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ALLERGEN SPECIFIC IMMUNOTHERAPY: EFFICACY & NEW DEVELOPMENTS

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Presentation on theme: "ALLERGEN SPECIFIC IMMUNOTHERAPY: EFFICACY & NEW DEVELOPMENTS"— Presentation transcript:

1 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

2 Flow Efficacy – META-ANALYSES /PP / GUIDELINES Immunological mechanism
Long-term efficacy SCIT or SLIT? Clinical studies Tablet /drop / injection ?? IT in polysensitized patient New developments Conclusions

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

4

5

6 SCIT: Long-term Efficacy
PAT (Preventive Allergy Treatment) Aim: Does SCIT prevent development of ASTHMA in children with AR sensitized to pollens? Duration:: 3 yrs SIT astım gelişimini engelliyebilir mi? 7-13 yasında çocuklar ,Avusturya,Danımarka,Fınlan,Almanya ve Isvec den 205 çocuk 6-14 yas arası.. 3 yıl IT sonrası kontrol grupta anlamlı derecede fazla astım hastası bulundu. IT öncesi hastaların %20 sinde astım zaten vardı. Astımlı olmayan hastalar arasında SIT alanlarda 3 yıl sonra daha az astım semptomu vardı. Method: randomized 208 AR children -92 Controls -97 SCIT Moller et al. JACI, 2002

7

8 PREVENTED DEVELOPMENT OF ASTHMA

9 IMPROVEMENT IN ARC SYMPTOMS

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

11 Symptom-Medication Scores
long-term efficay with > 4 yrs treament

12 % of patients with ≤1 new sensitization
prevents new sensitizations in long-term

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

14 SMS during pollen season

15 Persistence of immunological tolerance
Long-term efficacy of SLIT Tablets Clinical parameters Immunological tolerance

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

17 Comparable efficacy

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

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

20 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.

21 Improvement in SMS with 2 yrs SLIT & SCIT

22 Improvement in nasal provocation

23 Comparison of Il-10 & specific IgG4 responses
Both increase IL-10 Increase in IgG4 less and later in SLIT

24

25 ASTMA / AR SMS SCIT comparable SLIT

26 SCIT specific IgG4 response
SCIT SLIT SCIT SLIT IgG4 response in long-term SCIT

27 SCIT compared to SLIT Clinical efficacy Earler in SCIT
Comparable after 1 yr T cell response IL-10, TGF-B comarable Antibody responses More IgG4 response in SCIT IgA in SLIT?

28

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

30 POLISENSITIZATION Sensitization status in allergy patients
%25-75 of PATIENTS POLISENSITIZED

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

32 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

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

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

35 IT PRESCRIPTION CHANGED IN %56.8 OF PATIENTS
AFTER CMD IT PRESCRIPTION CHANGED IN %56.8 OF PATIENTS PRİK CMD

36 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 results and clinical correlation] MONOALLERGIC POLYALLERGIC

37 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*

38 ALLERGEN SELECTION IN POLY-ALLERGIC PATIENT
(Homologous) BIRCH or FAGALES OLEACEAE CUPRESSACEAE GRASSES AND CEREAL WEED POLLEN MITES (≠ SOURCES) VENOM DANDERS MOULDS 1 AIT 2 AIT &/or mixtures 2 AIT Then when AIT is with 2 allergens sources indicated? When 2 allergens are necessary we must evaluate if a mix or parallel AIT will be used. Here the 3 key parameters to take into account. Please note that from a practical point of view when mix is used there is no justification to change the dose. It means that for two allergens the mixture should be ½+ ½ Demoly P et al. Allergy Asthma Clin Immunol 2016

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

40 CONCLUSIONS SCIT /SLIT efficient in AR and ASTHMA in ADULT / CHILDREN
SCIT earlier clinical efficacy side effects more SLIT later clinical efficacy negligible side effects SLIT SCIT long-term efficacy SCIT vs SLIT slight differences in immunological responses Tablet /drop /SC effiicient - PATIENT BASED CHOICE Novel Developments: CRD in differentiation of Pollyallegy/monoallergy New therapeutic approaches to improve efficacy and safety

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