Role of INS in the treatment

of Allergic Rhinitis (AR)

For Health Care Professional only

ID/ALG/0002/17 AD: XX/XX/2017 ED: XX/XX/2019
Classification and impact
of AR
Allergic rhinitis (AR)

• “Rhinitis is defined as an inflammation of the lining

of the nose and is characterised by nasal symptoms
including anterior or posterior rhinorrhoea, sneezing, nasal
blockage and/or itching of the nose…
It is often associated with ocular symptoms.”1

1. Bousquet J et al. Allergy 2008: 63 (Suppl. 86): 8–160

Modern classification of AR*1

Intermittent symptoms Persistent symptoms

● <4 days per week ● ≥4 days per week
● Or <4 weeks ● And ≥4 weeks

Mild Moderate/severe
● Normal sleep One or more items
● Normal daily activities, sport, leisure ● Abnormal sleep
● Normal work and school ● Impairment of daily activities
● No troublesome symptoms ● Problems caused at work or school
● Troublesome symptoms

* This figure from the ARIA guidelines (www.whiar.org) is used with the permission of ARIA
1. Bousquet J et al. Allergy 2008: 63 (Suppl. 86): 8–160
Symptoms of AR
• In AR, the immediate reaction resulting from IgE-mediated
mast cell degranulation and mediator release is rapid and
leads to:1
– Sneezing
– Rhinorrhoea
– Itching
– Nasal blockage
• The late-phase reaction involves inflammation, with an
eosinophilic infiltrate.1 Symptoms include:
– Chronic obstruction
– Hyposmia
– Post-nasal mucous discharge
– Nasal hyper-reactivity

1. Hansen I et al. Curr Opin Allergy Clin Immunol 2004; 4:159–63

Global prevalence
and burden of AR
Prevalence of children 6-7 years with
rhinoconjunctivitis symptoms – ISAAC Study*1

* Adapted from Ait-Khaled N et al. 2009

1. Ait-Khaled N et al. Allergy 2009;64:123-148

Prevalence of adolescences ages 13-14 yr with
rhinoconjunctivitis symptoms – ISAAC Study*1

* Adapted from Ait-Khaled N et al. 2009

1. Ait-Khaled N et al. Allergy 2009;64:123-148

Prevalence of Allergic Rhinitis (AR) in Asia Pacific

30
24.2
25 22.6
21

20 17.7 17.6 17.8

16.2 16.5

15
11.6
10.6 10.4
10 8.7 8.7
6-7 years old
4.8 4.8
5 3.6
13-14 years old
0

1. Asher et al, Lancet 2006; 368: 733–43

AR burden on patient health related quality of life
(HRQL)1
Issues in adult rhinitis patients include:1 Issues in paediatric patients include:1
– Fatigue − Learning impairment
– Decrease in energy − Anxiety
− Family dysfunction
– General health perception
– Social function

Impairment of HQRL generally increases with increasing degree of symptoms

and severity of disease1

1. Meltzer EO. J Allergy Clin Imunol. 2001;108:S45-53

AR reduces learning ability in children1

1. Vuurman EFPM et al. Ann Allergy 1993;71:121-126 Graph adapted from Vuurman et al. 1993
Comorbidities and consequences

1. Pawankar RP, et al. WAO white book on allergy.

Children with AR have a high rate of
comorbidities

1. Bertelsen RJ et al. Pediatr Allergy Immunol 2010;21:612-622 Graph adapted from Bertelsen et al. 2010
AR is a stronger predictor of asthma than atopy1

1. Shaaban R et al. Lancet. 2008;372:1049-1057 Graph adapted from Shaaban et al 2008

16
Role of INS in the treatment of
AR
ARIA Guidelines: recommendations for
management of AR1

1. Bousquet J et al. Allergy 2008;63:8-160 Table adapted from Bousquet et al. 2008
ARIA recommendations for intranasal
glucocorticosteroids for treatment of AR1

