The Future of Allergy and Clinical Immunology Prof. G. Walter Canonica - Congreso Slaai 2015

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



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



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



66% pa@ents accordingly to Drazen NEJM 2011



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



biomarkers SYSTEMIC INFLAMMOME



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



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

The Future of Allergy and Clinical Immunology Prof. G. Walter Canonica - Congreso Slaai 2015

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