escenarios futuros sin ifn ¿y sin rbv? - sochinf.cl · negativo positivo hbsag vhc n = 4.904 n =...
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Escenarios futuros sin IFN
¿y sin RBV?
III Curso Hepatitis
Sociedad Chilena de Infectología Agosto 2014
Dr. Carlos Beltrán
Hospital Barros Luco Trudeau
Universidad de Santiago
Grupo SidaChile
¿Cuál es la magnitud del problema
en Chile?
ENS 2003: 0,12% RIBA
Donantes 0,3%
Ref.: 1,15% (RIBA 0,83%)
Soza A, et al. Rev Med Chile 2006; 134: 777 - 788
¿Cuál es la prevalencia en Chile?
Prevalencia VHB – VHC en VIH
91,3%
8,7%
Negativo Positivo
97,7%
2,3%
Negativo Positivo
HBsAg VHC
N = 4.904 N = 3.191
72 casos 426 casos
Evolución serología basal VHC
1,9%1,6%1,7%2,0%1,7%3,6%4,8%2,3%0,0%7,7%
0%
20%
40%
60%
80%
100%
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
VHC (-) VHC (+)VHB: 8,7%
VHC: 2,3%
VHC crónico en USA:
Subdiagnosticado y no tratado
Hepatitis C Monitor. Ipsos Healthcare.
0
500
1000
1500
2000
2500
3000
3500
4000
4500
Nu
mb
er
(in
‘000s)
Prevalence Diagnosed Treated
4.1 M
1.6 M
89,000
38% Diagnosed
5.5% Treated
Unaware of Infection
2.7-3.9 million
infected
50% HCV
detected
32% to 38%
referred for care
7% to 11%
treated
Asrani S, et al. Curr Gastroenterol Rep. 2014;16:381
*Mortality rates = HBV, HCV, HIV listed as cause of death
Because decedent can have multiple causes of death, a record listing more than 1 type of infection was counted for
each type of infection
Tasas de mortalidad en USA,
1999-2007
Ly KN, et al. Ann Intern Med. 2012;156:271-278
7
6
5
4
3
2
1
0
Rate
per
100,0
00 P
Y*
Yr
Hepatitis B
Hepatitis C
HIV
Replicación VHC asociada con mayor
mortalidad general
Lee MH, et al. J Infect Dis. 2012;206:469-477
All Causes
Cu
mu
lati
ve M
ort
ality
(%
)
30.1%
12.8%
12.4%
P < .001 for comparison among 3 groups
P < .001 for HCV RNA detectable vs
undetectable
Anti-HCV seropositives, HCV RNA detectable
Anti-HCV seropositives, HCV RNA undetectable
Anti-HCV seronegatives
Follow-up (Yrs)
0 2 4 6 8 10 12 14 16 18 20
35
30
25
20
15
10
5
0
SVR y complicaciones de VHC
7.7%
15.6%
HC
C In
cid
en
ce (
%)
0
50
40
30
20
10
0 2 4 6 8 10 12 14 16 18 20 22 24
Time (Yrs)
No SVR
SVR
P = .0009
Purevsambuu T, et al. EASL 2014. Abstract O125.
P = .007 P = .1
P = .04 25
20
15
10
5
0
Rate
s o
f d
e N
ovo
IR
(%
)
Overall HCV GT
1/4
HCV GT
2/3
17%
7%
16%
8% 7%
20%
17/
230
21/
124
6/
78
15/
94
11/
152
6/
30
Non-SVR SVR
Aghemo A, et al. Hepatology. 2012;58:1681-1687.
Distribución mundial por genotipo
Aumento de la SVR de VHC G1 S
VR
(%
)
6%
16%
6 Months
34%
55%
>70%
Jacobson IM. Clin Gastroenterol Hepatol. 2009;7:921-930.
Ghany MG, et al. Hepatology. 2009;49:1335-1374.
Ghany MG, et al. Hepatology. 2011;54:1433-1444.