• ARIA recommend intranasal glucocorticosteroids for

treatment of AR in adults1

• ARIA suggest intranasal corticosteroids in children with AR1

1. Brozek JL et al. J Allergy Clin Immunol 2010;126:466-76

Intranasal steroids1

• Cortisol
• Budesonide
• Beclomethasone dipropionate
• Triamcinolone acetonide
• Flunisolide
• Fluticasone furoate
• Mometasone furoate
• Fluticasone propionate
• Ciclesonide
• Desisobutyryl-ciclesonide

1. Derendorf H and Meltzer EO. Allergy 2008;63:1292-1300

Avamys (fluticasone furoate): an enhanced
affinity glucocorticoid1,2
• Avamys : a combination of the fluticasone backbone and a
17-α furoate ester1,2

Avamys is a distinct drug molecule and not a salt or a pro-drug of fluticasone2

1. Biggadike K et al. Ann Allergy Asthma Immunol 2007;98:91–A92

2. Salter M et al. Am J Physiol Lung Cell Mol Physiol 2007;293:L660–L667
Avamys shows enhanced affinity for the
glucocorticoid receptor*1,2

Avamys has the highest glucocorticoid receptor affinity compared with other currently available
Intranasal corticosteroids (the clinical significance of this is unknown)2
1. Valotis A and Högger P. Respir Res 2007;8:54-63
2. Salter M et al. Am J Physiol Lung Cell Mol Physiol 2007;293:L660–L667
Avamys enhances affinity by making effective
contact with the glucocorticoid receptor*1,2

1. Biggadike K et al. Ann Allergy Asthma Immunol 2007;98:A91–A92

2. Salter M et al. Am J Physiol Lung Cell Mol Physiol 2007;293:L660–L667
Significant and consistent improvement of nasal
symptoms in adults with SAR (seasonal AR)1-3

1. FokkensW et al. Allergy 2007;62:1078–1084

2. Kaiser HB et al. J Allergy Clin Immunol 2007;119:1430–1437
3. Jacobs R et al. CurrMed Res Opin 2009;25:1393–1401
Significant and consistent improvement of ocular
symptoms in adults with SAR1,2

1. Kaiser HB et al. J Allergy Clin Immunol 2007;119:1430–1437

2. Jacobs R et al. CurrMed Res Opin 2009;25:1393–1401
 Consistency of ocular
Efficacy in SAR across Intranasal corticosteroids
Inconclusive/negative Clinical benefit/positive

100

80

60

40
Studies %

20

-20

-40

-60

-80

-100

Consistent ocular efficacy in rhinitis allergy

1. Keith P and Scadding GK. Curr Med Res Opin 2009;25:2021–41; Keith P and Scadding GK
Erratum. Curr Med Res Opin 2010: 26: 177.
Fluticasone furoate: ocular effect

• Multifactorial: Naso-ocular axon reflex

– Reduce mast cells 1. Fluticasone furoate
has enhanced

– Reduce nasal IgE affinity for the

glucocorticoid
receptor1
– Reduce eosinophils
– Improve nasal epithelial 2. This may
produce
integrity to reduce a greater
inhibitory effect
allergen absorption on the
naso-ocular
reflex mechanism
– Reduce eosinophil
progenitors 3. The release of
mediators that
cause ocular
– Reduce nasal ocular symptoms is
reduced

reflex

1. Adapted from Scadding GK and Keith PK. Expert Opin Pharmacother 2008;9:2707–15.
2. Naclerio R. Otolaryngol Head Neck Surg 2008;138:129–39.
Consistent efficacy in seven individual nasal and
ocular symptoms with SAR1
Integrated analysis from 4 studies; treatment period 14 days

Avamys is a distinct drug molecule and not a salt or a pro-drug of fluticasone2

1. Maspero J et al. Allergy Asthma Proc. 2010;31:483-92

Integrated analysis in adults with PAR1

1. Wu W et al. Allergy Asthma Proc 2013;34:283-91

Integrated analysis in adults with PAR1

1. Wu W et al. Allergy Asthma Proc 2013;34:283-91

Long term efficacy in PAR1

1. Rosenblut A et al. Allergy 2007;62:1071-1077

FFNS improves health-related QoL
In adults with SAR (European Grass study)

Non-nose Practical Nose Eye Emotional

Overall Activities Sleep symptoms problems symptoms symptoms problems
Change from baseline in

