1. Bulgaria Ewopharma MedReps Training Course 14 December 2010

2. Agenda 8.30-10.00 am Who is the allergic patient ?
How the allergic patient is managed ?
Why the allergic patient is underdiagnosed ?
Why the allergic patient is undertreated ?
Break
10.15 – am
Grass rationalisation,
Posology - arguments to increase to 8 drops per day
Patient follow up,
Post graduate course presentation and arguments

3. Allergic patient: the current practice
Who is the allergic patient ?
How the allergic patient is managed ?
Why the allergic patient is underdiagnosed ?
Why the allergic patient is undertreated ?

4. Who is the allergic patient ?
Epidemiology of respiratory allergic diseases
ECHRS
ISAAC
Classification of respiratory allergic diseases
ARIA
GINA
The natural course of allergic diseases

5. Allergic Rhinitis: prevalence in Europe
Prevalence of AR in a population-based survey in 6 EU countries1:
UK, Germany, France, Belgium, Italy and Spain
AR European prevalence is 23%, of which 45% are undiagnosed1
26.0%1
29.8%2
500 million people suffer from AR worlwide
20.6%1
21.0%3
24.5%1
16.9%1
AR prevalence is quite high, with almost half of sufferers not being diagnosed.
From those, a percentage have severe uncontrolled symptoms (target population for AIT).
21.5%1
1.Bauchau V., Durham S.R., Eur Respir J 2004:
2.Bachert C. Allergy 2006: 61:
3.Brehl P. Ind Health 2003 Apr; 41 (2): 121-3

6. Masoli et al. Allergy 2004; 59(5): 469-78.
Prevalence of clinical asthma in both adults and children : ISAAC Study
Proportion of population (%)
10.1
2.5–5.0
7.6–10.0
0–2.5
5.1–7.5
No standardised data
Masoli et al. Allergy 2004; 59(5):

7. What is a severe allergic rhinitis ?
Classification of allergic rhinitis*:
New classification developed in 2001 by the ARIA consensus (Allergic
Rhinitis and its Impact on Asthma) in order to characterise rhinitis and its
impact on the quality of life according to its duration (intermittent or
persistent) and the severity of the symptoms. 
*Bousquet J. et al. Allergic Rhinitis and its Impact on Asthma (ARIA).Allergy 2008: 63 (Suppl. 86): 8–160
Intermittent
Symptoms
< 4 days per week
or < 4 weeks
Persistent
> 4 days per week
and > 4 weeks
Slight
• normal sleep
• normal social and leisure activities
• normal work and school life
• symptoms causing minimal discomfort
Moderate - Severe
• sleep disturbed
• disrupted social and leisure activities
• disrupted work and school life
• unpleasant symptoms

8. Profile of patients consulting the allergist
REALIS survey:
clinical and sensitization profile of patients consulting for respiratory allergies in France
80.3%
moderate to severe patients
N=2714
Allergists and pulmonologists recruited patients consulting for respiratory allergy and who were being tested for allergy for the first time (September January 2008)
The severity of allergic rhinitis or asthma was assessed by ARIA 2001 and GINA 2006 guidelines
Among patients who were seen by a specialist, the majority (more than 8 in 10) had moderate to severe AR.
~ 80% of AR patients consulting an allergist have moderate-to-severe symptoms
They have had allergic rhinitis symptoms during 4 to 5 years before they look for an allergy specialist
M.Migueres et al. French REALIS survey. Abstract at XXVIII EAACI

9. Altered quality of life due to the allergic symptoms
SLEEP & TIREDNESS
77 % of patients had sleep troubles
46 % of patients felt tired
DAILY ACTIVITIES IMPAIRED
LEARNING & COGNITIVE FUNCTIONS DISTURBED
Impact on Allergic Respiratory Diseases
WORK & SCHOOL PRODUCTIVITY
< 90 % effectiveness at work
< 93 % impaired classroom performance
EMBARRASSMENT
Adolescents embarassed to use inhalers