42% 39%
IFN
12 Months 6 Months
IFN + RBV
12 Months 12 Months
PegIFN
12 Months DAA PegIFN + RBV
PegIFN + RBV
1991
1998
2001
2011
Standard Interferon
Ribavirin
Peginterferon
Direct Acting Antivirals
Aumento de eficacia en falla previa,
especialmente “relapsers” y “partial”
Antivirales de acción directa
NS3/4A NS5A NS5B
Function Serine Protease Component of HCV
Replication Complex
RNA-dependent RNA
polymerase
Drugs Covalent
Boceprevir
Telaprevir
Non-covalent
Faldaprevir
Simeprevir
ABT-450
Asunaprevir
MK-5172
Ledipasvir
Daclatasvir
Ombitasvir
MK-8742
PPI-668
Nucleoside analogs
Sofosbuvir
Non-nucleoside
BMS-791325
Dasabuvir
Deleobuvir
C E1 E2 p7 NS2 NS3 NS4A NS4B NS5A NS5B
Core Envelope Glycoproteins Protease Serine
Protease
Helicase Serine
Protease
Cofactor
RNA-dependent
RNA polymerase Component of
HCV Replicase
Preferred Treatment
Recommendations: Initial Therapy
or Relapsed after Prior PR
AASLD-IDSA
Genotype 1 IFN eligible
IFN ineligible†
Sofosbuvir + PR 12 weeks
Sofosbuvir + simeprevir* ± RBV 12 weeks
Genotype 2 Sofosbuvir + RBV 12 weeks
Genotype 3 Sofosbuvir + RBV 24 weeks
Genotype 4 IFN eligible
IFN ineligible
Sofosbuvir + PR 12 weeks
Sofosbuvir + RBV 24 weeks
Genotype 5 or 6 Sofosbuvir + PR 12 weeks
AASLD and IDSA. Available at: http://www.hcvguidelines.org/full-report-view. Version March 21, 2014
PR: Pegylated interferon + Ribavirin.
† Currently recommended only for patients who require immediate treatment.
*For genotype 1a, baseline resistance testing for the Q80K polymorphism should be performed and alternative treatments considered if this mutation is present.
Do not treat decompensated cirrhosis with PegIFN or simeprevir
Preferred Treatment
Recommendations: Partial or Null
Response to Prior PR†
AASLD-IDSA
Genotype 1
Prior PR Sofosbuvir + simeprevir ± RBV 12 weeks
Prior PR-based
triple therapy
Sofosbuvir 12 weeks + PR 12-24 weeks
Genotype 2 Sofosbuvir + RBV 12 weeks
Genotype 3 Sofosbuvir + RBV 24 weeks
Genotype 4 Sofosbuvir + PR 12 weeks
Genotype 5 or 6 Sofosbuvir + PR 12 weeks
AASLD and IDSA. Available at: http://www.hcvguidelines.org/full-report-view. Version March 21, 2014
PR: Pegylated interferon + Ribavirin. †Consideration should be given to postponing treatment, pending release of new drugs for patients with limited hepatic fibrosis (F 0-2)
Do not treat decompensated cirrhosis with PegIFN or simeprevir
EASL HCV Guidelines 2014: Genotype 1
Genotype Options for Therapy
Genotype 1*
PegIFN/ribavirin + sofosbuvir: 12 wks (A1)
PegIFN/ribavirin + simeprevir†: 12 wks, followed by 12 wks of pegIFN/
ribavirin in previously untreated pts and prior relapsers (A1), or 36 wks of
pegIFN/ribavirin in previous partial responders and null responders (B1)
PegIFN/ribavirin + daclatasvir (genotype 1b only; B1): 12 wks followed by 12
wks of pegIFN/ribavirin alone or a further 12 wks of pegIFN/ribavirin +
daclatasvir (response-guided therapy) (B2)
Sofosbuvir + ribavirin: 24 wks for interferon-intolerant pts only, where no
other interferon-free option available (B2)
Sofosbuvir + simeprevir: 12 wks (ribavirin may be added for previous
nonresponders & cirrhotics) (B1)
Sofosbuvir + daclatasvir: 12 wks in previously untreated pts; 24 wks in
treatment-experienced patients (including TVR/BOC-experienced patients)
(ribavirin may be added in previous nonresponders and cirrhotics) (B1)
EASL. J Hepatology. 2014;60:392-420.
