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ALLERGEN SPECIFIC IMMUNOTHERAPY: EFFICACY & NEW DEVELOPMENTS

ALLERGEN SPECIFIC IMMUNOTHERAPY: EFFICACY & NEW DEVELOPMENTS. Prof. Dr. Nerin N Bahçeciler Önder Near East University Hospital Division of Pediatric Allergy & Immunology , Nicosia , Cyprus. Montenegro, 2017. Flow. Efficacy – META-ANALYSES /PP / GUIDELINES

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ALLERGEN SPECIFIC IMMUNOTHERAPY: EFFICACY & NEW DEVELOPMENTS

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  1. ALLERGEN SPECIFIC IMMUNOTHERAPY: EFFICACY & NEW DEVELOPMENTS Prof. Dr. Nerin N BahçecilerÖnder Near East UniversityHospital Division of PediatricAllergy & Immunology, Nicosia, Cyprus Montenegro, 2017

  2. Flow • Efficacy – META-ANALYSES /PP / GUIDELINES • Immunologicalmechanism • Long-termefficacy • SCIT or SLIT? Clinicalstudies • Tablet /drop / injection ?? • IT in polysensitizedpatient • New developments • Conclusions

  3. META-ANALYSES: • Asthma / AR • Seasonal / Perreniel • CLINICALLY EFFICIENT

  4. SCIT:Long-termEfficacy PAT (PreventiveAllergyTreatment) Aim: Does SCIT prevent development of ASTHMA in children with AR sensitized to pollens? Duration::3 yrs Method: randomized 208 AR children -92 Controls -97 SCIT Moller et al. JACI, 2002

  5. PREVENTED DEVELOPMENT OF ASTHMA

  6. IMPROVEMENT IN ARC SYMPTOMS

  7. Prospective open controlled Drug ANNUALLY SMS Prick test PC20 Nasal Eo HDM+ AR/Asthma Adults f/up 15 years 3 y 4 y SLIT 5 y J Allergy Clin Immunol 2010:126:969.

  8. Symptom-Medication Scores long-termefficaywith > 4 yrstreament

  9. % of patients with ≤1 new sensitization preventsnewsensitizations in long-term

  10. Durham RS et al. J Allergy Clin Immunol 2012:129:717.

  11. SMS during pollen season

  12. Persistence of immunological tolerance • Long-termefficacy of SLIT Tablets • Clinicalparameters • Immunologicaltolerance

  13. SCIT or SLIT? Head-to-head comparison Few studies comparing • Efficacy? Adult / children • Safety • Long-term efficacy? • Immunological mechanisms?

  14. Comparableefficacy

  15. Keles S,Bahceciler NN.J Allergy Clin Immunol 2011;128(4):808.

  16. Steroid sparing & asthma attacks Keles S,Bahceciler NN.J Allergy Clin Immunol 2011;128(4):808.

  17. SCIT vs SLIT:Differences in immunulogic mechanism INCREASE IN SLIT : IL-10, TGF-b SCIT : IL-10, TGF-b, IgG4 Keles S,Bahceciler NN.J Allergy Clin Immunol 2011;128(4):808.

  18. Improvement in SMS with 2 yrs SLIT & SCIT

  19. Improvement in nasal provocation

  20. Comparison of Il-10 & specific IgG4 responses • Bothincrease IL-10 • Increase in IgG4 lessandlater in SLIT

  21. ASTMA / AR SMS SCIT comparable SLIT

  22. SCIT specific IgG4 response SCIT SLIT SCIT SLIT IgG4 response in long-term SCIT

  23. SCIT compared to SLIT • ClinicalefficacyEarler in SCIT Comparableafter 1 yr • T cellresponseIL-10, TGF-B comarable • AntibodyresponsesMore IgG4 response in SCIT IgA in SLIT?

