il trattamento dell’epatite c nel futuro prossimo - cisai filestefano fagiuoli u.s.c....
TRANSCRIPT
![Page 1: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/1.jpg)
Stefano Fagiuoli
U.S.C. Gastroenterologia Epatologia e Trapiantologia
Ospedale Papa Giovanni XXIII - Bergamo
Il Trattamento dell’Epatite C nelfuturo prossimo
![Page 2: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/2.jpg)
0
20
40
60
80
100
IFN
6 or
12 mo
IFN+RBV
6 mo
IFN+RBV
12 mo
PEG
2a/b+RBV
12 mo
TVR+PEG
+RBV
6-12 mo
LDV/SOF
2-6 mo
62-63
19-2823
20
0
87
20112011 2013 2013
SV
R R
ate
(%
)
1 – pooled data from ION-1, ION-2, and ION-3
Jeffers L, et al. Hepatology 2004; 39: 1702-1708; Conjeevaram H, et al. Gastroenterology 2006; 131: 470-477; Muir A, et al. N Engl J Med 2004; 350: 2265-71; McHutchison J, et al. Gastroenterology 2000; 119: 1317-1323; Poordad F, et al. N Engl J Med 2011; 364: 1195-206; Bacon B, et al. N Engl J Med 2011; 364: 1207-17; Jacobson I, et al. N Engl J Med 2011; 364: 2405-16; Zeuzem S, et al. N Engl J Med 2011; 364: 2417-28; Manns M, et al. Lancet 2014; 384: 414-426; Jacobson I, et al. Lancet 2014; 384: 403-413; Lawitz E, et al. N Engl J Med 2013; 368:1878-87; Afdhal N, et al. N Engl J Med 2014; 370: 1889-98; Afdhal N, et al. N Engl J Med 2014; 370: 1483-1493; Kowdley K, et al. N Engl J Med 2014; 370: 1879-88.
SMV+PEG
+RBV
6-12 mo
63
2014
SOF+PEG
+RBV
3 mo
951
SVR Rates for Approved Therapies in HCV GT 1 TN or TE
Years are not to scale
42-61
BOC+PEG
+RBV
6-12 mo
20041998 1998
![Page 3: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/3.jpg)
At present
The benchmark for acceptable HCV treatment outcome
is set to > 90%
3
SVR for Approved Therapies in HCV
![Page 4: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/4.jpg)
SVR > 90%
< Toxicity
> Tolerability
Must haves
Short duration
One size fits all: pangenotypic
High barrier to resistance Helpful
Requirements for HCV Therapy
No drug–drug interactions
Low pill burden
Nice
bonus
![Page 5: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/5.jpg)
SVR:
Clinical
Outcomes
Prevent Decompensation
Delay Liver-Related Death
Delay/prevent HCC
Prevent (Improve) Extrahepatic disorders
Cirrhosis regression
Slowing progression of PH
HCV Cirrhosis Natural History: can we modify it ?
![Page 6: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/6.jpg)
But……
With some Caveats……
![Page 7: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/7.jpg)
Hepatology. 2012;56:532-543.
Cirrhosis !
Less fibrosis….. but still Cirrhosis !
![Page 8: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/8.jpg)
Cumulative incidence of hepatic decompensation and hepatic mortality according to:absence (stage 1) or presence (stage 2) of varices in 2 cohorts of HCV patients with
compensated cirrhosis
Gomez EV, et al. J Hepatol 2013Bruno S, et al. Am J Gastroenterol 2009
n= 352 patients n= 402 patients
Clinical Decompensation
Liver-related mortality
![Page 9: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/9.jpg)
Gomez EV, et al. J Hepatol 2013Bruno S, et al. Am J Gastroenterol 2009
n= 352 patients n= 402 patients
Clinical Decompensation
Liver-related mortality
Cumulative incidence of hepatic decompensation and hepatic mortality according to:absence (stage 1) or presence (stage 2) of varices in 2 cohorts of HCV patients with
compensated cirrhosis
![Page 10: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/10.jpg)
The Impact of “Cirrhosis Regression” on Clinical Events
?
Liver-related events Liver-related events
![Page 11: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/11.jpg)
The Impact of “Cirrhosis Regression” on Clinical Events
Liver-related events Liver-related events
?
![Page 12: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/12.jpg)
No SVR
SVR
No SVR
SVR
Pa
tie
nts
aliv
e (
%)
Survival after P/R treatment in 440 patients with HCV cirrhosis, CTP A 5-6 (mean follow-up time 7.7 yrs)
No SVR
SVR
No SVR
SVR
Log rank p = 0.003Log rank p = 0.001
Esophageal varicesbefore P/R
No esophageal varicesbefore P/R
Di Marco V, et al. submitted
![Page 13: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/13.jpg)
LDV+SOF+RBV in G1/G4 HCV patients with decompensated cirrhosis
-6
-4
-2
0
2
4
-6
-4
-2
0
2
4
n=5 n=5 n=2 n=3
(+10)
CPT B CPT C
12 wk (n=30)* 24 wk (n=29)* 12 wk (n=23)* 24 wk (n=26)*
*Missing FU-4: n=2 CPT B 12 wk; n=4 CPT B 24 wk; n=2 CPT C 12 wk; n=7 CPT C 24 wk.