*In settings where recommended options are not available, treatment with pegIFN/ribavirin + TVR or BOC remains acceptable. †Not recommended in pts with genotype 1a and detectable Q80K polymorphism.
Argumentos para el tratamiento IFN-
Free de VHC
Inconvenientes de las terapias basadas en IFN
Tolerabilidad
Alto porcentaje de pacientes no elegibles para IFN
Larga duración del tratamiento
Bajas tasas de SVR comparado con los antivirales
PR: ~40-50% en pacientes naïve
Terapia triple PR + Boceprevir o Telaprevir: ~70%
Muchos factores del paciente y el virus que afectan la
elegibilidad o la tasa de respuesta (Raza, IL28B,
cirrosis, tratamiento previo, etc)
Desarrollo de resistencia
Uso inyectable
GT1 HCV Tx Naive: SVR Rates With
12 Wks of IFN-Free Tx in Phase II Studies
Few or no cirrhotic patients included in above studies
Usually monoinfected patients
1. Lalezari LP, et al. EASL 2013. Abstract 845. 2. Gane E, et al. EASL 2013. Abstract 14.
3. Lawitz E, et al. AASLD 2013. Abstract 215. 4. Sulkowski MS, et al. AASLD 2012. Abstract LB-2.
5. Kowdley K, et al. EASL 2013. Abstract 3. 6. Everson G, et al. AASLD 2013. Abstract LB-1.
7. Lawitz E, et al. AASLD 2013. Abstract 76. 8. Sulkowski M, et al. EASL 2013. Abstract 1423.
Regimen N Study SVR 4/12, %
SOF (NS5B) + RBV 25 QUANTUM[1] 56
SOF (NS5B) + RBV 25 ELECTRON[2] 84
SOF (NS5B) + LDV (NS5A) 19 LONESTAR[3] 95
SOF (NS5B) + DCV (NS5A) ± RBV 82 AI-444040[4] 98-100
ABT-450 (PI) + ABT-267 (NS5A) + ABT-333 (NS5B) ± RBV 158 AVIATOR[5] 94
DCV (NS5A) + ASV (PI) + BMS-791325 (NS5B) 161 A1443-014[6] 92
MK-5172 (PI) + MK-8742 (NS5A) ± RBV 65 C-WORTHY[7] 96-100
ION 1: SOF/LDV FDC
RBV for 12 or 24
Wks in Treatment-Naive GT1 Patients
Open-label phase III trial[1,2]
15% to 17% of participants had cirrhosis
Mangia A, et al. EASL 2014. Abstract O164
Afdhal N, et al. N Engl J Med. 2014;370:1889-1898
Sofosbuvir/ledipasvir 400/90 mg FDC tablet once daily; weight-based RBV 1000-1200 mg/day.
SOF/LDV + RBV (n = 217)
SOF/LDV (n = 214)
Wk 24
Treatment-naive pts with HCV GT1
(N = 865)
SOF/LDV + RBV (n = 217)
SOF/LDV (n = 217)
Wk 12
ION 2: over 100 previous null responders
The same 4 arms
ION 1: SVR12 With 12 or 24 Wks SOF/LDV
RBV in Tx-Naive Pts by Cirrhosis Status
SVR12 rates did not differ by
GT1a vs GT1b in any treatment
arm
Virologic failure: 1 breakthrough;
2 relapses
Higher incidence of AE and lab.
