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This study delves into the efficacy of allergen-specific immunotherapy (IT) and explores new developments in the field. Meta-analyses, clinical studies, and immunological mechanisms of subcutaneous IT (SCIT) and sublingual IT (SLIT) are discussed, along with comparison between the two approaches and considerations for polysensitized patients. The research also examines the prevention of asthma development in children with allergic rhinitis (AR) through IT and highlights the importance of patient-doctor cooperation in tailoring treatment to individual needs.
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ALLERGEN SPECIFIC IMMUNOTHERAPY: EFFICACY & NEW DEVELOPMENTS Prof. Dr. Nerin N BahçecilerÖnder Near East UniversityHospital Division of PediatricAllergy & Immunology, Nicosia, Cyprus Montenegro, 2017
Flow • Efficacy – META-ANALYSES /PP / GUIDELINES • Immunologicalmechanism • Long-termefficacy • SCIT or SLIT? Clinicalstudies • Tablet /drop / injection ?? • IT in polysensitizedpatient • New developments • Conclusions
META-ANALYSES: • Asthma / AR • Seasonal / Perreniel • CLINICALLY EFFICIENT
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
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.
Symptom-Medication Scores long-termefficaywith > 4 yrstreament
% of patients with ≤1 new sensitization preventsnewsensitizations in long-term
Persistence of immunological tolerance • Long-termefficacy of SLIT Tablets • Clinicalparameters • Immunologicaltolerance
SCIT or SLIT? Head-to-head comparison Few studies comparing • Efficacy? Adult / children • Safety • Long-term efficacy? • Immunological mechanisms?
Keles S,Bahceciler NN.J Allergy Clin Immunol 2011;128(4):808.
Steroid sparing & asthma attacks Keles S,Bahceciler NN.J Allergy Clin Immunol 2011;128(4):808.
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.
Comparison of Il-10 & specific IgG4 responses • Bothincrease IL-10 • Increase in IgG4 lessandlater in SLIT
ASTMA / AR SMS SCIT comparable SLIT
SCIT specific IgG4 response SCIT SLIT SCIT SLIT IgG4 response in long-term SCIT
SCIT compared to SLIT • ClinicalefficacyEarler in SCIT Comparableafter 1 yr • T cellresponseIL-10, TGF-B comarable • AntibodyresponsesMore IgG4 response in SCIT IgA in SLIT?
SLIT OR SCIT? PATIENT-DOCTOR COOPERATION PATIENT-BASED DON’T GENERELİZE
POLISENSITIZATIONSensitizationstatus in allergypatients %25-75 of PATIENTS POLISENSITIZED
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
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
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
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
AFTER CMD IT PRESCRIPTION CHANGED IN %56.8 OF PATIENTS PRİK CMD
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
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*
ALLERGEN SELECTION IN POLY-ALLERGIC PATIENT Demoly P et al. AllergyAsthma Clin Immunol 2016
Novel Approaches:Expectations Improved Efficacy and Safety?? UNMET NEED CONFIRMATION BY PHASE 3 STUDIES
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