Flamm, AASLD, 2014, Oral #239
![Page 14: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/14.jpg)
LDV+SOF+RBV in G1/G4 HCV patients with decompensated cirrhosis
-6
-4
-2
0
2
4
-6
-4
-2
0
2
4
n=5 n=5 n=2 n=3
(+10)
CPT B CPT C
12 wk (n=30)* 24 wk (n=29)* 12 wk (n=23)* 24 wk (n=26)*
*Missing FU-4: n=2 CPT B 12 wk; n=4 CPT B 24 wk; n=2 CPT C 12 wk; n=7 CPT C 24 wk.
Flamm, AASLD, 2014, Oral #239
36% not improved 35% not improved
![Page 15: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/15.jpg)
Death due to Cirrhosis and HCC after P/R treatments
![Page 16: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/16.jpg)
Eradication of HCV: What about CURE ???
Point of NO RETURN ????
![Page 17: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/17.jpg)
The ……“Too late point”…….?
![Page 18: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/18.jpg)
Factors associated with increased risk of cirrhosis and HCC in patients with HCC
![Page 19: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/19.jpg)
Clinical
Outcomes
Extrahepatic Benefit ????
![Page 20: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/20.jpg)
Extrahepatic Benefit of SVR
![Page 21: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/21.jpg)
Antiviral Treatment and Extrahepatic Outcomes in HCV
End Stage Renal Disease
Hsu et al, Gut 2015; 64: 495-503
Ischemic Stroke
p=0,001
p=0,001p=0,027
p= ns
Acute Coronary Syndrome
Autoimmune Diseases
![Page 22: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/22.jpg)
SVR in diabetics
![Page 23: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/23.jpg)
![Page 24: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/24.jpg)
…….The EARLIER, the WIDER we treat HCV
the better the OUTCOME……
![Page 25: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/25.jpg)
Increasing Use of High SVR Therapy (~ 90%) will Eliminate HCV in the US by 2029
No more
patients
available
to treat
200,000Treated
150,000
100,000
50,000
0
160,000
120,000
80,000
40,000
0
Cured
Razavi H, et al. Hepatology. 2013;57:2164-2170.
![Page 26: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/26.jpg)
EPAC survey 31-12-2013 - Chronic Hepatitis C in Italy
Total expected patients
337-375.000
Patients with diagnosis not attending
to authorized centers87-95000 *
Patients with diagnosis attending to authorized centers
220-250000
Patients without diagnosis ???
Patients excluded:• patients with fatal comorbidities (i.e. neoplasms including HCC)• patients with decompensated cirrhosis (Child C) • older patients (> 85 years old)• pediatric patients
HCV-HIV coinfected patients30000
*Including:• Patients managed by general practitioners• Patients referring to SERD• Incarcerated (25000)• Immigrants• Patients with more than one code
![Page 27: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/27.jpg)
Fibrosis stage % Number of Patients
F0 - F1 45 136.350 / 151.650
F2 15 45.450 / 50.550
F3 11,5 34.845 / 38.775
F4 – Cirrhosis 28,5 86.355 / 96.045Child A 65-77% 62.429-73.954
Child B 15-22% 14.406-21.130
Child C 4-8% 3.482-7.684
F3 + F4 40 131.200 / 134.820
EPAC survey 31-12-2013 - Chronic Hepatitis C in Italy
![Page 28: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/28.jpg)
Widespread
Number and proportion of HCV treatments according to drug price* & estimated prevalence of CHC
Italian patients (#)
Price per Treatment €
Number of Patients treatable according to
budget *
% patients treated x year #
Time required to treat all patients
(Years)
50000 20000 6 16.5
40000 25000 7.5 13.2
30000 33000 10 10
25000 40000 12 8.25
20000 50000 15 6.6
15000 66000 19.7 5
10000 100000 30.3 3
5000 200000 60.6 1.6
2000 Egypt/Indian
500000 all 1
* Budget 1x109 € (or less?) # : ~ 337.000 HCV estimated Italian patients
![Page 29: Il Trattamento dell’Epatite C nel futuro prossimo - CISAI fileStefano Fagiuoli U.S.C. Gastroenterologia Epatologia e Trapiantologia Ospedale Papa Giovanni XXIII - Bergamo Il Trattamento](https://reader031.vdocuments.net/reader031/viewer/2022022800/5c6a905609d3f2310b8cca94/html5/thumbnails/29.jpg)
Tema costo-beneficio
• Nuove terapie COSTOSE≈ 30-35.000 €
• Risorse Limitate ????
• Selezione pazienti ?Deferral informato?
Riflessioni………..