Impact of Allergic Rhinitis (AR) Symptoms on Quality of Life lModerate-to-severe allergic rhinitis...
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Transcript of Impact of Allergic Rhinitis (AR) Symptoms on Quality of Life lModerate-to-severe allergic rhinitis...
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