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: