1. Practical aspects Of SLIT
Giovanni Passalacqua
Allergy & Respiratory Diseases
Dept.Internal Medicine-
University of Genoa ITALY

2. SLIT Trials in Guidelines
1998
2001
2007
2008
2009
WHO Pos pap
EAACI Pos Pap
ARIA 1st version
Galen Update
ARIA 2nd version
WAO Pos pap
TODAY 4 5 8 22 35 60 66

3. WHO Pos Pap. Therapeutical vaccines for allergic diseases
Allergy 1998
Standards for practical
allergen-specific
immunotherapy.
Allergy 2006
Allergen immunotherapy: A practice parameter second update
JACI 2007

4. Passalacqua G Allergy Immunol Clin North Am 2011

5. Meta-analysis of the efficacy of sublingual immunotherapy in allergic asthma in pediatric patients, 3 to 18 years of age.
M Penagos, G Passalacqua, E Compalati, C Baena-Cagnani, S Orozco, A Pedroza GW Canonica

6. Allergy 2011

7. Symptom
Score
Rhintis

8. JACI 2010

9. HOW DO WE
MANAGE SLIT
HOW DO
PATIENTS
MANAGE SLIT ?

10. RHINITIS HIGH RISK? ASTHMA
Indications
Moderate-
severe
persistent
Not cost-
effective?
Mild
persistent
RHINITIS
Moderate-
severe
intermitt.
Mild
intermitt.
IMMUNOTHERAPY.
HIGH
RISK?
ASTHMA
Intermitt.
Mild
Moderate
Severe

11. FACTORS TO BE CONSIDERED IN PRESCRIBING IMMUNOTHERAPY
IgE-mediated mechanism
Confirmed aetiological role of the allergen
Duration of symptoms
Response to drug therapy
Expected effectiveness
Availability of standardized vaccines
Contraindications and risks
Costs
Compliance
WHO Pos Pap 1998

12. CAUSAL ROLE OF THE ALLERGEN(S):
Clinical history and exposure
SKIN TESTING
RAST ASSAY
NASAL (CONJUNCTIVAL)
CHALLENGE
SLIT (IT in general) for the clinically relevant allergen(s)
Preferably one, but in selected cases 2 or 3 extracts.

13. Subcutaneous (SCIT)
Sublingual (SLIT)
ADMINISTRATION
Standard
Rush
Ultra-rush
Cluster
No build-up (SLIT)
BUILD-UP
Monthly (SCIT)
Once a day (SLIT)
Each other day (SLIT)
Once a week
TIMING
Preseasonal
Pre-coseasonal
Co-seasonal
Continuous
REGIMEN

14. SLIT NO BUILD UP 7/60 MAINTENANCE DAILY 31/60 MAINTENANCE 3/wk 20/60
NO BUILD UP
7/60
MAINTENANCE DAILY
31/60
MAINTENANCE 3/wk
20/60
MAINTENANCE 2/wk
MAINTENANCE 1/wk
2/60
POLLEN CONTINUOUS
8/43
POLLEN PRESEASONAL
3/43
POLLEN COSEASONAL
POLLEN PRECOSEASONAL
29/43
Lombardi et al, Allegy 2009

15. SLIT 31/60 (1 negative) 20/60 (1 negative) 7/60 (1 negative)
NO BUILD UP
7/60
MAINTENANCE DAILY
31/60 (1 negative)
MAINTENANCE 3/wk
20/60 (1 negative)
MAINTENANCE 2/wk
7/60 (1 negative)
MAINTENANCE 1/wk
2/60 (1 negative)
POLLEN CONTINUOUS
8/43
POLLEN PRESEASONAL
3/43
POLLEN COSEASONAL
POLLEN PRECOSEASONAL
29/43
Lombardi et al, Allegy 2009

16. SLIT POLLEN CONTINUOUS 8/43 POLLEN PRESEASONAL 3/43 POLLEN COSEASONAL
NO BUILD UP
7/60
MAINTENANCE DAILY
31/60
MAINTENANCE 3/wk
20/60
MAINTENANCE 2/wk
MAINTENANCE 1/wk
2/60
POLLEN CONTINUOUS
8/43
POLLEN PRESEASONAL
3/43
POLLEN COSEASONAL
POLLEN PRECOSEASONAL
29/43
Lombardi et al, Allegy 2009

17. SLIT: Key-points
Follow manufacturers’ instructions
For seasonal allergies the pre-coseasonal regimen seems to be the best choice
The build-up phase is not necessary and an be omitted
The once daily administration is usually more convenient and easy to do.

