosis
• Asthma–ARPatients with asthma but without both a patient history and physician diagnosis of allergic rhinitis
Subanalysis of Asthma Patients with Concomitant Allergic Rhinitis in COMPACT
Definition of Groups in Analysis
Adapted from Price DB et al. Presentation at the World Allergy Organization Biannual Meeting, September 2003, Vancouver, British Columbia, Canada.
Slide 46Downloaded from – www.singulair.ae
Subanalysis of Asthma Patients with Concomitant Allergic Rhinitis in COMPACT
Baseline Characteristics of Patients
Adapted from Price DB et al. Presentation at the World Allergy Organization Biannual Meeting, September 2003, Vancouver, British Columbia, Canada.
Asthma +Allergic Rhinitis
(n=410)Asthma(n=479)
Age (years) Median Range
4315–74
4515–75
Gender (% of patients) Male Female
42 58
38 62
Duration of asthma (years) 15 13
Median morning PEF (L/min) 381 360
History of exercise-induced asthma(% of patients)
83 80
Skin tested for allergies (% of patients) 74 58
History of atopic dermatitis (% of patients)
19 12
Slide 47Downloaded from – www.singulair.ae
Subanalysis of Asthma Patients with Concomitant Allergic Rhinitis in COMPACT
Montelukast Provided Greater Improvements in Morning PEF in Asthma Patients with Concomitant Allergic Rhinitis
50
40
30
20
10
0
Change from baseline
(L/min, LS meanSEM)
0 4 8 12 0 4 8 12
Montelukast (n=433)* Budesonide (n=425)**
p<0.03
p=0.36
Weeks Weeks
Montelukast (n=216)* Budesonide (n=184)**
*Montelukast 10 mg once daily + budesonide 400 µg twice daily; **Budesonide 800 µg twice dailyAdapted from Price DB et al. Presentation at the World Allergy Organization Biannual Meeting, September 2003, Vancouver, British Columbia, Canada.
50
40
30
20
10
0
Slide 48Downloaded from – www.singulair.ae
Subanalysis of Asthma Patients with Concomitant Allergic Rhinitis in COMPACT
Conclusion
• In the subgroup of asthma patients from the COMPACT study who had concomitant allergic rhinitis, the addition of montelukast to budesonide provided greater improvements in reducing airway obstruction than doubling the dose of budesonide– Improvements in morning PEF were similar in both
treatment groups (primary endpoint)
Adapted from Price DB et al. Presentation at the World Allergy Organization Biannual Meeting, September 2003, Vancouver, British Columbia, Canada.
Slide 49Downloaded from – www.singulair.ae
Montelukast in Asthma Patients with Concomitant Allergic Rhinitis
Summary
• Allergic rhinitis and asthma are inflammatory disorders that have been linked epidemiologically, pathophysiologically, and clinically as “one airway disease”
• Allergic rhinitis increases morbidity, therapeutic needs, and use of health-care resources in patients with asthma
• ARIA recommends a combined strategy for the management of coexistent allergic rhinitis and asthma when possible
• Cysteinyl leukotrienes are mediators of both allergic rhinitis and asthma
• The cysteinyl leukotriene modifier montelukast has been shown to improve lung function, symptoms, and quality of life in asthma patients with concomitant seasonal allergic rhinitis
Adapted from National Institutes of Health Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention: A Pocket Guide for Physicians and Nurses. Publication No. 95-3659B. Bethesda, MD: National Institutes of Health, 1998; Bousquet J et al J Allergy Clin Immunol 2001;108(suppl 5):S148–S149; Casale TB, Amin BV Clin Rev Allergy Immunol 2001;21(1):27–49; Philip G et al Curr Med Res 2004;20(10):1549–1558; Price DB et al. Presentation at the World Allergy Organization Biannual Meeting, September 2003, Vancouver, British Columbia, Canada.
Slide 50Downloaded from – www.singulair.ae
References
Please see notes page.
Slide 51Downloaded from – www.singulair.ae
References (continued)
Please see notes page.
Slide 52Downloaded from – www.singulair.ae
References (continued)
Please see notes page.
Slide 53Downloaded from – www.singulair.ae
References (continued)
Please see notes page.
Slide 54Downloaded from – www.singulair.ae
Efficacy of Montelukast in Asthma Patients with Allergic Rhinitis
Before prescribing, please consult the manufacturers’ prescribing information.
Copyright © 2004 Merck & Co., Inc., Whitehouse Station, NJ, USA.
All rights reserved. 1-06 SGA 2004-W-6776-SS Printed in USA
VISIT US ON THE WORLD WIDE WEB AT http://www.merck.com