Personalized Medicine in Asthma & Allergy 2/Sabah Room/Day 2... · Medicel Oy - Keilaniemi 12,...
Transcript of Personalized Medicine in Asthma & Allergy 2/Sabah Room/Day 2... · Medicel Oy - Keilaniemi 12,...
Personalized Medicine in Asthma & Allergy
Canonica G.W.Personalized Medicine Clinic
Asthma & Allergy
PresidentPresident
Milano Italy
GWC reports having received research grants as well as lecture or advisory board fees from:
Canonica G.W. Disclosure of Interests
•A.Menarini•Alk-Abello’•Allergy Therapeutics•Anallergo•AstraZeneca•Boehringer Ingelheim•Chiesi Farmaceutici•Circassia•Danone•Faes•Genentech•Guidotti-Malesci•Glaxo Smith Kline•Hal Allergy•Lofarma•Meda
•Merck•Merck Sharp & Dome•Mundipharma•Novartis•Phadia•Recordati-InnuvaPharma•Roche•Sanofi-Aventis•Schering Plough•Stallergenes•UCB Pharma•Uriach Pharma•Teva•Thermo Fisher•Valeas
Ferrando et al . AAIR 2016
Ferrando et al . AAIR 2016
Clinical phenotypes
in relation to sputum eosinophils
Haldar et al AJRCCM 2008; 178: 218-224
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Drazen J.M. NEJM 2011
Asthma phenotypes
»Type 2 »Non-type 2
Wenzel SE. Nat Med 2012;18(5):716–25.AERD = aspirin exacerbated respiratory disease;
EIA = exercise-induced asthma
Clinico-functional Phenotypes
Molecular phenotypes
Endotypes
Clinical physiologic biologic hereditary characteristics
Add pathobiologic processes at molecular level to clinical phenotype
Identifiable molecular pathway contributes to/causing clinical characteristics associated with
molecular phenotypes
Transition from
Phenotype to Endotype
Wenzel S., Nature Med.2012
Auffray et al. Genome Med 2009;1:2
Patient reported
Clinical
Functional
Cellular
Molecular
Future of phenotyping: ‘Systems Medicine’
Phenotyping……….
Chung et al ERJ 2014
Staton et al. Biomarkers in Medicine
2015
DeFerrari et al. Exp.Rev.Resp.Med. 2015
CLINICAL CHARACTERISTICS
• sympthoms
• QoL
• comorbidity
LUNG FUNCTION
• bronchialhyperreactivity
• airflowobstruction
• RV, FRC
• small airwaysobstruction
INFLAMMATORY BIOMARKERS
• bloodeosinophilia
• sputumeosinophilia
• sputumneutrophilia
• airwaysremodelling
MOLECULAR BIOMARKERS
• Th2-cytokines
• serum IgE
• FeNO levels
• CCL-11
• periostin
• Gal-3
GENOMICS
BIOMARKERS
• unknown
reactivemedicine
personalizedmedicine
hypothesisbased
approach
unbiasedmolecularapproach
biomarkers development
phenotyping evolution
Figure 1: Biomarkers discovery and phenotyping in severe asthma: actuality and perspectives
DeFerrari et al. Exp.Rev.Resp.Med. 2015
Ferrando et al . AAIR 2016
Bunyavanich & Schadt JACI 2015
Bunyavanich & Schadt JACI 2015
From Bench to Bedside
Medicel Oy - Keilaniemi 12, FIN-02150 Espoo, Finland - phone: +358-9-3867092 - [email protected]
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Epigenomics
Genomics
Transcriptomics
Proteomics
Metabolomics
Biologicaldata
Modeling in basic research
Science observes phenomena and objects on multiple layers in a biological system:
ChromosomeChr. scaffoldChromatin fiberNucleosomesGenesRNAPrimary amino acid chainProtein foldingPost-translational modificationsTransport, storageProtein functionDegradation
Medicel Oy - Keilaniemi 12, FIN-02150 Espoo, Finland - phone: +358-9-3867092 - [email protected]
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Epidemiology
Etiology
Diagnosis
Treatment
Response
Clinical observations on population samples and patient cohorts on multiple layers:
Risk factors, markers, e.g.Chemical / molecularAlimentaryFamily history, socialBehavioral, physical activity
Biomarkers of disease, e.g.PhenotypicMolecular
Pharmacokinetics, ADMEPharmacodynamics, MOABiomarkers of response
Biologicaldata
Clinicaldata
Biological attributes of:
Modeling in translational and clinical research
AGUSTI A., Thorax 2014
ASTHMOSOME
Innate Immune Response
Th2 Immune Response
Inflammation
Remodeling
AIT-Allergen ImmunoTherapy
Predisposition
Breastfeeding
Tobacco Smoke
InfectionsEnviroments
LifestylePhenotype
Endotype
Pharma Treatment
Metabolomics
Breathomics
Genomics
Transcriptomics
Proteomics
