recommendations for appropriate slit trials giovanni passalacqua
DESCRIPTION
RECOMMENDATIONS FOR APPROPRIATE SLIT TRIALS Giovanni Passalacqua. Allergy & Respiratory Diseases Dept.Internal Medicine- IRCCS S.Martino – IST - University of Genoa ITALY CHICAGO-WAO-2013. ISHIZAKA. IgE. NOON. UK CSM. 1986. 2012. Randomized trials. EMPIRICAL USE. 1928. - PowerPoint PPT PresentationTRANSCRIPT
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RECOMMENDATIONSFOR APPROPRIATE
SLIT TRIALS
Giovanni Passalacqua
Allergy & Respiratory DiseasesAllergy & Respiratory DiseasesDept.Internal Medicine-Dept.Internal Medicine-IRCCS S.Martino – IST -IRCCS S.Martino – IST -
University of Genoa ITALYUniversity of Genoa ITALY
CHICAGO-WAO-2013CHICAGO-WAO-2013
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NOON
1928 1960
EMPIRICAL USE
1986 2012
Randomized trials
ISHIZAKA
IgE
1986 2012
SLITPeptides Recombinants Liposomes
Adjuvants
DNA-ITSAllergoids
Th1/Th2
1990
Mechanisms
DURHAM
ROMAGNANI
1998
WHOPos Pap
ILITEPIT
UK CSM
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Where does IT preferentially works?
INFLAMMATIONIgE REACTION
HymenopteraAllergy
FoodAllergy
Seasonalrhinitis
Perennialrhinitis
AsthmaAtopicdermatitis
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Factors to be evaluate in SIT prescription
1 IgE mediated disease2 Clear identification of the responsible allergen3 Severity and duration of symptoms4 Efficacy of pharmacological treatment5 Compliance6 Availability of standardized products7 demonstration of the efficacy
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Standards for practical allergen-specific immunotherapy.
Allergy 2006
Allergen immunotherapy: A practice parameter second updateJACI 2011
WHO Pos Pap. Therapeutical vaccines for allergic diseasesAllergy 1998
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Randomized
Trials
Case Report, Ideas
Editorials, Expert Opinion
Cohort Studies
Case series
Meta-analysis andSystematic reviews
EBM Hierarchy
D
ADBPC trials
E.B.M.E.B.M.Evidence Based MedicineEvidence Based Medicine
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CERTAINTIES - EVIDENCE
GREY AREAS
UNMET NEEDS
UNKNOWN
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Tabella meta analisi
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JACI 2013
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JAMA, 2013
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WAO POS PAP 2013
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JACI 2011
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SymptomScoreRhintis
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JACI 2010
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CERTAINTIES - EVIDENCE
DOUBTFUL
UNMET NEEDS
UNKNOWN
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GRADE: Grading ofRecommendation Assessment, Developing and Evaluation
Quesito clinico(es. efficacia trattamento)
ESAME LETTERATURA
Valutazione della qualitàdella prova sperimentale
SicurezzaPreferenzaCosto
RACCOMANDAZIONEFORTE
RACCOMANDAZIONEDEBOLE
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Should subcutaneous specific immunotherapy be used for treatment of AR in adults without concomitant ASTHMA?
RecommendationWe suggest subcutaneous allergen specific immunotherapy in adults with seasonal AR (conditional recommendation | moderate-quality evidence) and persistent AR caused by mites (conditional recommendation | low-quality evidence).
Should subcutaneous specific immunotherapy be used for treatment of in children without concomitant ASTHMA?
RecommendationIn children with , we suggest subcutaneous specific immunotherapy (conditional recommendation | low-quality evidence).
Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision
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Should sublingual allergen-specific immunotherapy be used in patients with AR and concomitant asthma ?
RecommendationIn patients with AR and asthma, we suggest sublingual specific immunotherapy for treatment of asthma (conditional recommendation | low-quality evidence).
Should subcutaneous allergen-specific immunotherapy be used in patients with AR and concomitant asthma?
RecommendationIn patients with AR and asthma , we suggest subcutaneous specific immunotherapy for treatment of asthma (conditional recommendation | moderate-quality evidence).
Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision
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JACI 2013
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Curr Opin Allergy Clin Immunol 2012
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Pham Ti, PAI 2007
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March 2009
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PROBLEMS:
The majority of the trials were not designed and sized for asthma as primary outcome
Heterogeneity of study designs, duration, dose and evaluation parameters.
Few studies had functional parameters evaluated
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Implications for clinical trials:
If asthma is investigated, the trial should consider asthma as primary outcome
Functional parameters (FEV1, VEMS, oscillometry) should be evaluated
Patients should be symptomatic, or therapeutic control should be evaluated.
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EIFAN
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Implications for clinical trials:
The optimal study design to compare SLIT and SCIT is the DB DD RPC fashion
This is not currently feasible, due to economic limitations.
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AUTHORAnticoDunskyEifanBlazowskiRodriguezDe GrootDe GrootBuyukozurkBuyukozurkRodriguezRodriguez
SEXMFFFMMFMMMF
AGE363111161113272835277
ALLERGLatexMixMixMiteMite
GrassGrassLatexLatexMiteMite
EPINEPH?NNYNYYYYYY
ANAPHYLAXES DUE TO SLIT
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JACI 2013
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Implications for clinical trials:
Adverse events should be described, graded and classified in a standardized fashion
Adverse events should be notified promptly, to monitoring authorities or manufacuturers
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CERTAINTIES - EVIDENCE
DOUBTFUL
UNMET NEEDS
UNKNOWN
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UNSOLVED QUESTIONS
Optimal maintenance regimen (continuous VS pre-coseasonal)
Dose and extract standardization?
Better drugs or SIT?
Polysensitized?
Optimal maintenance SLIT dose for other allergens
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METHODOLOGICAL ISSUES
- HETEROGENEITY OF TRIALS
- DOSES
-PATIENTS’ SELECTION
- PRIMARY OUTCOME/ANALYSIS
- SAMPLE SIZE CALCULATION
- ADHERENCE
- REPORTING
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Patients with symptomsout of the season
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VS PLACEBOSymptoms-28% (-39%)Medications- 24% (-48%)
Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis
Wahn 2009
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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 !!!
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Sastre,Clin Exp Allergy 2010
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GRASSPhl p 1Phl p 5Phl p 6
Phl p 7 (profilin)Phl p 12 (CBP)
BIRCHBet v 1
Bet v 2 (profilin)Bet v 3 (CBP)
PARIETARIAPar j 1Par j 2
Par j 3 (profilin)
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Senna GE, Lomabrdi C, Passalacqua G. JACI 2010
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SCIT: 46 trials
CONSORT: 1 trialFlowchart: 16 trialsDropouts: 12 trialsRandomization: 16 trials
SLIT: 48 trials
CONSORT: 3 trialFlowchart: 20 trialsDropouts: 16 trialsRandomization: 12 trials
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CERTAINTIES - EVIDENCE
DOUBTFUL
UNMET NEEDS
UNKNOWN
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BIOMARKERS
FOR RESPONDER (NON RESPONDER) ?
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JACI, Oct 09
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