Quali futuri farmaci biologici Quali futuri farmaci biologici nella terapia dellnella terapia dell’’ Asma BronchialeAsma Bronchiale

Andrea MatucciAndrea Matuccia.matucci@dmi.unifi.ita.matucci@dmi.unifi.it

S.O.D. IMMUNOALLERGOLOGIA

(Dir. Prof. Fabio Almerigogna)

AOU CAREGGI - FIRENZE

XXIX CONGRESSO SEZ. SIAIC TOSCANAVIII CONGRESSO SEZ. SIAIC TOSCANA, EMILIA ROMAGNA E S.

MARINONOVOTEL

11-12 APRILE 2013 - SESTO F.NO (FIRENZE)

Corticosteroids are the mainstay of asthma therapy.

Many of their beneficial effetcs result fromthe modulation of Th2 cytokines

Despite that their activity is nonspecific, there is evidence that corticosteroids aremost effective in individuals in whom Th2 inflammation is crucial

- Wu CY., et al. Eur J Immunol 1991;21:2645—7- Kunicka JE., et al. Cell Immunol 1993;149:39-49- Wenzel S. Nature Med 2012; 18:716-25

Omalizumab

Does defining the phenotype improve the asthma

therapy(ies)?

Tradional nonspecific treatment

(GINA Guidelines)

Futurespecific treatmentwith Biologicals

MEPOLIZUMAB

ILIL--55

et al.

FEV1 ACQ AQLQ

LancetLancet

Mepolizumab: Sindrome di Gleich

ECP (µµµµg/mL)

Data

111 30/6/2008

37 5/5/2011

16 3/6/2011

Riduzione dose giornaliera steroidiRiduzione dose giornaliera steroidi

Vedi Poster n° 104 Vivarelli E., et al.

SNC

Heart

Kidney

Joints

SNP

Churg-Strauss patient Severe Asthma patientAsthma patient

- High dose of steroids (pulse)- Immunosoppressor (CKF)

- Inhalant steroids- High dose of oral steroids- Immunosoppressor (CoA, MTX, AZA)

105 CASES OF CHURG-STRAUSS SYNDROME: TREATMENT STRATEGIES

11 (10,5%)Non Responders

94 (89,5%)Responders

Matucci A, Vultaggio A, et al. (in preparation)

9 2

Mepolizumab:Clinical results

•0-2% Eosinophilia•No asthma symptoms•Steroid sparing

9 2

No availabilityof Mepolizumab

?

TNF-α

GRO-α

IL-8

Rantes

ICAM-1VCAM-1

ChemokinesNeutrophil

Eosinophil

Attractant for:

Adhesion moleculesEndothelial cells

expression

Alternative therapeutic strategies in patients with resistent Churg-Strauss

Anti-TNF-α

TNF-αααα serum levels in Responder and No Responder patients to traditional therapy

75 %

No responders(6/8)

Responders 13,3 %

Large % of patientswith high sTNF-α

Low % of patientswith high sTNF-α

P=0.006

Matucci A, Vultaggio A, Rossi O., et al. (in preparation)

p = 0.01 p = 0.05

0

5

10

15

20

baseline therapy

p = 0.01

Asthma control test

0

5

10

15

20

25

baseline during therapy

CFSV

BECGGM

LM

Asthma control test

scor

e

Infliximab therapy in Churg-Strauss asthmatic patients

Matucci A, Vultaggio A, et al. (in preparation)

et al.

et al.et al.

Antagonism of the PGD2 Receptors in Allergic Diseases

Dep. BIOMEDICINAImmunoallergologia, AOU Careggi

(Prof. Fabio Almerigogna)

University of Florence, ItalyCareggi Hospital

Cammelli DanieleRossi OlivieroVultaggio Alessandra

Nencini FrancescaPratesi SaraPetrone Giulia

Dep. BIOMEDICINEImmunologia e Terapie Cellulari,

AOU Careggi(Prof. Enrico Maggi)