Interactome
Biomarkers
Biological Treatment
Microbiome
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NEJM 2012
Mirnezami et al.NEJM 2012
Teran et a J.Prot.Res. 2014
Teran et a J.Prot.Res. 2014
Carraro……Baraldi, Allergy 2013
BREATHOMICS
Rossi et al Proteomics Clin Appl. 2014
ASTHMA
Rossi et al Proteomics Clin Appl. 2014
Rossi et al Proteomics Clin Appl. 2014
ASTHMA 2
Ferrando et al . AAIR 2016
Bagnasco et al. Exp Rev Resp Med 2016
Bagnasco et al. Exp Rev Resp Med 2016
THERE IS URGENT NEED
of well trained specialists to lead
the process of
PRECISION MEDICINE
in ASTHMA
in Clinical Practice
1975
1980
1985
1990
1995
LABA/ICS
for mx and
relief(SMART)
Combination
LAßA+ICS
Bronchospasm Inflammation Remodelling
50 years of asthma pharmacotherapy
Montelukast(1998)
Once-daily
LABA/ICS
LAMA
Inhaled
corticosteroid
1972
Long-
acting ß2-
agonists
2000 2005 2010 2015
Omalizumab
(2003)
Short-acting
ß2-agonists
[Chromone]
theophylline
[Nedocromil]
Anti-IL5
MAB
Varricchi et al COAI 2016
Varricchi et al COAI 2016
Bagnasco et al. Int.Arch.All.Imm. 2016
Bagnasco et al. Int.Arch.All.Imm. 2016
Bagnasco et al. Int.Arch.All.Imm. 2016
AIT as PERSONALIZED THERAPY
Identification of MolecularMechanism of disease
Diagnostic Toolfor the Molecular Mechanism
Treatment Blockingthe Molecular Mechanism
Molecular mechanism:IgE, arming effector cells, binds
allergen/component :mediator release & symptoms
Diagnostic Tool:IgE to causal allergen/component detection
Treatment Blockingthe Molecular Mechanism
AIT- Allergen Immunotherapy
(SCIT-SLIT)
Hamburg & Collins, NEJM 2010 [22]Canonica et al. WAO J.2015 [18]
Passalacqua & Canonica, CMA 2015 [23]
Canonica et al. Curr..Opin.Pulm.Med. 2015
(Mosbech et al.,J Allergy Clin Immunol 2014;134:568-75.)
Der p 1
Der p 2 Der f 1
Der f 2
Composition of a new HDM SLIT-tabletGroup 2
Group 1
50/50
MOSBECH ET AL., J.A.C.I 2014
PRIMARY ENDPOINT
ICS Sparing
Virchow et al. JAMA 2016
Virchow et al. JAMA April 26, 2016
1975
1980
1985
1990
1995
LABA/ICS
for mx and
relief(SMART)
Combination
LAßA+ICS
Bronchospasm Inflammation Remodelling
50 years of asthma pharmacotherapy
Montelukast(1998)
Once-daily
LABA/ICS
LAMA
Anti-IL5
MAB
Inhaled
corticosteroid
1972
Long-
acting ß2-
agonists
2000 2005 2010 2015
Omalizumab
(2003)
Short-acting
ß2-agonists
[Chromone]
theophylline[Nedocromil]
AIT
The most important
PLAYER
PATIENT
So…we should
not forget the
starting point
Canonica et al WAO J. 2015
Precision / Personalized Medicine
In this context my perception is :
PRECISION MEDICINEis focused on the ENDOTYPE (or on the
Mechanisms of patient’s disease)
PERSONALIZED MEDICINE
is focused on the PATIENT/PERSON not just on
the mechanism
P4 Medicine
• Predictive
• Preventive
• Personalized
• Partecipatory
Case Report, Ideas
Editorials, Expert Opinion
Cohort Studies
Case series
Meta-analysis and
Systematic reviews
Randomized
DBPC
EBM Hierarchy
D
A
Shekelle BMJ 1999; 318; 593-596
EBM
From EBM to Clnical Recommendation
Evidence-based medicine
Clinical recommendationson efficacy for an intervention
E.B.M
A general process in guidelines evolution
Factors that influence the strengths of a recommendation
• Balance betweendesirable and undesirable effects
• Quality of evidence
• Patients’values and preferences
• Costs
Two Examples
DRUG A:Effective
Safe
Cheap
DRUG B:Effective
Safe
Fast Dissolving Tablet with a good taste
Administration : 18 shots a day
Cost: 300.000 € /year
Third Example
DRUG C:Effective
Cheap
Fast Dissolving Tablet with a good tasteMake the patient sleeping all day long
DIFFICULT to POSITIONING THOSE PRODUCT in CLINICAL RECCOMENDATIONS
although there is Scientific Evidence of Efficacy
From EBM to recommendation
Evidence-based medicine
Clinical recommendationson efficacy for an intervention
recommendationsfor an intervention
Safety
including
post-marketing
surveillance
Health
economics
Patient’s views& Preference
PERSONALIZED TREATMENTASTHMA
Personalized Medicine is
notjust related
to the new biologics
PERSONALIZED TREATMENTASTHMA
A Step by Step approach….......