10. Allergic rhinitis is a risk factor for asthma
WHO – Initiative ALLERGIC RHINITIS AND ITS IMPACT ON ASTHMA (ARIA)
Allergic rhinitis has been defined by the WHO as major chronic disease of the airways
Allergic rhinitis is a risk factor for asthma
Expand the diagnosis: think of rhinitis in patients with asthma, think of asthma in patients with rhinitis
WHO – Initiative 2000: Ein aktuelles Dokument der Weltgesundheitsorganisation WHO mit dem Titel „ALLERGIC RHINITIS AND IT´S IMPACT ON ASTHMA (ARIA)“ weist auf die enge Bezeihung zwischen einer Allergie an der Nase und der Lunge hin und fordert eine gemeinsame Behandlungsstrategie für beide Organsysteme.
A common treatment strategy for rhinitis and asthma patients is recommended!

11. Why the allergic patient is underdiagnosed ?
How the allergy diagnosis must be performed ?
How the GPs diagnose the allergic diseases ?
What’s going wrong with the allergy diagnosis ?

12. Diagnosis Process in Allergology
Patient with suspected respiratory allergy symptoms
Clinical history for allergy
Allergy testing
In allergy medicine, the diagnostic process itself is relatively simple but does need to follow a specific sequence. Firstly, one has to draw up a detailed medical profile of the patient on the basis of his or her clinical history and a detailed interview. This will enable the practitioner to broadly identify the allergen or group of allergens that are most likely to cause the patient's symptoms.
During the patient interview, the practitioner seeks to establish the individual's personal medical history. Did he or she suffer from asthma or rhinitis as a child? And how about atopic dermatitis (an aggravating factor for the appearance of allergy)? In childhood, did the patient suffered from hypersensitivity to known allergenic foods?
The second phase will then involve specific allergen testing.

13. Skin prick-tests method
Allergens
Stallerpoint®

14. Measurement of the skin reaction 15 – 20 minutes after testing
Wheal diameter

15. How the GPs diagnose the allergic diseases ?
Patient with suspected respiratory allergy symptoms
Clinical history for allergy
Stop
In allergy medicine, the diagnostic process itself is relatively simple but does need to follow a specific sequence. Firstly, one has to draw up a detailed medical profile of the patient on the basis of his or her clinical history and a detailed interview. This will enable the practitioner to broadly identify the allergen or group of allergens that are most likely to cause the patient's symptoms.
During the patient interview, the practitioner seeks to establish the individual's personal medical history. Did he or she suffer from asthma or rhinitis as a child? And how about atopic dermatitis (an aggravating factor for the appearance of allergy)? In childhood, did the patient suffered from hypersensitivity to known allergenic foods?
The second phase will then involve specific allergen testing.

16. Why the allergic patient is underdiagnosed ?
What’s going wrong with the allergy diagnosis ?

17. Consultation is not frequent
“How recently have you been seen by a health care professional?”
-Internet and telephone survey conducted in 2005 in general population from UK, Germany, Italy and Spain
-N=2966 randomly selected adults with allergies
Despite a high number of European population suffering from allergy, the consultation is not frequent.
~10% of the European population with rhinitis symptoms was never seen by a health care professional (nurse or doctor) for their condition
Maurer M, Zuberbier T, Allergy 2007: 62:

18. 19% have consulted a specialist
Only 1 patient over 5 consulted a specialist
TNS STUDY:
TNS survey conducted in France N= 623 subjects with AR symptoms from 2003 general
population
TYPE OF DOCTORS CONSULTED BY PATIENTS:
19% have consulted a specialist
*Several consultations per doctor were possible
**in France, a first consultation with a GP is mandatory before referral to a specialist
When patients consult a doctor, the majority sees a GP. Only one patient in 5 consult a specialist.
It is important to note that in France a patient must first be seen by a GP, who then decides if the patient should be referred to a specialist. In
94% of patients consulting a GP in 1st line treatment
19% consulted a specialist (13% an allergist**), in 2nd line treatment
A.Didier et al. Unmet therapeutic needs in AR. Abstract at XXIX EAACI 2010

19. How the allergic patient is managed ?
The allergen avoidance
The pharmacotherapy
The allergen immunotherapy (AIT)

20. The optimal management of the allergic patient
The patient education
Allergen avoidance
Allergen Immunotherapy
Pharmacotherapy

