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Epicutaneous immunotherapy Boonthorn 4 december 2009
outline ,[object Object],[object Object],[object Object],[object Object]
Meta-analysis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Enrico C.  et al., Ann Allergy Asthma Immunol.  2009;102:22–28
Specific immunotherapy: current meta-analysis   (Sc IT) Enrico C.  et al., Ann Allergy Asthma Immunol.  2009;102:22–28 Source Patients Characteristics Outcomes Abramson et al 2003 1,064 adults and children Meta-analysis of  RCT  of  asthma Double-blind, single-blind, and open studies 75  studies for outcomes (36 with  HDM , 20 pollen, 10 animal dander, 2  Cladosporium  mould allergy, 1 latex, and 6 multiple allergens) significant  improvements  in asthma symptom scores Calderon et al, 2007 1,063 adults Meta-analysis of randomized DBPC studies of rhinitis 15  studies for outcomes (a variety of allergens were administered: ragweed, mixed grass, timothy,  Parietaria , birch, orchard, cedar, Bermuda grass,  Juniperus ashei , and  Cocos Symptom scores  , Medication scores were reduced  in the immunotherapy
Meta-analysis ( SL IT ) Enrico C.  et al., Ann Allergy Asthma Immunol.  2009;102:22–28 Source Patients Characteristics Outcomes Calamita et al 2006 303 adults and   children Meta-analysis of  randomized placebo-controlled,open and blinded studies of  asthma 9  studies (5 with pollen and 4 with mites) no significant reduction  in asthma symptoms Penagos et al 2008 441 children Meta-analysis of randomized DBPC studies of  asthma 9  studies for the outcomes (6 with mites and 3 with pollens) Overall, there was a  significant reduction  in symptoms Olaguibel et al 2005 256 children Meta-analysis of randomized DBPC clinical trials of respiratory asthma or allergic rhinitis 7  studies for the outcomes  Decreased symptom  and  m edication scor e Penagos et al 2006 484 children Meta-analysis of randomized DBPC studies of  AR 10  studies for the outcomes (6 with pollens and 4 with  HDM  ) There were  significant reductions  in symptom scores   Wilson et al 2005 959 adults and children Meta-analysis of randomized DBPC studies of  AR 22  studies for the outcomes (6 with  HDM , 5 grass pollen, 5  Parietaria , 2 olive, and 1 ambrosia, cat, and cupressaceous Overall there were  significant reductions  in symptoms
Efficacy of specific immunotherapy (SIT). Summary of meta-analysis results expressed as effect size on symptoms.  ( SMD, standardized mean difference  ) Enrico C.  et al., Ann Allergy Asthma Immunol.  2009;102:22–28
Immunological mechanism Nat Rev Immunol 2006;6:761-71
Mechanisms of allergic reactions Nat Rev Immunol 2006;6:761-71
Effects of allergen-specific immunotherapy on clinical and experimental  i mmune parameters Nat Rev Immunol 2006;6:761-71
Proposed role of regulatory T cells and cytokines in allergen-specific immunotherapy Nat Rev Immunol 2006;6:761-71
[object Object]
Epicutaneous is as efficient as subcutaneous desensitization in a mouse model of allergy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JACI .2008;121:793
Epicutaneous is as efficient as subcutaneous desensitization in a mouse model of allergy ,[object Object],JACI .2008;121:793 nontreated EC Sc 8wk 16wk 8wk 16wk 8wk 16wk pollen 174% 139% 67% P<0.001  76% P<0.01 90% P<0.05 57% P<0.01 ovalbumin 291% 171% 79% P<0.01 112% P<0.01 154% P<0.05 86% P<0.05
Epicutaneous is as efficient as subcutaneous desensitization in a mouse model of allergy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JACI .2008;121:793
EPIT for HDM allergy using VIASKIN R  technology : a preclinical study ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JACI .2008;123:S177
EPIT for HDM allergy using VIASKIN R  technology : a preclinical study ,[object Object],JACI .2008;123:S177 Sc EP NT P value sIgG2a Der.f/Der p baseline 0.009/0.075 0.097/0.061 <0.01 After IT 2.009/0.726 2.463/0.468 BAL ( Eo,L) baseline 4.1*10 4 1.0*10 5 1.9*10 5 <0.001  After IT 3.3*10 4 6.9*10 4 2.9*10 5
EPIT for HDM allergy using VIASKIN R  technology : a preclinical study ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JACI .2008;123:S177
EPIT:proof of concept with various Ag in sensitized mouse ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
EPIT:proof of concept with various Ag in sensitized mouse ,[object Object],Doi:10.1016/j.clim.2009.03.254 No significant diff. between EP and sc IgG2a pollen OVA HDM peanuts P value EP ( μ g/ml) 0.97 0.39 2.5 18 <0.05 NT ( μ g/ml) 0.42 0.15 0.5 5.5
EPIT:proof of concept with various Ag in sensitized mouse ,[object Object],Doi:10.1016/j.clim.2009.03.254 Penh value not significant diff. in EP , sc and control Conclusion : in sensitized mice ,with 4 tested allergens, EPIT as efficient as SCIT  Penh value pollen OVA HDM peanuts EP  7.2 4.8 7.6 4.6 NT 12.8 9.7 9.6 7.1
Repeated applications of Peanut protein extracts during EPIT induce a change of cytokine response from Th2 to mixed Th2/Th1 in sensitized mice ,[object Object],[object Object],[object Object],[object Object],Doi:10.1016/j.clim.2009.03.251
Repeated applications of Peanut protein extracts during EPIT induce a change of cytokine response from Th2 to mixed Th2/Th1 in sensitized mice ,[object Object],[object Object],[object Object],[object Object],[object Object],Doi:10.1016/j.clim.2009.03.251
Repeated applications of Peanut protein extracts during EPIT induce a change of cytokine response from Th2 to mixed Th2/Th1 in sensitized mice ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Doi:10.1016/j.clim.2009.03.251
