SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua
description
Transcript of SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua
![Page 1: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/1.jpg)
SUBLINGUAL IMMUNOTHERAPY
Giovanni Passalacqua
Allergy & Respiratory DiseasesAllergy & Respiratory DiseasesDept.Internal Medicine-Dept.Internal Medicine-
University of Genoa ITALYUniversity of Genoa ITALY
![Page 2: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/2.jpg)
THE LITERATURE
66 RDBPC TRIALS
8 RANDOMIZED OPEN TRIALS
6 COMPARATIVE (SLIT vs SCIT)
6 TRIALS IN OTHER DISEASES
![Page 3: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/3.jpg)
10
20
grass
HDM
parietaria
cypress
cat ragweed
birch
other
67%
![Page 4: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/4.jpg)
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
![Page 5: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/5.jpg)
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
![Page 6: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/6.jpg)
Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitisDurham SR, JACI 2006
![Page 7: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/7.jpg)
Prolonged preseasonal treatment with Grazax improves the clinical efficacy
Calderon M et al, Allergy 2007
![Page 8: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/8.jpg)
![Page 9: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/9.jpg)
![Page 10: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/10.jpg)
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 !!!
![Page 11: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/11.jpg)
VS PLACEBOSymptoms-28% (-39%)Medications- 24% (-48%)
Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis
Wahn 2009
![Page 12: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/12.jpg)
VS PLACEBOSymptoms-34% to –44%
![Page 13: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/13.jpg)
VS PLACEBOSymptoms -24% Medications - 34%
![Page 14: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/14.jpg)
Sublingual immunotherapy for allergic rhinitis.Allergy, 2005. Wilson D., Torres Lima I, Durham S.
21 trials
![Page 15: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/15.jpg)
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
![Page 16: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/16.jpg)
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
![Page 17: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/17.jpg)
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
![Page 18: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/18.jpg)
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
![Page 19: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/19.jpg)
49 (OUT OF 60) RDBPC TRIALS SUITABLE FOR POOLING:2333 SLIT2256 PLACEBO
![Page 20: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/20.jpg)
SYMPTOM SCORE
![Page 21: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/21.jpg)
MEDICATION SCORE
![Page 22: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/22.jpg)
SymptomScoreRhintis
![Page 23: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/23.jpg)
JACI 2010
![Page 24: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/24.jpg)
![Page 25: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/25.jpg)
No fatal event reported since 1986
SLIT
![Page 26: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/26.jpg)
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
![Page 27: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/27.jpg)
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.
![Page 28: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/28.jpg)
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
![Page 29: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/29.jpg)
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
![Page 30: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/30.jpg)
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
![Page 31: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/31.jpg)
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
![Page 32: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/32.jpg)
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
![Page 33: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/33.jpg)
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
![Page 34: SUBLINGUAL IMMUNOTHERAPY Giovanni Passalacqua](https://reader035.fdocuments.net/reader035/viewer/2022062315/56815205550346895dc048fe/html5/thumbnails/34.jpg)