18. ADHERENCE:
The literature
Curr Opin Allergy Clin Immunol 2009

21. 1 visit/year
2 visit/year
3 visit/year

23. GRADING SIDE EFFECTS OF SUBLINGUAL IMMUNOTHERAPY SPEAKING THE SAME LANGUAGE
G.Passalacqua, CE Baena-Cagnani, J. Bousquet, GW Canonica, T. Casale, L.Cox, S.Durham, D. Larenas-Linnemann, RF Lockey, R. Pawankar, P.Potter, N. Rosario, D. Wallace, D. Ledford
IN PREPARATION
Symptom/sign
(see Table 1)
Grade 1 – Mild
Grade 2 – Moderate
Grade 3 - Severe
Unknown severity
Abdominal pain,
Diarrhea
Ear itching
Pruritus/swelling of mouth, tongue or lip
Nausea
Throat irritation
Uvular oedema
Vomiting
● Not troublesome
AND
● No symptomatic treatment required
● No discontinuation of SLIT because of local side effects
● Troublesome OR
● Requires symptomatic treatment
●No discontinuation of SLIT because of local side effects
·                     Grade 2 AND
·          SLIT discontinued because of local side effects
The treatment is discontinued but there is no subjective and/or objective description of the severity from the patient/physician
Each local adverse event can be early (<30 minutes) or delayed
WAO, in preparation

24. Anaphylaxis with SLIT Author, year Sex (age) Allergen (producer) Phase
Onset
Description
Epinephrine
De Groot, 2009
M (13)
Grass (Grazax, ALK-Abellò)
First dose
15 min
Generalized urticaria, swelling of tongue NO
F (27)
5 min
Abdominal cramps, asthma, generalized itching, hypotension
YES
Blazowski, 2008
F (16)
HDM (Staloral, Stallergenes)
Maintenance
overdose (60 drops)
10 min
Hypotension-collapse, flushing, urticaria
Eifan, 2008
F (11)
dust mite + grass pollen mix (Stallergenes)
Maintenance.
3 min
Abdominal pain, chest pain, fever, nausea
Not specified
Dunski, 2006
F (31)
Alternaria, cat, dog
grass, ragweed, (Greer)
2nd day of updosing
Angioedema, dizziness, dyspnea, generalized itching
Antico, 2006
F (36)
Latex
End of
rush buildup
Asthma, generalized urticaria

26. THE SAFETY OF SUBLINGUAL IMMUNOTHERAPY WITH ONE OR MORE ALLERGENS IN CHILDREN
Fabio Agostinis, Marcello Cottini, Carlo Lombardi, Giorgio Walter Canonica, Giovanni Passalacqua ,Allergy 2008 in press
SINGLE ALLERGEN n (%)
MULTI ALLERGENS n (%)
Grass
140 (82)
Grass + pariet
6 (2)
Parietaria
4 (3)
Grass+ olive
18 (7)
Birch
14 (9)
Grass + birch
+alder+hazelnut
220 (87)
Ragweed
Grass + ragweed
9 (4)
Olive -
Grass + mugwort
Birch+hazelnut
+alder
TOTAL
172 (100)
253 (100)
415 children, 3-18 years, 272 male

28. SIT IN ASTHMA: PROBLEMS
The majority of the trials were not designed and sized for asthma as primary outcome
Heterogeneity of study designs, duration, dose and evaluation parameters.
Few studies had functional parameters evaluated

29. SLIT: Key-points
Indications: the same as SCIT
Assess the causal role of the allergen
Safety: safer than SCIT (can be used cautiously also in children below 5 years)
Follow manufacturers’ instructions
Give the first dose under medical supervision
Carefully instruct patients on the possible side effects and their management
Check adherence (regular visits/phone calls)
Optimal duration 3-4 years