21. Why the allergic patient is undertreated ?
The efficacy of the allergen avoidance ?

22. Allergen avoidance : recommended but a limited efficacy
Mites: efficacy not well demonstrated
Animals : patients can be sensitized without direct contact with pets
Pollen: Unfeasible

23. Why the allergic patient is undertreated ?
The efficacy of the pharmacotherapy ?

24. Therapy of Allergic Rhinitis
ARIA Update 2007
WHO
Intermittent symptoms
Persistent symptoms
Mild
intermittent
Severe
intermittent
Mild
persistent
Severe
persistent
Severity of Allergic Rhinitis patients
Allergen and irritant avoidance
Oral or local non-sedative H1-blocker
Intra-nasal or oral decongestant
Intranasal steroid
Local cromone
Specific Immunotherapy
11 % % % %

25. Current Symptomatic Treatments
Rhinitis
H1-Antihistamines
Inhaled corticosteroids
B2-agonists & Bronchodilators
Antileucotriens
Nasal corticosteroids
Rhinitis
Asthma
Rhinitis
Asthma
Asthma

26. Total rhinitis score: Nasal Mometasone%
MFNS 100mcg/QD
MFNS 200mcg/QD 79
Placebo 75 75 71 70 63 59 60 53 53 44 45
Mean improvement from baseline 36 34 29
Slide 21: Safety and tolerability of grass pollen tablet sublingual immunotherapy
The oral mucosa contains a limited number of proinflammatory cells, such as mast cells, which probably contributes to the absence of anaphylactic reactions with sublingual immunotherapy the basis of the therapy’s excellent safety profile.
In this study all treatment doses were well-tolerated and as in previous studies of sublingual immunotherapy there were few serious and no fatal adverse events. The slide shows the treatment-emergent adverse events with an incidence of more than 5% in the safety population. These were almost all local reactions related to direct oral contact with the allergen and mainly occurred at the beginning of the treatment course during the initiation phase. They were seen rarely or were absent from the placebo treated group. All local reactions resolved without medical intervention. Other frequently reported adverse events were headache and nasopharyngitis the incidence of which was similar across all treatment groups including the placebo group. Can we say something about formulation or adjuvants improvements underway here to reduce these AEs?
The number of patients reporting “severe” AEs was similar in each of the active treatment groups, 10 for 100 IR and 500 IR and 8 for 300 IR. Not all patients experiencing severe adverse events left the study, only 3 withdrew from the 100 IR, 6 from the 300 IR and 8 from the 500 IR. No patients withdrew from the placebo group because of treatment-emergent adverse events. One patient in the 300 IR group and two in the 500 IR group experienced serious adverse events but these were not related to the study medication.
Time (day)
* p0.01 relative to placebo
Van Drunen et al., Allergy 2005: 60 (Suppl. 80): 5-19

27. Total rhinitis score : Nasal Mometasone
MFNS 50mcg/QD
MFNS 100mcg/QD 60
MFNS 200mcg/QD
MFNS 800mcg/QD
Placebo 50 40
Improvement in total nasal symptom scores 30 20 10
Baseline 3 7 14 21 28
Endpoint
Time (day)
Van Drunen et al., Allergy 2005; 60 (Suppl. 80): 5-19

28. Rhinitis symptoms in seasonal AR Montelukast vs. placebo and Loratadin
Daytime nasal symptoms
Daily composite (daytime nasal & night-time)
Night-time symptoms
-0.6
-0.5
-0.4
-0.3
-0.2
-0.1
-9%
-16%
-22%
-8%
-20%
-15%
-9%
-16%
-20%
Change from baseline (0-3 scale; LS mean  SE)
Placebo
Montelukast
Loratadine
Philip et al., Clin Exp Allergy 2002; 32:

29. A patient uncontrolled and not satisfied by the pharmacotherapy
35-40 % of patients receiving optimal standard symptomatic treatment experience poor symptom control
The level of patient dissatisfaction are high with these medications

30. What are the unmet needs ?
Patient satisfaction / perception
Patient expectation: a long term efficacy

31. What are the unmet needs ?
Patient satisfaction / perception

32. Allergic Rhinitis Management
Good
100%
Medium
Bad
75%
50%
25% 0%
Nasal corticosteroid
regular
regular
intermittent
intermittent
Anti-histamine
regular
intermittent
regular
intermittent
How do patients feel after their symptomatic treatment (anti H1, corticosteroid) ?
White et al. , Clin Exp Allergy1998

33. everybody knows this word.
The paradox of allergy
„Allergy“
everybody knows this word.
Only 10 per cent of
allergic patients are
treated correctly.

