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Prof. Giorgio Walter Canonica Allergy and Respiratory Diseases Clinic
DIMI-‐University of Genoa IRCCS AOU San Mar:no-‐Genova Italy
President President
SLAAI, March 15, 2015
The Future of Allergy and
Clinical Immunology
The Starting Point
“If it were not for the great variability among individuals, medicine might
have well been a science and not an art.”
Sir William Osler (1849–1919)
Bieber T. 2013
Bieber T. 2013
Fuchs NEJM 2014
Fuchs NEJM 2014
Fuchs NEJM 2014
Collins & Varmus NEJM 2015
Yanez et al. WAO J.2014
Yanez et al. WAO J.2014
Gustaffson et al Gen.Med. 2015
Gustaffson et al Gen.Med. 2015
Gustaffson et al Gen.Med. 2015
The Past/Present
one disease = one drug
The Blockbuster Model
ONE SIZE FITS ALL
The past treatment approach
ReacGve Medicine or
Medicine by AKempts
RENNARD et al., ANNALSATS 2015
Arostegui et al., PLOSone 2014
Arostegui et al., PLOSone 2014
Arostegui et al., PLOSone 2014
BIOMARKER
KATZ et al. AnnalsATS 2014
Taylor RD et al., JACI 2011
PubMed 8 Marzo 2015
BIOMARKERS of asthma phenotyping
Leung et al. Ther.Adv.Resp.Med.2014
Leung et al. Ther.Adv.Resp.Med.2014
Chung et al ERJ 2014
Phenotyping……….
Braido, Holgate & Canonica 2012
Braido, Holgate & Canonica 2012
5
DRAZEN J.M. NEJM September 29, 2011
6
DRAZEN J.M. NEJM September 29, 2011
Braido, Holgate, Canonica. Pulm.Pharm.Ther. 2012
Future scenario in Allergy & Asthma treatment
GENERALISTs
Braido, Holgate, Canonica. Pulm.Pharm.Ther. 2012
Future scenario in Allergy & Asthma treatment
66% pa@ents accordingly to Drazen NEJM 2011
Braido, Holgate, Canonica. Pulm.Pharm.Ther. 2012
Future scenario in Allergy & Asthma treatment
SPECIALISTS
The promise of personalized medicine
• More effective medicines • Safer medicines • Cheaper medicines • Better healthcare • Cheaper healthcare • Less (rather than more)
healthcare disparity
11
Hamburg & Collins 2010
12 Hamburg & Collins 2010
G551D is the third most common muta:on, affec@ng ~4% of pa@ents. For pa:ents homozygous for Δ508, Vertex has another drug, VX-‐809, which acts by increasing the transport of CFTR protein to the cell surface. A phase 2 clinical trial of combined VX-‐809 and VX-‐770 treatment in Δ508 pa:ents is in progress.
Vx-‐770 poten:ates CFTR func:on by promo:ng decoupling between the ga:ng cycle and ATP hydrolysis cycle. Jih KY. et al. PNAS. 2013; 110: 4404-‐9
Vx-‐770; Ivaca[or
A CFTR potentiator in patients with cystic fibrosis and the G551D mutation (most prevalent ga:ng muta:on)
Ramsey BW, et al. N Engl J Med. 2011; 3658: 1663-72
Complex disease will be stratified into a series of pathway specific disorders creating opportunities for
both companion diagnostics and targeted prevention and treatments.
But also a new Taxonomy of disease based upon causative
pathways rather than signs and symptoms.
Crea:on of a New Taxonomy first requires an “Informa:on Commons” in which data on large popula:ons of pa:ents become broadly available for research use and a “Knowledge Network” that adds value to these data by highligh:ng their inter-‐connectedness and integra:ng them with evolving knowledge of fundamental
biological processes
Toward Precision Medicine. US Nat Acad Sci 2011
Reclassification of human disease by identifiable causal pathways
AGUSTI A., Thorax 2014
AGUSTI A., Thorax 2014
AGUSTI A., Thorax 2014
biomarkers SYSTEMIC INFLAMMOME
AGUSTI A., Thorax 2014
AGUSTI A., Thorax 2014
SUSTAINABILITY
The Present/Future
ASTHMA HORIZON PLANNING in the next 5 years
tralokinumab (an@ IL 13, MedImmune)
ligelizumab (an@ IgE, Novar@s)
dupilumab (an@ IL 4 rec,Sanofi Regeron)
Pelaia et al.Nature Medicine 2012
Kupckyk et al. Allergy 2014
Kupckyk et al. Allergy 2014
JACI 2013
ISSN 0091-6749
V O L U M E 1 2 9 N O. 4A P R I L 2 0 1 2
www.jacionline.org
THE JOURNAL OF Allergy AND Clinical Immunology
