XI Curso Nacional de
Atualização em Pneumologia
Tratamento da Fibrose Pulmonar Idiopática
16/04/2010
Prof. Dr. José Antônio Baddini Martinez
Professor Associado – FMRP-USP
Conflito de Interesse
Nenhum conflito de interesse a
declarar, relacionado com o conteúdo da
presente exposição.
Fibrose Pulmonar Idiopática
Sobrevida mediana entre 3 e 4 anos
I
II
III
IV
(King TE et al., AJRCCM, 164: 1171-81, 2001)
(Ries LAG et al. SEER Survival Monograph. NIH Publication: 07-6215, 2007)
Fibrose Pulmonar Idiopática
Tratamento Convencional
• Estudo retrospectivo, aberto
• Dois centros médicos
• Pareamento por função pulmonar inicial
• Sem tratamento X Pred. + Ciclo.
(n=82)
(n=82)
(Collard HR et al. Chest 2004; 125: 2169-74)
Fibrose Pulmonar Idiopática
Tratamentos Investigados
DROGAS
ALVOS
Imunomodulação
Endotelina
HP
DROGAS
Etarnecept
Zileuton
Octreotida
TTmolibdato
GC-1008
FG-3019
Cobre
Interferon 
Talidomida
HP
Imunomodulação
Angiogênese
Minociclina
Gleevec
Angiogênese
PDGF
QAX576
BIBF 120
IL-13
Enzimas
Interferon 
Bosentana
Iloprost
Sildenafil
ALVOS
TNF-
5 LIPO
Somatostatina
TGF-
CTGF
N-acetilcísteina
•  Produção de GSH
• Antioxidante intracelular
p=0.02
p=0.003
NAC: menor toxidade hematológica
Mortalidade em 1 ano:
NAC: 9% X Placebo: 11%
Pirfenidona
• Droga com ação anti-fibrótica.
• Mecanismos de ação desconhecido.
• Ação anti-TNF-, anti-TGF-, anti-oxidante ?
(9 meses)
Pirfenidona
e Prednisona
Placebo e
Prednisona
p
n
73
36
-
CV (L)
-0,03 ± 0,22
-0,13 ± 0,19
0,037
SaO2
0,46 ± 3,99
-1,59 ± 3,40
0,031
Exacerbações
Agudas
0
5 (14%)
0,003
(Azuma A et al. AJRCCM 2005; 171: 1040-7)
Eur Respir J 2010; 35:821-829
Pirfenidone in idiopathic pulmonary fibrosis
H. Taniguchi1, M. Ebina2, Y. Kondoh1, T. Ogura3, A. Azuma4, M. Suga5, Y.
Taguchi6, H. Takahashi7, K. Nakata8, A. Sato9, M. Takeuchi10, G. Raghu11, S.
Kudoh4, T. Nukiwa2 and the Pirfenidone Clinical Study Group in Japan12
A multicentre, double-blind, placebo-controlled, randomised phase III clinical trial was
conducted in Japanese patients with well-defined IPF to determine the efficacy and
safety of pirfenidone, a novel antifibrotic oral agent, over 52 weeks. Of 275 patients
randomised (high-dose, 1,800 mg·day–1; low-dose, 1,200 mg·day–1; or placebo groups
in the ratio 2:1:2), 267 patients were evaluated for the efficacy of pirfenidone. Prior to
unblinding, the primary end-point was revised; the change in vital capacity (VC) was
assessed at week 52. Secondary end-points included the progression-free survival (PFS)
time. Significant differences were observed in VC decline (primary end-point) between
the placebo group (-0.16 L) and the high-dose group (-0.09 L) (p = 0.0416); differences
between the two groups (p = 0.0280) were also observed in the PFS (the secondary
end-point). Although photosensitivity, a well-established side-effect of pirfenidone, was
the major adverse event in this study, it was mild in severity in most of the patients.
Pirespa® - Shionogi Company
Capacity Studies - InterMune Inc.
• Grupo não representativo: não fumantes e abordados
durante internação hospitalar.
• Só 9 com biópsias pulmonares.
• Inclusão de vidro despolido como critério tomográfico.
• Intervenção não cega.
• Taxa de abandono da anticoagulação: 26%
FPI e Anticoagulação
• Assunto em aberto.
• Ensaio clínico do NIH em planejamento.
Exacerbações Agudas
(Collard HR et al. AJRCCM 2007; 176: 636-643)
• Metil-prednisolona: 0,5 a 1,0 gr/dia por 3 dias.
• Anticoagulação ?
• Ciclosporina ??
• Largo espectro antibiótico + pulsoterapia ???
Respirology (2008) 13, 394-399
Effects of pulmonary rehabilitation in patients with idiopathic
pulmonary fibrosis
OSAMU NISHIYAMA, 1 YASUHIRO KONDOH, 1 TOMOKI KIMURA, 1 KEISUKE KATO, 1 KENSUKE KATAOKA, 1
TOMOYA OGAWA, 2 FUMIKO WATANABE, 2 SHINICHI ARIZONO, 2 KOICHI NISHIMURA 3 AND HIROYUKI
TANIGUCHI 1
Results: Assessment of efficacy was carried out on 13 patients who completed the
programme and 15 patients in the control group. There were no significant effects of the
programme on measures of pulmonary function, values of arterial blood gas analysis or
dyspnoea rating. Although there were some differences in the baseline 6MWD and total
health-related quality of life score which were not statistically significant, marked
improvements were observed in the 6MWD (mean difference 46.3 m (95% CI: 8.3–84.4),
P < 0.05) and the total health-related quality of life score (−6.1 (95% CI: −11.7 to −0.5),
P < 0.05).
Transplante Pulmonar
• Condições psicológica e social
adequadas.
• Sem co-morbidades significativas.
• Idade < 65 anos.
• CVF < 50-60%.
• DLCO < 40%.
• SaO2 < 88% no TC-6m.
• Uso de oxigenoterapia contínua.
• Baixa qualidade de vida.