–0.5
RQLQ score

–1

–1.5

–2 *
** * **
–2.5 **
FFNS 110 µg
** ** ** Placebo
–3

**P=0.001; *P<0.05

1. Jacobs R et al. Curr Med Res Opin 2009;25:1393–1401

FFNS improves health-related QoL
In adults with PAR

Non-nose Practical Nose Eye Emotional

Overall Activities Sleep symptoms problems symptoms symptoms problems
0
Change from baseline in

–0.5
RQLQ score

–1

–1.5
* *

–2 *
* *
FFNS 110 µg
Placebo
–2.5 * * *
*P<0.001

1. Vasar M et al. Allergy Asthma Proc 2008;29:313–21

Side effects of intranasal steroids1,2

• The most common local adverse events (AEs) are:

– Epistaxis
– Throat irritation and nasal dryness
– Burning
– Stinging
– Nasal ulceration

1. Sastre J and Mosges R. J Investig Allergol Clin Immunol 2012;22:1-12

2. Fluticasone furoate (intranasal formulation). GDS v10. 14th April 2015
Avamys is not associated with an increased
incidence of ocular AEs1
There was no difference between Avamys and placebo on ocular safety in patients ≥12 years after 2 years of
continuous treatment

1. Laforce C et al. Ann Allergy Asthma Immunol 2013:111:45-50

Long term safety of Avamys: Incidence of ocular
AEs1

1. Rosenblut A et al. Allergy 2007;62:1071-1077

Serum cortisol levels in adults
Serum cortisol weighted mean (ratio from baseline)

Least square mean

Treatment Treatment
95% CI
comparison ratio
Active Placebo

FFNS 110 µg vs
0.97 0.99 0.98 (0.89, 1.07)
placebo
Prednisone vs
0.49 0.99 0.49 (0.43, 0.57)
placebo

1. Patel D et al. Ann Allergy Asthma Immunol 2008;100:490–6

Nasal Biopsy

Baseline and After 12 months Treatment with FFNS

Following 12 months of treatment, there was greater reduction in sub-

epithelial inflammatory cell infiltration with FFNS as compared to MFNS.
Similar to MFNS, FFNS showed no evidence of mucosal atrophy.

1. Fokkens et al. Am J Rhinol Allergy. 2012 ;26(1):36-44

1 year growth velocity (cm/yr) measured by
stadiometry in paediatrics1
Avamys (110 μg) treatment over 52 weeks in pre-pubescent children resulted in a
0.27 cm reduction in growth velocity compared with placebo [95% CI -0.48 to -0.06]1

Subgroup Avamys Placebo

(n=217) (n=218)
Female, n 68 67

Baseline mean (SD) 6.08 (1.22) 6.16 (1.22)

Treatment mean (SD) 5.54 (1.44) 5.88 (1.19)

Change (SD) -0.54 (1.61) -0.28 (1.73)

Male, n 149 151

Baseline mean (SD) 5.87 (1.26) 5.89 (1.21)

Treatment mean (SD) 5.34 (1.05) 5.60 (1.24)

Change (SD) -0.53 (1.51) -0.29 (1.49)

The recommended starting dosage is a total daily dose of 55 μg. Patients not adequately responding may use total
daily dose, 110 μg and then reduce back to 55 μg once adequate control of symptoms is achieved2