34. symptomatic treatments 48 % have bad quality of life
Allergic Rhinitis and unmet therapeutic needs
TNS 2009: 623 subjects with AR/ 2003 individuals from general population
Control with
symptomatic treatments
Quality of life
Three quarters of patients who have consulted a doctor within the last 12 months remain uncontrolled despite the use of symptomatic treatments.
Half of those uncontrolled patients have a bad quality of life.
73% remain uncontrolled
(19% of total population)
48 % have bad quality of life
(13% of total population)
19% of allergic rhinitis patients remain uncontrolled and 13% have a poor quality of life despite using symptomatic treatments
A.Didier et al. Unmet therapeutic needs in allergic patients . Abstract at XXIX EAACI 2010

35. Unsatisfied needs Symptomatic treatment Social and financial impact
No long term efficacy
No effect on the disease modifying
Lack of compliance
Dissatisfaction
Social and financial impact
Cost of the disease
Quality of life decrease
Chronicity of the disease
Resignation

36. What are the unmet needs ?
Patient expectation: a long term efficacy

37. Why AIT can satisfy the unmet needs ?
Immunomodulatory effect
Long term and sustained effect

38. Definition
Specific immunotherapy is the repeated administration of allergen products to allergic subjects to activate immunomodulatory mechanisms and provide sustained relief of symptoms during subsequent natural allergen exposure
WHO Guideline 1998
EMEA Guideline 2008

39. Immunomodulatory effect of AIT
Natural exposure
to the allergen
Lymphocytes B
IgE
IL- 4
CPA
Th2
Lymphocytes T
Mastocytes
AIT
Allergy
T reg
Lymphocytes T regulator

40. Recruitment and activation of mast cells and eosinophils
Allergen Immunotherapy: from the immunological effects to the symptomatic effect
Recruitment and activation of
mast cells and eosinophils
Nasal, ocular and bronchial
hyperreactivity
AIT
decrease
Symptoms
Use of antiallergic drugs

41. Allergen Immunotherapy
AIT is the only treatment that modifies the natural evolution of allergy
One
allergy
Two allergies
Several
allergies
Allergen Immunotherapy
Allergic Asthma
Allergic Rhinitis

42. Why the allergist is the expert ?
Diagnosis
AIT indications
Patient management and follow-up

43. Diagnostic Approach In Allergology
Allergy History
Skin Tests/
IgE
Symptoms Moderate/severe
Poor QOL
Positive

44. AIT Indication Pathway
Allergy History
Skin Tests/
IgE
Symptoms Moderate/severe
Poor QOL D I
AGNOS S
Positive
Indication for AIT ?
Contra indications:
Immunoptahologic diseases
Severe asthma
- Malignancy
- Treatment withβ-blockers
- Chronic mouth disease
- Pregnancy: avoid initiaition of immunotherapy during pregnancy NO
YES
Age ≥ 4 yrs old
SLIT with pollens mixtures or 2 non related allergens
SLIT with one allergen

45. Which Allergen for AIT ? Monosensitization Polysensitization
A patient with moderate/severe symptoms during/after allergen exposure
A patient with an altered quality of life due to the allergic symptoms
A patient not improved and not satisfied by the pharmacotherapy
A patient accurately diagnosed
For allergic respiratory diseases
Monosensitization
Polysensitization

46. What are the key success factors for AIT ?
Patient Information
Patient’s Action Plan
Patient Follow-Up
Patient
Doctor
Relationship

