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Nama: dr. Cita Herawati Murjantyo,SpTHT-KL
Tempat/tgl lahir: Yogyakarta, 15 Maret
Pekerjaan/ jabatan:
Kepala Divisi Onkologi THT RS. Kanker Dharmais
Bagian THT-RSI.Bintaro
Riwayat pendidikan formal:
Spesialis THT, FKUI RSCM-1998
Sedang pendidikan S3, Universitas Gajah Mada Yogyakarta
Riwayat pendidikan Tambahan:
Endoscopic and Skull Base Surgery, Masterclass, Milano 2003
OSAS Obstructive Sleep Apnea Syndrome/ SNORING, Singapore General
Hospital, 2006
Head & Neck Course, Singapore General Hospital, 2007
European Allergic Course, Greece, 2008
European Academy of Allergy and Clinical Immunology Congress, Geneva,
2012
Instructional Course Skull Base Surgery, Jakarta, 2013
dr. Cita Herawati,SpTHT
RSK Dharmais
Definition (ARIA):
Allergic rhinitis is a symptomatic disorder of the nose
induced after allergen exposure by an immunoglobulin E (IgE)-
mediated inflammation of the membranes lining the nose
Bousquet J, Allergy 2008: 63 (Suppl. 86): 8–160
ARIA: Allergic Rhinitis and its Impact on Asthma
Allergic rhinitis is characterized by chronic nasal inflammation • IgE-mediated nasal response to allergens results in Mast cell activation
Release of chemical mediators
Influx of inflammatory cells
Early and late phase components
Adcock I, Clin Exp All Rev 2002; 2: 85-8
The classification "seasonal" and "perennial" allergic rhinitis
has been changed to
"intermittent" and "persistent" allergic rhinitis
Allergic Rhinitis:
Classification and
Management
Guideline
INTERMITTENT
<4 days per week or
<4 weeks
PERSISTENT
>4 days per week and
>4 weeks
MILD
Normal sleep and
No impairment of daily
activities, sport, leisure and
Normal work and school and
No troublesome symptoms
MODERATE–SEVERE
One or more items
Abnormal sleep
Impairment of daily activities,
sport, leisure
Impaired work and school
Troublesome symptoms
In untreated patients
Bousquet J et al. J Allergy Clin Immunol 2001;108(Suppl 5):S147–336; ARIA: at a glance pocket reference 2007.
ARIA, Allergic Rhinitis and its Impact on Asthma
ARIA = Allergic Rhinitis and its Impact on Asthma.
Bousquet et al. J Allergy Clin Immunol. 2001;108 (5 suppl):S147.
Mild
intermittent
Moderate
severe
intermittent
Mild
persistent
Moderate
severe
persistent
Immunotherapy
Allergen and irritant avoidance
Intranasal decongestant (<10 days) or oral decongestant
Second-generation nonsedating H1 antihistamine
Leukotriene receptor antagonists
Local cromone
Intra-nasal steroid
ARIA
2008
Intranasal corticosteroids are the most effective drugs and it becomes the first choice for moderate-severe persistent
allergic rhinitis. 1
Treatment may prevent development of co-morbidities
such as asthma, sinusitis or otitis media2,3
1. Bousquet J et al. J Allergy Clin Immunol. 2001;108(Suppl 5):S147–S334 2.Settipane R. Allergy Asthma Proc 1999;20:209–213
3. Crystal-Peters J et al. J Allergy Clin Immunol . 2002;109:57–62
Fluticasone Furoate
Fluticasone furoate: a combination of the fluticasone
backbone
and a 17- furoate ester
CO O
S C H 2 F O
1
7
O
O
F
HO
F
Furoate ester group
Enhanced glucocorticoid
affinity and greater
selectivity
Fluticasone backbone
Biggadike K et al. Ann Allergy Asthma Immunol 2007;98(Suppl 1):A91–A92. Salter M et al. Am J Physiol Lung Cell Mol Physiol
2007;293:L660–L667.
FF is a distinct drug molecule and not a salt or a pro-drug of fluticasone
Valotis A, Högger P. EAACI. 2006, Abstract 780.
Fluticasone furoate
Mometasone furoate
Fluticasone propionate
Beclometha- sone-17- monopropionate
Ciclesonide active principle
Budesonide Dexamethasone
0
500
1000
1500
2000
2500
3000
Re
lati
ve r
ece
pto
r af
fin
ity
(RR
A)
Affinity of INS for the human lung glucocorticoid receptor
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 10
FF
FP
MF
Budesonide
Glucocorticoid concentration (nM)
Salter M et al. Am J Physiol Lung Cell Mol Physiol 2007;293:L660–L667.
Adcock I, Ito K, data on file; Valotis A, Högger P. Respir Res 2007;8:54.
High retention of Fluticasone furoate in tissues enhances its duration of action
Fluticasone furoate (10-10M)
Fluticasone propionate (10-10M)
4 h 30 h
FF remains bound to glucocorticoid receptor
at its cellular site of action for >24 hours
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.