1. Lee LA et al. J Allergy Clin Immunol Pract. 2014;2:421-7 Table adapted from Lee et al. 2014
2. Fluticasone furoate (intranasal formulation). GDS v10. 14th April 2015
Conclusion
Summary
• AR is a global burden
• AR significantly impacts patient quality of life
• Co-morbidities are highly prevalent with AR
• The presence of AR often precedes the development of asthma
• A number of treatment guidelines exist, with the ARIA guidelines being the most
robust
• ARIA recommend intranasal glucocorticosteroids for treatment of AR in adults
• Avamys is an effective and well tolerated treatment for adults and children with AR
Avamys abbreviated PI
QUALITATIVE AND QUANTITATIVE COMPOSITION AVAMYS Nasal Spray is a white, uniform suspension contained in an amber glass bottle, fitted with a metering (50
microlitres) atomising spray pump. Each spray of the suspension delivers approximately 27.5 micrograms of micronised fluticasone furoate as an ex-device dose. CLINICAL
PARTICULARS Indications Adults, Adolescents (12 years and over) and Children (6 – 11 years) AVAMYS is indicated for the treatment of: the symptoms of allergic
rhinitis. DOSAGE AND ADMINISTRATION Adults and Adolescents (12 years and older) The recommended starting dosage is 2 sprays (27.5 micrograms per spray) in
each nostril once daily (total daily dose, 110 micrograms). Once adequate control of symptoms is achieved dose reduction to 1 spray in each nostril once daily (total daily
dose, 55 micrograms) may be effective for maintenance. The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. Children (6-11
years) The recommended starting dosage is 1 spray (27.5 micrograms per spray) in each nostril once daily (total daily dose, 55 micrograms). Patients not adequately
responding to 1 spray in each nostril once daily (total daily dose, 55 micrograms) may use 2 sprays in each nostril once daily (total daily dose, 110 micrograms). Once
adequate control of symptoms is achieved dose reduction to 1 spray in each nostril once daily (total daily dose, 55 micrograms) is recommended. Children (under 6 years
of age) The experience in children under the age of 6 years is limited. Safety and efficacy in this group has not been well established. Elderly No dosage adjustment
required. Renal impairment No dosage adjustment required. Hepatic impairment No dosage adjustment is required in patients with mild to moderate hepatic impairment.
CONTRAINDICATIONS AVAMYS Nasal Spray is contra-indicated in patients with hypersensitivity to any of the ingredients. WARNINGS AND PRECAUTIONS AVAMYS
Nasal Spray undergoes extensive first-pass metabolism by the liver enzyme CYP3A4, therefore the pharmacokinetics of intranasal fluticasone furoate in patients with severe
liver disease may be altered. Based on data with another glucocorticoid metabolised by CYP3A4, co-administration with ritonavir is not recommended because of the
potential risk of increased systemic exposure to fluticasone furoate. INTERACTIONS Fluticasone furoate is rapidly cleared by extensive first pass metabolism mediated by
the cytochrome P450 3A4. PREGNANCY AND LACTATION Adequate data are not available regarding the use of AVAMYS Nasal Spray during pregnancy and lactation in
humans. AVAMYS Nasal Spray should be used in pregnancy only if the benefits to the mother outweigh the potential risks to the foetus. FERTILITY There are no data in
humans. PREGNANCY Following intranasal administration of AVAMYS Nasal Spray at the maximum recommended human dose (110 micrograms/day), plasma fluticasone
furoate concentrations were typically non-quantifiable and therefore potential for reproductive toxicity is expected to be very low. LACTATION The excretion of fluticasone
furoate into human breast milk has not been investigated. Administration of fluticasone furoate to women who are breastfeeding should only be considered if the expected
benefit to the mother is greater than any possible risk to the child. EFFECTS ON ABILITY TO DRIVE AND USE MACHINES Based on the pharmacology of fluticasone
furoate and other intranasally administered steroids, there is no reason to expect an effect on ability to drive or to operate machinery with AVAMYS Nasal Spray.
OVERDOSE Symptoms and Signs In a bioavailability study, intranasal doses of up to 24 times the recommended daily adult dose were studied over three days with no
adverse systemic effects observed. TREATMENT Acute overdose is unlikely to require any therapy other than observation. REFERENCES 1. Berger WE, et al. Intranasal
corticosteroids: the development of a drug delivery device for fluticasone furoate as a potential step toward improved compliance. 2007; 4(6): 689-701. 2. Pharmaceutical &
Medical Packaging News. May 2008. Vol 16, no. 5 3. PI BPOM Approved 04 May 2015
 Thank You!
Menara Standard Chartered 35th Fl.
Jl. Prof Dr Satrio No. 164, Jakarta 12930
Ph: +62 21 2553 2350 Fax: +62 21 2553 2355
Before prescribing, please consult to PI (Prescribing Information) available on request
Adverse Events should be reported to GlaxoSmithKline Indonesia
by phone 08118438228 or email to yqq68540@gsk.com

For Health Care Professional only

ID/ALG/0002/17 AD: XX/XX/2017 ED: XX/XX/2019