[object Object]
Epicutaneous Immunotherapy In Severe Cow Milk Allergy: A Double Blind Pilot Trial ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JACI .vol.123 ,No.2:s183
Epicutaneous Immunotherapy In Severe Cow Milk Allergy: A Double Blind Pilot Trial ,[object Object],[object Object],[object Object],[object Object],JACI .vol.123 ,No.2:s183
Epicutaneous Immunotherapy In Severe Cow Milk Allergy: A Double Blind Pilot Trial ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],JACI .vol.123 ,No.2:s183
Epicutaneous Immunotherapy In Severe Cow Milk Allergy: A Double Blind Pilot Trial ,[object Object],[object Object],[object Object],[object Object],JACI .vol.123 ,No.2:s183 Active Rx placebo P value Mean maximum tolerated dose at baseline 2.1mL (SD 2.6 ) 4.4 mL (SD 5.9) Mean maximum tolerated dose at 3 mo. 21 ( SD 24.3 ) 5.4 ( SD 5.9 ) P=0.37 Median change from baseline 5.6 mL 0.17 mL P=0.02
Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy ,[object Object],[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
[object Object],[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
Test drug ,[object Object],J Allergy Clin Immunol 2009;124:997-1002
Statistical analysis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
Results J Allergy Clin Immunol 2009;124:997-1002
Safety and tolerability 10  pts .  used topical corticosteroids for total duration of 13  +/-  20 days J Allergy Clin Immunol 2009;124:997-1002
Nasal provocation  ,[object Object],J Allergy Clin Immunol 2009;124:997-1002
Subjective symptom scores J Allergy Clin Immunol 2009;124:997-1002
Use of rescue medication ,[object Object],[object Object],[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
Discussion ,[object Object],[object Object],1.  Presse Med 1959;67:2299-301 2.  Acta Allergologica 1965;XXI:261-7.
Discussion  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
Limitation of study ,[object Object],[object Object],[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
Limitation of study ,[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
Discussion  ,[object Object],[object Object],[object Object],[object Object],[object Object],J Allergy Clin Immunol 2009;124:997-1002
Conclusion  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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epicutaneous immunotherapy

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  • 4. Specific immunotherapy: current meta-analysis (Sc IT) Enrico C. et al., Ann Allergy Asthma Immunol. 2009;102:22–28 Source Patients Characteristics Outcomes Abramson et al 2003 1,064 adults and children Meta-analysis of RCT of asthma Double-blind, single-blind, and open studies 75 studies for outcomes (36 with HDM , 20 pollen, 10 animal dander, 2 Cladosporium mould allergy, 1 latex, and 6 multiple allergens) significant improvements in asthma symptom scores Calderon et al, 2007 1,063 adults Meta-analysis of randomized DBPC studies of rhinitis 15 studies for outcomes (a variety of allergens were administered: ragweed, mixed grass, timothy, Parietaria , birch, orchard, cedar, Bermuda grass, Juniperus ashei , and Cocos Symptom scores , Medication scores were reduced in the immunotherapy
  • 5. Meta-analysis ( SL IT ) Enrico C. et al., Ann Allergy Asthma Immunol. 2009;102:22–28 Source Patients Characteristics Outcomes Calamita et al 2006 303 adults and children Meta-analysis of randomized placebo-controlled,open and blinded studies of asthma 9 studies (5 with pollen and 4 with mites) no significant reduction in asthma symptoms Penagos et al 2008 441 children Meta-analysis of randomized DBPC studies of asthma 9 studies for the outcomes (6 with mites and 3 with pollens) Overall, there was a significant reduction in symptoms Olaguibel et al 2005 256 children Meta-analysis of randomized DBPC clinical trials of respiratory asthma or allergic rhinitis 7 studies for the outcomes Decreased symptom and m edication scor e Penagos et al 2006 484 children Meta-analysis of randomized DBPC studies of AR 10 studies for the outcomes (6 with pollens and 4 with HDM ) There were significant reductions in symptom scores Wilson et al 2005 959 adults and children Meta-analysis of randomized DBPC studies of AR 22 studies for the outcomes (6 with HDM , 5 grass pollen, 5 Parietaria , 2 olive, and 1 ambrosia, cat, and cupressaceous Overall there were significant reductions in symptoms
  • 6. Efficacy of specific immunotherapy (SIT). Summary of meta-analysis results expressed as effect size on symptoms. ( SMD, standardized mean difference ) Enrico C. et al., Ann Allergy Asthma Immunol. 2009;102:22–28
  • 7. Immunological mechanism Nat Rev Immunol 2006;6:761-71
  • 8. Mechanisms of allergic reactions Nat Rev Immunol 2006;6:761-71
  • 9. Effects of allergen-specific immunotherapy on clinical and experimental i mmune parameters Nat Rev Immunol 2006;6:761-71
  • 10. Proposed role of regulatory T cells and cytokines in allergen-specific immunotherapy Nat Rev Immunol 2006;6:761-71
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  • 35. Results J Allergy Clin Immunol 2009;124:997-1002
  • 36. Safety and tolerability 10 pts . used topical corticosteroids for total duration of 13 +/- 20 days J Allergy Clin Immunol 2009;124:997-1002
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  • 38. Subjective symptom scores J Allergy Clin Immunol 2009;124:997-1002
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