SUBLINGUAL IMMUNOTHERAPY
Giovanni Passalacqua
Allergy & Respiratory DiseasesAllergy & Respiratory DiseasesDept.Internal Medicine-Dept.Internal Medicine-
University of Genoa ITALYUniversity of Genoa ITALY
THE LITERATURE
66 RDBPC TRIALS
8 RANDOMIZED OPEN TRIALS
6 COMPARATIVE (SLIT vs SCIT)
6 TRIALS IN OTHER DISEASES
10
20
grass
HDM
parietaria
cypress
cat ragweed
birch
other
67%
Less or equal 6 months: 23 studies
Less or equal 12 months: 15 studies
More than 12 months: 20 studies
TREATMENT DURATION
< 20 : 4 studies
< 50 : 21 studies
< 100 : 16 studies
PATIENTS ENROLLED
< 150 : 11 studies
> 150 : 8 studies
10 STUDIES WITH SAMPLE SIZE CALCULATION
Durham 2006 De Blay, 2007Dahl 2006 Pfaar 2008Pham Ti 2007 Wahn 2009Roder 2006 Ott 2009Didier 2007 Bufe 2009Skoner 2010 Cortellini 2010
Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitisDurham SR, JACI 2006
Prolonged preseasonal treatment with Grazax improves the clinical efficacy
Calderon M et al, Allergy 2007
Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis.Dahl et al, JACI 2006
VERSUS PLACEBO:
SYMPTOM REDUCTION
- 30%MEDICATION REDUCTION
- 38%
634 PATIENTS !!!
VS PLACEBOSymptoms-28% (-39%)Medications- 24% (-48%)
Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis
Wahn 2009
VS PLACEBOSymptoms-34% to –44%
VS PLACEBOSymptoms -24% Medications - 34%
Sublingual immunotherapy for allergic rhinitis.Allergy, 2005. Wilson D., Torres Lima I, Durham S.
21 trials
Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients: Meta-analysis of randomized controlled trials.
Martin Penagos, Enrico Compalati, Francesco Tarantini, Rodrigo Baena Cagnani, Jose Huerta Lopez, Giovanni Passalacqua and Giorgio Walter Canonica
2006
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
SCIT SLIT
Clinical efficacy: Rhinitis Ia Ia
Clinical Efficacy: Asthma Ia Ia
Clinical efficacy: Children (rhinitis)Children (asthma)
IbIb
IaIa
Prevention of new sensitizations Ib IIa
Longterm effect Ib IIa
Prevention of asthma IIb IIb
ARIA Update on immunotherapySR Durham and G.PassalacquaJACI 2007 in press
Abramson 2003
Asthma A-C p< 0.01
Calamita 2006
Asthma A-C P= 0.07
Penagos 2008
Asthma C P= 0.02
Olaguibel 2005
Asthma/Rhinitis
C P= 0.01
Calderon 2007
Rhinitis A p< 0.01
Penagos 2006
Rhinitis C p= 0.02
Wilson 2005
Rhinitis A-C p= 0.002
A = adults C = children
Specific immunotherapy for respiratory allergy: state of the art according to current meta-analyses. Compalati E et al, Ann Allergy Asthma Immunol 2009
Meta analisi: sintomiSCIT
SCIT
SLIT
SLIT
SLIT
SLIT
SLIT
49 (OUT OF 60) RDBPC TRIALS SUITABLE FOR POOLING:2333 SLIT2256 PLACEBO
SYMPTOM SCORE
MEDICATION SCORE
SymptomScoreRhintis
JACI 2010
No fatal event reported since 1986
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
De Groot, 2009
F (27) Grass (Grazax, ALK-Abellò)
First dose 5 min Abdominal cramps, asthma, generalized itching, hypotension
YES
Blazowski, 2008
F (16) HDM (Staloral, Stallergenes)
Maintenanceoverdose (60 drops)
10 min Hypotension-collapse, flushing, urticaria
YES
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, doggrass, ragweed, (Greer)
2nd day of updosing
5 min Angioedema, dizziness, dyspnea, generalized itching
NO
Antico, 2006
F (36) Latex End of rush buildup
10 min Asthma, generalized urticaria
Not specified
Anaphylaxis with SLIT
Cox L, Linneman D, Nolte H, Weldon D, Finegold I, Nelson HS. Sublingual immunotherapy: A comprehensive review. J Allergy Clin Immunol 2006; 117: 1021-35
In 41 studies with information on the total number of AEs, 1047 adverse reactions in a total of 386,149 doses were identified (2.7 reactions/1,000 doses).
In 49 studies with information on the number of patients, the AEs were 529 per 4378 patients (12%).
In the trials that specified the severity of reaction, the occurrence of severe AE was 0.56 per 1,000 doses.
Overall, 14 serious AEs probably related to the treatment were found.
Author N pats Age range Follow-up
AE % ofpatients
AE/1,000 doses
Di Rienzo 268 2-15 years 3 years 3 % 0.1/1,000
Lombardi 198 > 14 years 3 years 7.5 % 0.5/1,000
Pajno 354 5-15 years 36 months 6 % 0.15/1,000
Agostinis 36 3-5 years 2 years 5 % 0.07/1,000
Di Rienzo 128 3-5 years 2 years 5. 6% 0.2/1,000
SLIT: POST MARKETING SURVEYS
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 4 (3) Grass + ragweed 9 (4)
Olive - Grass + mugwort
Birch+hazelnut+alder
TOTAL 172 (100) 253 (100)
415 children, 3-18 years, 272 male
Coseasonal SLIT reduces the development of asthma in children with allergic rhinitis.Novembre E. et al, JACI 2004
SLIT NO SLIT
37
8
26
18
NO ASTHMA
ASTHMA
79 childrenAllergic rhinitis onlyFollow-up: 3 yrs
PREVENTIVE EFFECTS OF SUBLINGUAL IMMUNOTHERAPY IN CHILDHOOD.
AN OPEN RANDOMIZED CONTROLLED STUDY
MAURIZIO MAROGNA MD1 , D.TOMASSETTI1, A. BERNASCONI1, F.COLOMBO1,ALESSANDRO MASSOLO BS2, A. DI RIENZO BUSINCO4, GIORGIO W CANONICA
MD3, GIOVANNI PASSALACQUA MD3 AND SALVATORE TRIPODI MD4
1 Pneumology Unit, Cuasso al Monte, Macchi Hospital Foundation, Varese
2 Department of Animal Biology, University of Pavia, Pavia3 Allergy & Respiratory Diseases,Department of Internal Medicine, Genoa University
4 Pediatric Allergy Unit, S. Pertini Hospital, Rome
AAAI 2008, 101: 261
Diary card
Visit
Skin test
MCh challenge
144 SLIT
72 CONTROLS
14 dropout
6 dropout
1 yearBASELINE
RANDOMIZED PHASE
Year 1
PATIENTS216
Year 2 Year 3
* * * ** * * ** ** *
130 SLIT
66 CONT
CONTROLS
NS
***
***
baseline 3rd year
PERSISTENTASTHMA
10
20
30
40
50
60
70
% P
AT
IEN
TS
SLIT
***
***
baseline 3rd year
MONOSENSITIZEDPATIENTS
10
20
30
40
50
60
70
% P
AT
IEN
TS