47. Key success factors for AIT Patient information = Patient Education
Patient should understand :
His/her allergic disease
The goals of SIT
The disease modifyer effect of SIT
Why 3-5 years of SLIT ?
The onset of action of SLIT
The importance of compliance for the success of SLIT

48. BREAK
15 minutes

49. Agenda 10.15 – 12.30 am Grass rationalisation
Posology - arguments to increase to 8 drops per day
Patient follow up
Post graduate course: presentation and arguments

50. Grass rationalisation
5 Grasses / 4 cereals mixture: is it still relevant ?
High level of allergens cross-reactivity between 5 grasses and cereals
5 grasses alone is sufficient to treat the allergic patient sensitized to grass pollen and cereal pollen.

51. Rationale to increase to 8 drops per day

52. STALORAL pollen: The optimal posology
Currently:STALORAL 4 press/day = 120 IR/day
ORALAIR clinical trial:
100 IR/day = No efficacy
300 IR/day = Efficacy
STALORAL 8 press/day = 240 IR/day
STALORAL 10 press/day = 300 IR/day ?

53. Minimal Maintenance dose:
SLIT - pollen
Pollen season
1st year
Pre-seasonal IT
Co-seasonal
Withdraw
SLIT
for 6 months
3 – 4 MONTHS
2 Months
Minimal Maintenance dose:
300 IR / 4 press/day
Initial phase
9-11 days
Maintenance phase
5 – 6 months

54. Patient follow up

55. Patient Information/Communication Give the right message to the patient !!
“Allergy is a chronic disease not curable by pharmacotherapy alone..”
“Rhinitis will develop into asthma in 50 % of the patients..”
“You may develop new allergic sensitizations..”
“The only way to affect the disease is by immune intervention..”
“ SIT is a three years treatment but compared to lifelong drug intake..”
“ Efficacy of SIT persists longtime after cessation “
“ SIT would positivily affect your quality of life…”

56. Key success factors for SIT Patient Information/Education needs from the doctor
Time
Conviction / Enthousiasm/Persuasion
To be done at regular intervals (not a one shot issue)

57. Patient compliance: a major issue
Factors of non-compliance :
Daily intake
Treatment duration: 3-5 years

58. Key success factors for AIT Patient compliance: a major issue
Patient Follow-Up
Optimal patient follow-up
SIT efficacy assessment

59. An optimal follow-up for a patient treated with perennial SLIT
Build-up
maintenance (Year 1) 5 visits
Start
Visit
Visit
Visit
Visit
Visit
12th month
1st month
3rd month
6th month
9th month
Go/No Go
maintenance (Year 2) 3 visits
Visit
Visit
Visit
16th month
20th month
24th month
maintenance (Year 3) 3 visits
Visit
Visit
Visit
28th month
32th month
36th month
Stop

60. An optimal follow-up for a patient treated with seasonal SLIT
Build-Up
maintenance (année 1) 3 visits
Start
Go/No Go
Visit
Visit
Visit
Pollen season
3-4 months post-season
3-4 months before
season
maintenance (Year 2) 3 visits
Build-Up
Pollen season
3-4 months post-season
3-4 months before
season
maintenance (Year 3) 3 visits
Build-Up
Pollen season
3-4 months post-season
3-4 months before
season
STOP

61. Content of follow-up visits
One month
after starting
3 months
6 months
9 months
12 months
Safety
Staloral intake
Safety
Staloral intake
Compliance
Compliance
Efficacy
Compliance
Satisfaction
Efficacy
Compliance
Satisfaction
Efficacy
Willingness to continue

62. SIT efficacy assessment is based only the clinical parameters
Reduction of symptoms
Rhinitis
Conjunctivitis
Asthma
Reduction of anti-allergic drugs intake
Improvement of Quality of life
Compliance
Satisfaction
Efficacy
Willingness to continue

63. Efficacy Assessment using a color-coded VAS (1/3)
Symptoms :
Before SLIT
Good Average Bad
How was your daytime rhinitis
condition ?
How was your nighttime rhinitis
condition ?
How was your daytime asthma
condition ?
How was your nighttime asthma
condition ?
Green
area
Orange
area
Red
area