  24. SLIT OR SCIT? PATIENT-DOCTOR COOPERATION PATIENT-BASED DON’T GENERELİZE

  25. POLISENSITIZATIONSensitizationstatus in allergypatients %25-75 of PATIENTS POLISENSITIZED

  26. allergenic molecule epitope protein Modificato da Aalberse et al. Allergy, 2001 NOMENCLATURE - DIAGNOSTIC TECHNIQUE ALLERGEN SOURCE “allerjen” ALLERGEN SPT MOLECULE SP-IgE B-CELL EPITOPE COMPONENT MOLECULAR Dg (CMD) POLYALLERGIC / POLYSENSITIZED / CO-SENSITIZATION

  27. POLYALLERGIC / POLYSENSITIZED / CO-SENSITIZATION SHARED MOLECULAR STRUCTURE PSODO POLYSENSITIZED SHARED STRUCTURE DIFFERENT STRUCTURE DIFFERENT MOLECULAR STRUCTURE REAL POLYSENSITIZED Bianchi A, et Al. Rivista di Immunologia e Allergologia Pediatrica 01/2011 • 12-19

  28. Birch CBP profilin Mugwort CBP profilin mugwort birch grass ctr negative histamine Prik test SHARED MOLECULAR ST. PSODO POLYSENSITIZED PATIENT 1 Grass Phl p 2 Phl p 1 Phl p 4 Phl p 5 Phl p 6 polcalcin profilin CMD PRIK: POLYSENSITIZED CMD: MONOALLERGIC

  29. mugwort birch grass ctr negative histamine SPT DIFFERENT MOLECULAR St. REAL POLYSENSITIZED HASTA 2 Grass Birch Phl p 2 Phl p 1 Bet v 1 Phl p 4 Phl p 5 Phl p 6 Phl p 7 Bet v 4 Phl p 12 Bet v 2 Mugwort Art v 5 Art v 4 CMD SPT: Polisensitized CMD: Poliallergic Art v 1

  30. AFTER CMD IT PRESCRIPTION CHANGED IN %56.8 OF PATIENTS PRİK CMD

  31. APPROACH TO POLY-ALLERGIC PATIENT AR AND / OR MILD-MODERATE ASTHMA Q 1- SENSITIZATION STATUS? [SPT, sIgE, CRD, Hx] 1 ALLERGEN 2≤ ALLERGENS MONOSENSİTİZED POLİSENSİTİZED Q 2- NUMBER OF ALLERGENS CLINICALLY IMPORTANT? Test resultsandclinicalcorrelation] MONOALLERGIC POLYALLERGIC

  32. ALGORYTHM FOR IT IN POLYALLERGIC PATIENT 2 OR MORE= POLYALLERGIC Q 1- NUMBER OF ALLERGENS RESPONSIBLE FOR SYMPTOMS WHICH MODE OF IT? PATIENT-PHYSICIAN COOPERATION ONE 2 OR MORE SIT WITH 1 ALLERGEN MULTI IT Q 2- ARE ALLERGENS HOMOLOGOUS? START WITH MOST CLINICALLY RELEVANT ALLERGEN YES NO 2 SEPERATE AIT or 1 HOMOLOGOUS MIXTURE 2 SEPERATE AIT or MIXTURE IN SPECIAL CASES*

  33. ALLERGEN SELECTION IN POLY-ALLERGIC PATIENT Demoly P et al. AllergyAsthma Clin Immunol 2016

  34. Novel Approaches:Expectations Improved Efficacy and Safety?? UNMET NEED CONFIRMATION BY PHASE 3 STUDIES

  35. CONCLUSIONS • SCIT /SLIT efficient in AR and ASTHMA in ADULT / CHILDREN • SCIT earlierclinicalefficacysideeffectsmore • SLIT laterclinicalefficacynegligiblesideeffects • SLIT SCIT long-termefficacy • SCIT vs SLIT slightdifferences in immunologicalresponses • Tablet /drop /SC effiicient - PATIENT BASED CHOICE • NovelDevelopments: • CRD in differentiation of Pollyallegy/monoallergy • New therapeuticapproachestoimproveefficacyandsafety

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