La fibrosi polmonare

03/12/2015
La fibrosi polmonare:
stato dell’arte
Dott.ssa Marialuisa BOCCHINO
Ambulatorio dedicato allo studio e cura della
“Fibrosi polmonare idiopatica e delle altre
interstiziopatie polmonari”
Dipartimento di Medicina Clinica e Chirurgia
Sezione di Malattie dell’Apparato Respiratorio
Università degli Studi di Napoli Federico II
AORN dei Colli- Ospedale Monaldi
Am J Respir Crit Care Med. 2000;161:646-664.
New definition of IPF
• IPF is a specific form of progressive fibrosing
interstitial pneumonia
• Unknown cause
• Occurring in older adults
• Limited to the lungs
• Associated with a histological and/or
radiological pattern of usual interstitial
pneumonia (UIP)
Raghu G, et al. Am J Respir Crit Care Med. 2011;183:788-824.
Am J Respir Crit Care Med 2011; 183: 788-824
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Estimated 5 Year Survival Rates
In caso di fibrosi polmonare
idiopatica,
la diagnosi è prognosi
Lung Cancer (NSCLC)
15%
IPF
<20%
CHF
50%
Colorectal Cancer
62%
Breast Cancer
86%
Prostate Cancer
90%
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Sintomi e funzionalità respiratoria
IPF: storia naturale
Esacerbazione
acuta
0
1
2
3
4
5
Anni
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L’importanza della diagnosi corretta e precoce
Escludere altre patologie con prognosi migliore
Facilitare accesso a centri di riferimento per
trattamenti farmacologici approvati (pirfenidone,
nintedanib) o arruolamento in trial clinici
Precoce valutazione trapianto polmonare
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visceral pleura
honeycombing
bronchiectasis
Interlobular septa
secondary lobule
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L’approccio diagnostico
Clinico
• History
• Physical
• Laboratory
• PFTs
Patologo
Radiologo
• Chest X-ray
• HRCT
• Surgical lung biopsy
TEAM MULTIDISCIPLINARE
GOLD standard diagnostico
Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in
patients with little or no radiological evidence of honeycombing:
secondary analysis of a randomised, controlled trial
In the appropriate clinical setting, for patients with possible usual interstitial
pneumonia pattern on high resolution CT, surgical lung biopsy sampling might
not be necessary to reach a diagnosis of idiopathic pulmonary fibrosis if highresolution CT scans are assessed by experts at regional sites familiar with
patterns of usual interstitial pneumonia and management of idiopathic
interstitial pneumonia.
Lancet Respir Med. 2014
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Should serologic testing for connective tissues
diseases be used in the evaluation of suspected IPF?
• CTD can present with a UIP pattern
• ILD has been described as the sole clinical manifestation
of these conditions
• ILD can precede the overt manifestation of a specific CTD
Serologic tests can help exclude other conditions
Connective tissue
diseases
Recommendation: serologic testing for CTD should be
performed in the evaluation of IPF in the majority of
patients, but may be appropriate in a minority (weak
recommendation, very low-quality evidence)
ESR
ANA
CCP (for RA)
CK
Aldolase
Anti-myositis panel with Jo-1 antibody
ENA panel
–
–
–
–
–
Hypersensitivity
pneumonitis
Scl-70
Ro (SSA)
La (SSB)
Smith
RNP
Hypersensitivity panel
(if exposure history)
Am J Respir Crit Care Med 2011; 183: 788-824
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La complessità clinica della fibrosi polmonare idiopatica
Ipertensione
arteriosa
polmonare
Sindrome
combinata
(enfisema para e centrolobulare)
Malattia da reflusso
gastro-esofageo
Fibrosi polmonare
familiare
IPF
Esacerbazione acuta
OSAS
Neoplasia polmonare
L’importanza del monitoraggio clinico
MMG
Pneumologo
Radiologo
Patologo
TEAM DINAMICO MULTIDISCIPLINARE
Reumatologo
Cardiologo
Gastroenterologo
ORL
Oncologo
GOLD standard gestionale
MMG
•
•
•
•
Progressione di malattia
Risposta al trattamento
Gestione eventi avversi
Precoce riconoscimento e gestione di episodi
esacerbazione acuta
• Gestione delle co-morbidità/fenotipi
• Assistenza di fine vita
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“
Quale terapia?
“
Am J Respir Crit Care Med. 2000;161:646-664.
Pirfenidone preclinical studies
and putative mechanism of action
EVIDENCE-BASED TREATMENT
RECOMMENDATIONS
– Orally available, synthetic molecule
– Exhibits anti-fibrotic properties in a variety
of in vitro studies and in vivo models
– Pirfenidone attenuates:
• Fibroblast proliferation
• Fibrosis-associated proteins and cytokines (TGF-β, PDGF)
• Biosynthesis and accumulation of extracellular matrix
• Accumulation of inflammatory cells (and TNF-α synthesis)
Therapies without a recommendation
(newer data published subsequent to
final formal face-to-face discussion):
• imatinib, sildenafil, BIBF 1120
Raghu G. Eur Respir J. 2011;37:743-746.
Schaefer CJ, et al, Eur Respir Rev 2011;20:85-97.
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Meta-analysis of pirfenidone treatment effect
Event driven analysis (either 10% decline in FVC or all cause
mortality) in studies 004, 006 and SP3
(Progression Free Survival)
Based in part on unpublished data
Spagnolo P, et al. Cochrane Database Syst Rev 2010;9:CD003134.
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Approved by the European Commission
on February 28th 2011
Indicated in mild-to-moderate IPF
patients throught the following
functional criteria:
FVC ≥ 50% of predicted
DLCO ≥ 35% of predicted
6MWT distance ≥ 150 m
Approved by the FDA in
October 2014 for treating
all IPF stages
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Pirfenidone: how to administer
–
Pirfenidone should be taken in the morning, midday, and evening with food
–
Dose titration is recommended:
NINTEDANIB
t.i.d.
t.i.d.
t.i.d.
Maintenance dose (2403
mg/day)
Week 2 (1602
mg/day)
Week 1 (801
mg/day)
–
No dose adjustment is necessary in the elderly or patients with renal or liver impairment
•
•
BIBF 1120 is a potent intracellular inhibitor of tyrosine kinases that is in clinical
development for the treatment of idiopathic pulmonary fibrosis and a number of types
of cancer.
Its targets include platelet-derived growth factor receptors (PDGFR) α and β, vascular
endothelial growth factor receptors (VEGFR) 1, 2, and 3, and fibroblast growth factor
receptors (FGFR) 1, 2, and 3).
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The aim of this 12-month, randomized, double-blind, placebo-controlled, phase 2 trial (To Improve Pulmonary
Fibrosis with BIBF 1120 [TOMORROW]) was to evaluate the efficacy and safety of four different doses of BIBF
1120 in patients with idiopathic pulmonary fibrosis.
Eligible patients :
FVC 50% or more of their predicted value
DLCO 30 to 79% of their predicted value
PaO2 at rest of 55 mm Hg or greater.
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