Impact of Allergic Rhinitis (AR) Impact of Allergic Rhinitis (AR) Symptoms on Quality of Life Symptoms on Quality of Life

Moderate-to-severe allergic rhinitis symptoms are associated with– Fatigue and daytime somnolence1–3

– Daily activity impairment4,5

– Reduced work productivity4–8

– Disturbed cognitive functions9

– Reduced learning abilities10,11

– Adverse effects on adolescent behaviour6

1. Borres MP et al. Ann Allergy Asthma Immunol 1997; 78: 29–34; 2. Craig TJ et al. J Allergy Clin Immunol 2005; 116: 1264–1266; 3. Young T et al. J Allergy Clin Immunol

1997; 99: S757–S762; 4. Reilly MC et al. Clin Drug Invest 1996; 11: 278–288; 5. Tanner et al. Am J Manag Care 1999; 5(Suppl 4): S235–S247; 6. Juniper EF et al. J Allergy Clin Immunol 1994; 93: 413–423; 7. Corey JP et al.

Otolaryngol Head Neck Surg 2000; 122: 681–685; 8. Blanc PD et al. J Clin Epidemiol 2001; 54: 610–618; 9. Marshall PS and Colon EA. Ann Allergy 1993; 71: 251–258; 10. Vuurman EF et al.

Ann Allergy Asthma Immunol 1996; 76: 247–252; 11. Walker S et al. Eur Respir J 2005; 26(Suppl 49): 134s.

Epidemiology Of Epidemiology Of Allergic Allergic RhinitisRhinitis

Allergic rhinitis was reported the second most prevalent chronic condition in the United States in 1994

Affects 40 to 50 million people

Incidence highest in people ages 15-25 years

Prevalence of Allergic Rhinitis is Increasing

“Do you suffer from, or have you ever suffered from, hay fever?”Location: Paisley and Renfrew, UK

0

5

10

15

20

25

1972-76 1996

Year

Pre

vale

nce

(%

)

Men Women

Despite Available Treatment Nasal Despite Available Treatment Nasal Symptom Burden Remains HighSymptom Burden Remains High

During an allergy season AR symptom sufferers have During an allergy season AR symptom sufferers have a large nasal symptom burden despite the availability of a large nasal symptom burden despite the availability of

over-the-counter and prescription treatmentsover-the-counter and prescription treatments

Nathan RA et al. AAAAI 2006.

Nasal symptom control over past 4 weeks

9.7%

29.5%

44.1%

14.1%

2.5%0

10

20

30

40

50

Completely Well Somewhat Unchanged Worsened

% p

op

ula

tio

n (

n=

7069

)

Hay Fever Symptoms Have a Significant Hay Fever Symptoms Have a Significant Impact on Exam PerformanceImpact on Exam Performance

A case-control study in UK students sitting national exams in three subjects (May–June 2004)

36% (673/1862) dropped at least one grade in at least one subject compared with winter exam

Cases (dropped at least one grade)

(n=673)

Controls(n=1189)

Mean diff(95% Cl)

Hay fever symptoms, n (%)389

(59.9%)623

(53.9%)5.4%*

(0.7-10.1)

*P=0.001

Walker S et al. Eur Respir J 2005; 26(Suppl 49): 134s.

Očesni simptomi so pomembni pri Očesni simptomi so pomembni pri zdravljenju alergijskega rinitisazdravljenju alergijskega rinitisa

Nasal only28%

Ocular only1%

Nasal &

ocular71%

71% bolnikov trpi zaradi očesnih

simptomov

71% bolnikov trpi zaradi očesnih

simptomov

Mono39%

Triple9%

Dual52%

50% jemlje več zdravil za AR

50% jemlje več zdravil za AR

Majority of these still not satisfied with treatment

Anti-histamines are not effective enough on nasal symptoms

Current INSs do not work on eye symptoms

Systemic availability of INSSystemic availability of INS

Brand PL. Eur Resp J 2001;287–94.Daley-Yates PT, Richards DH. Clin Ther 2004;26:1905–19.

Influenced by: INS bioavailability Degree of first-pass

inactivation in liver

Systemic availability via swallowed portion

Systemic availability via lungs

Nose

LiverHepatic inactivation

(first-pass metabolism)

Pharynx

Stomach

OesophagusLungs

Nazalno okularni živčni refleksNazalno okularni živčni refleks

1. FF ima visoko afiniteto do glukokortikoidnega receptorja1-3

2. To lahko povzroči boljšo inhibicijo nasalno okularnega refleksnega mehanizma

3. Sproščanje mediatorjev, ki povzročajo okularne simptome je zmanjšano

Fluticasone furoate: Fluticasone furoate: glukokortikoid z večjo glukokortikoid z večjo afiniteto do receptorjevafiniteto do receptorjev

Valotis A, Högger P. EAACI 2006, Abstract 780.

