Quali futuri farmaci biologici nella terapia dell’Asma ... · Quali futuri farmaci biologici...
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Quali futuri farmaci biologici Quali futuri farmaci biologici nella terapia dellnella terapia dell’’ Asma BronchialeAsma Bronchiale
Andrea MatucciAndrea [email protected]@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)