64. Efficacy Assessment using a color-coded VAS ((2/3)
Symptoms
6 months later
Good Average Bad
How was your daytime rhinitis
condition ?
How was your nighttime rhinitis
condition ?
How was your daytime asthma
condition ?
How was your nighttime asthma
condition ?
Green
area
Orange
area
Red
area

65. Efficacy Assessment using a color-coded VAS (3/3)
Symptoms
12 months later
Good Average Bad
How was your daytime rhinitis
condition ?
How was your nighttime rhinitis
condition ?
How was your daytime asthma
condition ?
How was your nighttime asthma
condition ?
Green
area
Orange
area
Red
area

66. Rescue Medication for allergic rhinitis
Efficacy Assessment ?
Rescue Medication for allergic rhinitis
H1-Antihistamine
Nasal Steroids %
100
- 25%
- 50 % 50 - J0
9 M
12 M
Months

67. Rescue Medication for allergic asthma
Efficacy Assessment ?
Rescue Medication for allergic asthma
β2-agonists
Inhaled Steroids %
100
- 25%
- 50 % 50 - J0
9 M
12 M
Months

68. Items Quality of life Efficacy Assessment ? SLEEP & TIREDNESS
DAILY ACTIVITIES IMPAIRED (sport, work, school)
WORK & SCHOOL PRODUCTIVITY
LEARNING & COGNITIVE FUNCTIONS DISTURBED

69. After 12 months of SIT: Efficacy assessment%
≥ 50 %
Months
At least 50 % reduction of symptoms and rescue medicaction use and a significant QOL improvement should be achieved at 12 months

70. After 36 months of SIT: Stop & Follow-Up
≥ 50 % %
≥ 80 %
Stop
and follow-up
Months
At least 80 % reduction of symptoms and rescue medicaction use and a significant QOL improvement should be achieved at 36 months

71. SIT efficacy assessment
≥ 50 % %
≥ 80 %
SIT Stop
Month

72. Sustained long term efficacy of SIT
≥ 80 %
SIT
Stop
Month
Years

73. Add one or two additionals years if necessary
≥ 50 % %
Months

74. Post - SIT : Patient follow-up
year
2nd
year
3rd
year
4th
year
5th
year
A visit once a year

75. After 12 months of SIT: a key milestones
STOP ? Symptoms weakly improved No change in rescue medications QOL not improved Compliance poor Safety average / bad Patient/parent not satisfied

76. After 12 months of SIT: Why to stop ?%
Months
Less than 50 % reduction of symptoms and rescue medicaction use and a poor QOL improvement have been achieved at 12 months

77. After 12 months of SIT: a key milestones
Before taking the decision to Stop, Check:
Compliance :
vials renewal; missing periods : changes in personal or familial conditions , cost issue, willingness to pursue the treatment
Environmental changes:
increase in allergenic load/ Co-factors irritant
Co-morbidities :
not treated
If none of these factors are found, go-back to the diagnosis and recheck the indications

78. Key Message
To be successful SLIT needs: A good indication The best candidate An optimal patient management

79. Post graduate course presentation and arguments
Objectives
Contents
Organisation

80. Post graduate course presentation and arguments (1)
STALLERGENES
Post Graduate Course
An Essential Half-Day Training Course On :
Sublingual Immunotherapy in Practice

81. Post graduate course What The Course Will Cover ?
A stepwise approach for the indications of SLIT
The place of SLIT in the treatment of allergic respiratory diseases
The key factors to make SLIT a success
The compliance/adherence issue and how to tackle it

82. Post graduate course : the agenda
Welcome – Introduction 15’
The basics of SLIT : recall 15’
Workshop 1 : Choosing the right patient for SLIT 60’
Coffee Break ’
Workshop 2 : Managing the patient optimally 60’
The patient follow-up handbook 15’
Interactive Quizz ’
Take-home messages ’
3 hours 30 duration

83. Post graduate course Who Should Attend ?
Allergists
Experience with SLIT: at least 1 year
10 to 15 attendees/ session

84. Post graduate course : Meeting Date 2011
March 2011
Varna
Plovdiv
Sofia