downloaded from – slide 1 efficacy of montelukast in asthma patients with allergic rhinitis one...

Downloaded from – www.singulair.ae

Efficacy of Montelukastin Asthma Patients

with Allergic Rhinitis

One Airway, One Disease, One Approach


One Airway, One Disease


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.


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



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



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


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


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


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


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


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


• Outdoor allergens– Pollens– Molds

• Indoor allergens– House-dust mites– Animal dander– Insects (e.g., cockroach allergen)

• NSAIDs (e.g., aspirin)


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.



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


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



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)


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



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



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



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)



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



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

*

**


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.



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.


Cysteinyl Leukotrienes—Important Mediators of Both Asthma and Allergic Rhinitis


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)


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



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)


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)



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



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


Histamine


Cytokines

Most commonly associated allergy symptoms

SneezingNasal itchingRhinorrheaNasal obstruction

Prolonged nasal obstruction


Efficacy of Montelukast in Asthma Patients with Seasonal Allergic Rhinitis


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


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



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)


Endpoints




Baseline Characteristics of Patients


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



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


–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


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



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


Global evaluations of allergic rhinitis*p0.001

p0.001



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


Global evaluations of asthma*

p<0.01 p<0.05



Conclusions

ap0.001 vs. placebo; bp<0.01 vs. placebo; cp<0.05 vs. placebo; dp0.005 vs. placebo


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


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.


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


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)


• 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.


• 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


Definition of Groups in Analysis




Baseline Characteristics of Patients


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



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



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)



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.


References

Please see notes page.


References (continued)

Please see notes page.


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

downloaded from – slide 1 efficacy of montelukast in asthma patients with allergic rhinitis one...

Documents

asthma allergic rhinitis

prevalence asthma slide

asthma patients

disease asthma

risk of asthma

disease slide

approach slide

international study