Bioavailability of currently used INS 20%
11%
0.5%0.5%0.5%
0
5
10
15
20
25
Fluticasone
furoate
Fluticasone
propionate
Mometasone
furoate
Budesonide Flunisolide
% b
ioavail
ab
ilit
y
Fluticasone Furoate
-1,2
-1
-0,8
-0,6
-0,4
-0,2
0
FFNS 100mcg
Placebo
LS m
ean c
hange F
FN
S 1
10 µ
g
vers
us
pla
cebo o
ver
treatm
ent
peri
od*
Rhinorrea Nasal
Congestion
Nasal
Itching Sneezing
* * * *
* p<0.001 vs placebo
Maspero JF et al, Allergy Asthma Proc. 2010;31(6):483-92
SAR
Efficacy Studies
Significantly reduced four individual
nasal symptom scores
Global (PAR)
FFNS 110 µg Placebo
Baseline mean daily rTNSS 3.4 3.3
LS mean change FFNS 110 µg
vs placebo over 2-week treatment period*
–1.85
*P<0.001 –1.21
Patients, n 151 151
Significant improvements in QoL
–2.5
–2
–1.5
–1
–0.5
0
Ove
rall
Act
ivit
ies
Sle
ep
No
n-n
ose
sy
mp
tom
s
Pra
ctic
al
pro
ble
ms
No
se
sym
pto
ms
Eye
sy
mp
tom
s
Emo
tio
nal
p
rob
lem
s
RQ
LQ s
core
*
* P<0.001
*
* *
* *
*
*
FFNS 110 µg
Placebo
aGraph data from Global PAR study
PAR
Efficacy Studies
Global Paediatric PAR US Paediatric SAR
FFNS 110 µg FFNS 55 µg Placebo FFNS 110 µg FFNS 55 µg Placebo
Baseline mean daily iTNSS 8.3 8.3 8.3 8.3 8.4 8.4
LS mean change FFNS vs placebo over
2- or 4-week treatment period*
–3.52
*P=0.009
–3.62
*P=0.002 –2.87
–2.80
*P=0.015
–2.37
*P=0.389 –2.13
Patient (n) 146 152 150 146 152 150
US Paediatric SAR Global Paediatric PAR
Placebo
FFNS 55 µg
FFNS 110 µg
28
-6.5
-6.0
-5.5
-5.0
-4.5
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0 21 14 7
0
EP EP 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0
0
-6.0
-5.5
-5.0
-4.5
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
-6.5
Mean c
hange f
rom
base
line in m
ean iT
NSS
Global, FFR30008 Masperó J et al. Otolaryngology–Head and Neck Surgery (2008) 138, 30-37
US, FFR100010 Meltzer EO et al. Pediatr Allergy Immunol 2009: 20: 279–286
CONCLUSION:
Fluticasone Furoate Nasal Spray Once Daily was well tolerated
and demonstrated efficacy in children.
EfficacyStudies
Pooled analysis of adverse
events (AEs) from Three
integrated SAR/PAR studies
Placebo (n=330) FFNS 55 µg
(n=297) FFNS 110 µg
(n=321)
Drug-related AE 10% 7% 8%
AE with an incidence of
≥3% or more common than
placebo, n(%)
Headache 27 (8) 25 (8) 28 (9)
Nasopharyngitis 17 (5) 15 (5) 18 (6)
Pharyngolaryngeal pain 12 (4) 15 (5) 10 (3)
Epistaxis 14(4) 13 (4) 12 (4)
Pyrexia 5 (2) 8 (3) 10 (3)
Meltzer EO et al. Clin Drug Invest 2009; 29 (2): 79-86.
Safety Studies
Seasonal allergic rhinitis
Significant and consistent improvement of nasal symptoms
24-hour efficacy allows once-daily dosing
Proven and consistent efficacy for ocular symptoms
Rapid onset of action
Adults : consistent and significant improvements in QoL
Perennial allergic rhinitis
Significant and consistent improvement of nasal symptoms
24-hour efficacy allows once-daily dosing
Rapid onset of action
Adults : Consistent and significant improvements in QoL
Tolerability
Favourable safety/efficacy ratio
Fluticasone Furoate
Drip down the throat or out through the nose
Taste and smell
Difficulty triggering and handling
Difficult to administer to third parties
Uncomfortable delivery nozzle
Less than 50% of patients think that currently available devices for intranasal steroids are easy to use
Reported weaknesses include:
Berger WE et al. Expert Opin Drug Deliv 2007;4:689–701.
Berger WE et al. Expert Opin Drug Deliv 2007;4:689–701.
Easy to use device
Patient-friendly spray No taste or smell Little or no drip down
the throat (half the spray volume of other intranasal steroids
Gentle spray, a consistent amount each time
Viewing window See how much is left
Easy to grip with side actuation
Comfortable for
patients
Nozzle is short and ergonomically designed
Berger WE et al. Expert Opin Drug Deliv 2007;4:689–701.
An enhanced-affinity glucocorticoid
efficacy
Highly selective for the glucocorticoid
receptor safety
Proven clinical studies for both Seasonal and
Perennial Allergic Rhinitis Symptoms
24-hour duration of action
Unique side-actuated device
Fluticasone furoate:
Recommended