CURRENT PERSPECTIVESICON: Food allergyThe role of dendritic cells in food allergyROSTRUMMultiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: Looking at the published evidenceHealth literacy and asthmaWORKSHOP SUMMARYUnderstanding the complexity of IgE-related phenotypes from childhood to young adulthood: A Mechanisms of the Development of Allergy (MeDALL) Seminar
CLINICAL REVIEWSAn update on the role of human dendritic cells in patients with atopic dermatitis
MECHANISMS OF ALLERGIC DISEASESThe role of dendritic cells in asthma
EDITORIALSWe call for iCAALL: International Collaboration in Asthma, Allergy and ImmunologyThe airway epithelium in childhood asthmaTH9 cells: In front and beyond TH2Nonimmediate drug allergy: Diagnostic benefit of skin testing and practical approach
OFFICIAL JOURNAL OF
Kim et al. COAI, 2014
Parulekar, AEk & Hanania COAI 2014
Corren et al NEJM, August 3, 2011
Corren et al NEJM August 3, 2011
HIGH Perios.n
Total
LOW perios.n
Hanania et al. AJRCCM 2013
Hanania et al. AJRCCM 2013
2014
et al. AJRCCM 2014
COSTY TREATMENT REQUIREMENTS
Predic.ve Biomarkers of Response
Defini.on of Eligibility to Treatment
Pay by Results Reimbursement
SUSTAINABILITY
Holgate, Brit.J.Clin Pharm.2013
Wenzel S., Nature Med.2012
Auffray et al. Genome Med 2009;1:2
PaEent reported
Clinical
FuncEonal
Cellular
Molecular
Future of phenotyping: ‘Systems Medicine’
Prof. Giorgio Walter Canonica Allergy and Respiratory Diseases Clinic
DIMI-‐University of Genoa IRCCS AOU San Mar:no-‐Genova Italy
President President
SLAAI, March 15, 2015
The Future of Allergy and
Clinical Immunology (Part IV - final)
Mirnezami et al.NEJM 2012
PROJECTIONS FOR MEDICINE
PROJECTIONS FOR TECHNOLOGY
PROJECTIONS FOR INTEGRATION
Chung et al ERJ 2014
Phenotyping……….
Rossi et al Proteomics Clin Appl. 2014
ASTHMA
Rossi et al Proteomics Clin Appl. 2014
Rossi et al Proteomics Clin Appl. 2014
ASTHMA 2
Redhu et al AACI 2013
Pascual R.M. & Peters S.P. J.A.C.I. 2005
Airway Remodeling in Severe Asthma: ASM
Pepe C et al. JACI 2005;116:554-9.
Moderate Asthma
Severe Asthma
Severe Asthma FEV1
SMOOTH MUSCLE AREA
Int.J.Immunopathol. & Pharmacol. 2012
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
t=p/4 x arith
me2
c mean of ortho
gona
l intercep
ts PRE
POST
RESULTS
Riccio, Dal Negro et al.,Int.J.Immunopathol. & Pharmacol.2012
3.00
5.50
8.00
10.50
13.00
BEFORE AFTER TREATMENT
t=p/4 x arith
me2
c mean of ortogon
al
intercep
t
12 month Xolair treatment
RESULTS Riccio, Dal Negro et al.,Int.J.Immunopathol. & Pharmacol.2012
RESPONDER
NON RESPONDER
6.25 µ Severe Asthma Cut off
Mauri et al. Immunol.LeCers 2014
Gal 3-‐GALACTIN 3
Responder Non Responder
Galactin 3 in biopsies
of
Xolair treated patients
Responder Non Responder
Gao et al. Resp Res. 2015
IgE/Eosinophilic Neutrophilic
GalecKn 3
ASTHMA InflammaKon
3 years since Xolair suspension
Nopp et al. Allergy 2010;65:56-60
FEV1
RESPONDER
NON RESPONDER
Gal 3
Galactin 3 as Biomarker of
SUPERESPONDER to
Omalizumab
POSSIBLE CLINICAL MEANING
System Biology
Nature Biotechnology September ,8 2014,
Nature Biotechnology September 8, 2014
System Biology
Lu et al NEJM 2014
Lu et al NEJM 2014
FINAL MESSAGE
Bioinforma2cs, E-‐health records, Bio-‐banks and data protec2on Although ‘omics’ datasets have provided remarkable insights, it is by analysing, linking and comparing different large datasets (genomic, clinical outcomes, imaging etc.) that the greatest insights have been gained – so-‐called ‘big data’.
XVIII Congreso Latinoamericano de Alergia, Asma e Inmunología 2015 Presidente: Alfonso Mario Cepeda Sarabia
Comité Organizador Local: Edgardo Jares, Anahí Yañez, Estrella Asayag Presidentes Sociedad Latinoamericana de Alergia, Asma e Inmunología, Slaai:
2013-2015: Alfonso Mario Cepeda Sarabia - 2015-2017: Juan Carlos Sisul Alvariza Buenos Aires, marzo 14-16, 2015
http://www.slaai2015.com/comites-del-congreso/ Información Slaai: www.slaai.org
Programa Congreso Para Todos Conferencias XVIII Congreso Latinoamericano de Alergia, Asma e Inmunología
Sociedad Latinoamericana de Alergia, Asma e Inmunología, SLaai