PERSONALIZED TREATMENTASTHMA
Nowadays this concept is including
also the right choice of
the DEVICE…........Patient’s Preference and Value
Low intrinsic airflow resistance
Cost, reimbursementInsurance coverage
Liked by patients
Ease of UseDeliver wide range of therapies
Clinical Efficacy
Type of prescribed medication: ICS vs. bronchodilators
Patient’s disease severity
Accurate and consistent drug delivery
Robust
the “ perfect inhaler ”
The “least imperfect” inhalerThe inhaler which the patient
can and will use effectively
The poorer the device technique,
the poorer the outcome
Giraud V, Roche N.Eur Respir J 2002;19:246–51
Good users
Misuser, poor coordinators
n= 3709
Misusers good coordinators
Asthma Instability Score AIS (0-best; 9-worst)
Improved inhalation technique
affects outcome
Outpatient management in children with severe asthma improves inhalation technique from 65% to 95% with correct inhaler technique
Kamps AW, et al. Thorax 2003;58:968–73
-Lower corticosteroid dose
-Improved asthma control
Laube et al.ERJ 2011
Laube et al.ERJ 2011
Laube et al.ERJ 2011
Laube et al.ERJ 2011
Laube et al.ERJ 2011
Laube et al.ERJ 2011
Laube et al.ERJ 2011
CHILDREN & ELDERLY
>250 inhaler devices and medications1
Inhalers
for
COPD & Asthma
SABAs
LABAs
LAMAsICS
Combination medications
COPD, chronic obstructive pulmonary disease; HCPs, healthcare professionals; ICS, inhaled corticosteroid; LABA. long-acting ß-agonist; SABA, short-acting ß-agonist;
1. Bonini M, et al. COPD Research and Practice. 2015;1:9. 2. Haughney J, et a;.Resp Med CME. 2010;3:125–131.
Given the huge array of available devices:-HCPs may not know all the inhaler key features and the way to use them
-Patients often make mistakes when using their inhalers2
• 41 different brands
• 13 different inhalers
HUNDREDSPOTENTIAL SWITCHES !
To Switch or Not To Switch
Assessment of inhalertechnique iscrucial !
The device is
“intrinsic” part
of each inhaled product
KEY MESSAGE
DEVICE FEATURES
in
REAL LIFE
Norderud Laerum et al.Mult.Pulm.Med.2016
SHELF LIFE and STORAGE ( opened )
Norderud Laerum et al.Mult.Pulm.Med.2016
Patient reported device
control frequencies
Norderud Laerum et al.Mult.Pulm.Med.2016
Canonica et al. J.Aerosol Med.Pulm.Drug.Del. 2015
Canonica et al. J.Aerosol Med.Pulm.Drug.Del. 2015
Canonica et al. J.Aerosol Med.Pulm.Drug.Del. 2015
Canonica et al.J.Aerosol Med.Pulm.Drug.Del. 2015
Canonica et al.J.Aerosol Med.Pulm.Drug.Del. 2015
Canonica et al. J.Aerosol Med.Pulm.Drug.Del. 2015
Canonica et al. J.Aerosol Med.Pulm.Drug.Del. 2015
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Canonica et al. J.Aerosol Med.Pulm.Drug.Del. 2015
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Canonica et al. J.Aerosol Med.Pulm.Drug.Del. 2015
KEY MESSAGES
TAKE HOMEMESSAGE
AGUSTI A., Thorax 2014
Gustaffson et al Genome Medicine 2015
Gustaffson et al Genome Medicine 2015
WC
GWC 2016
BLOOD BIOMARKERS URINE BIOMARKERS
BAL BIOMARKERS EXHALED BIOMARKERS INFLAMM BIOMARKERS
OUTDOOR BIOMARKERS INDOOR BIOMARKERS
THANKS• RICCIO AnnaMaria
• DE FERRARI Laura
• CHIAPPORI Alessandra
Consiglio Nazionale delle Ricerche
Istituto di Tecnologie Biomediche
Unità di Proteomica e Metabolomica
• Diego BAGNASCO
• Matteo FERRANDO
• Alice BRAGANTINI
• Stefano BERNARDI
• Marcello MINCARINI
• Filippo TARCHINO
• Anthi ROGKAKOU
• Ilaria BAIARDINI
• Fulvio BRAIDO
• Giovanni PASSALACQUA
MAURI Pierluigi
ROSSI Rossana
DI SILVESTRE Dario
BENAZZI Louise
VARRICCHI Gilda
HEFFLER Enrico
PUGGIONI Francesca
THANK YOU