RECOMMENDATIONS FOR APPROPRIATE SLIT TRIALS Giovanni Passalacqua
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Transcript of RECOMMENDATIONS FOR APPROPRIATE SLIT TRIALS Giovanni Passalacqua
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
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
Where does IT preferentially works?
INFLAMMATIONIgE REACTION
HymenopteraAllergy
FoodAllergy
Seasonalrhinitis
Perennialrhinitis
AsthmaAtopicdermatitis
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
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
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
CERTAINTIES - EVIDENCE
GREY AREAS
UNMET NEEDS
UNKNOWN
Tabella meta analisi
JACI 2013
JAMA, 2013
WAO POS PAP 2013
JACI 2011
SymptomScoreRhintis
JACI 2010
CERTAINTIES - EVIDENCE
DOUBTFUL
UNMET NEEDS
UNKNOWN
GRADE: Grading ofRecommendation Assessment, Developing and Evaluation
Quesito clinico(es. efficacia trattamento)
ESAME LETTERATURA
Valutazione della qualitàdella prova sperimentale
SicurezzaPreferenzaCosto
RACCOMANDAZIONEFORTE
RACCOMANDAZIONEDEBOLE
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
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
JACI 2013
Curr Opin Allergy Clin Immunol 2012
Pham Ti, PAI 2007
March 2009
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
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.
EIFAN
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.
AUTHORAnticoDunskyEifanBlazowskiRodriguezDe GrootDe GrootBuyukozurkBuyukozurkRodriguezRodriguez
SEXMFFFMMFMMMF
AGE363111161113272835277
ALLERGLatexMixMixMiteMite
GrassGrassLatexLatexMiteMite
EPINEPH?NNYNYYYYYY
ANAPHYLAXES DUE TO SLIT
JACI 2013
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
CERTAINTIES - EVIDENCE
DOUBTFUL
UNMET NEEDS
UNKNOWN
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
METHODOLOGICAL ISSUES
- HETEROGENEITY OF TRIALS
- DOSES
-PATIENTS’ SELECTION
- PRIMARY OUTCOME/ANALYSIS
- SAMPLE SIZE CALCULATION
- ADHERENCE
- REPORTING
Patients with symptomsout of the season
VS PLACEBOSymptoms-28% (-39%)Medications- 24% (-48%)
Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis
Wahn 2009
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 !!!
Sastre,Clin Exp Allergy 2010
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)
Senna GE, Lomabrdi C, Passalacqua G. JACI 2010
SCIT: 46 trials
CONSORT: 1 trialFlowchart: 16 trialsDropouts: 12 trialsRandomization: 16 trials
SLIT: 48 trials
CONSORT: 3 trialFlowchart: 20 trialsDropouts: 16 trialsRandomization: 12 trials
CERTAINTIES - EVIDENCE
DOUBTFUL
UNMET NEEDS
UNKNOWN
BIOMARKERS
FOR RESPONDER (NON RESPONDER) ?
JACI, Oct 09