Fluticasone furoate

Mometasone furoate

Fluticasone propionate

Beclometha-sone-17-

monopropionate

Ciclesonide active

principle

BudesonideDexamethasone

0

500

1000

1500

2000

2500

3000

Re

lati

ve

re

ce

pto

r a

ffin

ity

(R

RA

)

Fluticasone furoate: a novel moleculeFluticasone furoate: a novel molecule

F

OO

OF

HO

F

Fluticasone furoate

Fluticasone propionate (FP)

OO

OF

HOCO

O

17

Mometasone furoate (MF)

HO

CH2CI

OO

O

O CI

SCH2FSCH2F

COCH2CH3

Fluticasone furoate is a different active chemical entityfrom fluticasone propionate or mometasone furoate

O

Biggadike K et al. EAACI 2006, Abstract 783.Biggadike K et al. J Med Chem 2008;51:3349–52.

Fluticasone furoate tissue retention in Fluticasone furoate tissue retention in human lung epithelial cellshuman lung epithelial cells

30 h

Fluticasone furoate (10-10M)

Fluticasone propionate (10-10M)

4 h

Adcock I, Ito K, data on file.Valotis A, Högger P. Respir Res 2007;8:54.

High retention of fluticasone furoatein tissues enhances its duration of action

Fluticasone furoate remains bound to glucocorticoid receptorat its cellular site of action for >24 hours

Fluticasone furoate shows greatestFluticasone furoate shows greatestin vitro in vitro cell retentioncell retention

20

0

60

40

Ep

ith

elia

l ce

ll a

sso

ciat

ion

aft

er6

ho

urs

(%

of

tota

l re

cove

red

)

FF FPMF Budesonide Flunisolide Triamcinolone acetonide

Salter M et al. Am J Physiol Lung Cell Mol Physiol 2007;293:L660–L667.

Fluticasone furoate shows enhanced Fluticasone furoate shows enhanced affinity for the glucocorticoid receptoraffinity for the glucocorticoid receptor

Valotis A, Högger P. Respir Res 2007;8:54.Salter M et al. Am J Physiol Lung Cell Mol Physiol 2007;293:L660–L667.

855

1212

2244

1775

2988

100

0 500 1000 1500 2000 2500 3000 3500

Fluticasone furoate

Fluticasone propionate

Mometasone furoate

Ciclesonide active principle

Relative Receptor Affinity (RRA)

Dexamethasone

Budesonide

FF has the highest GR affinity compared with other currently available INS

Fluticasone furoate – Fluticasone furoate – nudi boljšo zaščito pred nudi boljšo zaščito pred poškodbo celicpoškodbo celic

Salter M et al. Am J Physiol Lung Cell Mol Physiol 2007;doi:10.1152/ajplung.00108.2007.

Fluticasone furoate: highly selective for GRFluticasone furoate: highly selective for GR

Salter M et al. Am J Physiol Lung Cell Mol Physiol 2007;293:L660–L667.

0 10 20 30 40 50 500 600 700

Fluticasone propionate

Fluticasone furoate

Human steroid hormone receptor selectivity

Mometasone furoate

Ciclesonide active principle

Budesonide

800 900

Mineralocorticoid receptor

Progesterone receptor-b

FF has greater selectivity for the GR than other INS

Lower selectivity for GR Greater selectivity for GR1:1 800:1

Fluticasone furoate: protection against Fluticasone furoate: protection against mechanically induced inflammatory damagemechanically induced inflammatory damage

Wo

un

d a

rea

(% o

f co

ntr

ol)

120

110

100

90

80

70

60

50

40

30

20

0.001 0.01 0.1 1 10Glucocorticoid concentration (nM)

Salter M et al. Am J Physiol Lung Cell Mol Physiol 2007;293:L660–L667.

Fluticasone furoate

Fluticasone propionate

Mometasone furoate

Budesonide

Fluticasone furoate: low bioavailabilityFluticasone furoate: low bioavailability

Bryson HM, Faulds D. Drugs 1992;43:760–75.Daley-Yates PT, Baker RC. Br J Clin Pharmacol 2001;51:103–5.

Daley-Yates PT et al. Eur J Clin Pharmacol 2004;60:265–8.Allen A et al. Clin Ther 2007;29:1415–20.

20%

11%

0.5%0.5%0.5%0

5

10

15

20

25

Fluticasonefuroate

Fluticasonepropionate

Mometasonefuroate

Budesonide Flunisolide

% b

ioav

aila

bil

ity

Bioavailability of currently used INS

Nazalno okularni živčni refleksNazalno okularni živčni refleks

1. FF ima visoko afiniteto do glukokortikoidnega receptorja1-3

2. To lahko povzroči boljšo inhibicijo nasalno okularnega refleksnega mehanizma

3. Sproščanje mediatorjev, ki povzročajo okularne simptome je zmanjšano

Delivery system is designed to meet the Delivery system is designed to meet the needs of patientsneeds of patients

Easy to use device

Patient-friendly sprayNo taste or smellLittle or no drip down

the throat (half the spray volume of other intranasal steroids

Gentle spray, a consistent amount each time

Viewing windowSee how much is left

Easy to grip with side actuation

Comfortable for patients

Nozzle is short and ergonomically designed