abnormalities in the RBV-
containing arms
Fatigue, insomnia, asthenia,
irritability, rash, cough,
pruritus, and anemia
AE rates were generally higher in
the 24-week arm
Mangia A, et al. EASL 2014. Abstract O164
Afdhal N, et al. N Engl J Med. 2014;370:1889-1898
No cirrhosis Cirrhosis
179/180
32/34
178/184
33/33
181/184
31/33
179/181
36/36
12 Wks 24 Wks
SOF/LDV + RBV SOF/LDV + RBV SOF/LDV SOF/LDV
SV
R1
2 (
%)
100
80
60
40
20
0
99 94 97 100 100 99 94 98
ION-2: SOF/LDV FDC
RBV for 12 or 24
Wks in Treatment-Experienced, Cirrhotic
Patients 95,4
100 98,9 98,9
86,481,8
100 100
0
20
40
60
80
100
LDV/SOF
SV
R12, %
Pati
en
ts
LDV/SOF + RBV
LDV/SOF LDV/SOF + RBV
12 Wks 24 Wks
n=87 n=22 n=89 n=22 n=87 n=22 n=89 n=22
Afdahl N, et al. NEJM 2014. DOI 10/1056
Afdhal N, et al. NEJM 2014 DOI: 10.1056
Cir
rhosis
Cir
rhosis
Cir
rhosis
ION 2: Efficacy rate 99% in 24 Wks
Between 96 AND 100% with 12 Wks
In cirrhotic – null responders 24 Wks better
ION-3: Sofosbuvir/Ledipasvir + RBV in
Treatment-Naïve, HCV Genotype 1
Kowdley KV, et al. N Engl J Med. 2014;April 10. [Epub ahead of print].
Sofosbuvir/Ledipasvir QD (n=215)
Sofosbuvir/Ledipasvir QD (n=216)
Phase 3
Open-label, non-inferiority
Genotype 1, Treatment-naïve
Non-cirrhotic
8 vs 12 weeks
Wk 0 8 12 24
ELECTRON Study arm
Sofosbuvir + Ledipasvir + RBV for 6 weeks
Treatment naïve, non – cirrhotics
SVR 68%
Sofosbuvir/Ledipasvir QD + RBV (n=216)
SV
R12 (
%)
94% 95%
No RBV (n=215)
8 wks 8 wks, with RBV 12 wks
RBV (n=216)
8 Weeks
No RBV (n=216)
93%
*Met non-inferiority criteria (12% margin) for all between group comparisons.
12 Weeks
Overall SVR12* Sofosbuvir/Ledipasvir QD
SV
R1
2 (
%)
93% 95%
Genotype 1a (n=171/172/172)
Genotype 1b (n=43/44/44)
92% 98% 98% 96%
SVR12 by HCV Subtype
Kowdley KV, et al. N Engl J Med. 2014;April 10. [Epub ahead of print].
ION-3: Sofosbuvir/Ledipasvir + RBV in
Treatment-Naïve, HCV Genotype 1
COSMOS: Simeprevir + Sofosbuvir
RBV in Genotype 1 HCV Patients
Randomized phase IIa study
Simeprevir 150 mg QD; sofosbuvir 400 mg QD; weight-based RBV 1000-1200 mg/day.
Patients With GT1 HCV
Cohort 1: Previous null responders,
F0-F2[1]
(N = 80)
Cohort 2: Naives and previous null
responders, F3-F4[2] (N = 87)
Simeprevir + Sofosbuvir + RBV (n = 30)
Simeprevir + Sofosbuvir (n = 16)
Wk 12 Wk 24
Simeprevir + Sofosbuvir (n = 14)
Simeprevir + Sofosbuvir + RBV (n = 27)
1. Sulkowski M, et al. EASL 2014. Abstract O7. 2. Lawitz E, et al. EASL 2014. Abstract O165.
0
20
40
60
80
100
SV
R12 (
%)
Simeprevir + Sofosbuvir
PR Null responders F0 – F2
93%
24 Weeks (n=15/24)
12 Weeks (n=14/27)
No RBV With RBV
96% 93%
79%
Sulkowski M, et al. EASL International Liver Congress, 2014. Abstract O7.
Jacobson IM, et al. Hepatology. 2013;58(suppl 1):73A. Abstract LB-3.
COSMOS: Simeprevir + Sofosbuvir ±
RBV in Genotype 1 HCV Patients
SAPPHIRE I & II: ABT- 450/RTV/Ombitasvir +
Dasabuvir + RBV in Noncirrhotic GT1 Pts
Double-blind, placebo-controlled phase III trials in treatment-naive
(SAPPHIRE I) and treatment-experienced (SAPPHIRE II) GT1 HCV pts
Placebo (n = 158)*
ABT-450/RTV/Ombitasvir + Dasabuvir + RBV (n = 473)
Wk 12
1. Feld JJ, et al. EASL 2014. Abstract O60. 2. Feld JJ, et al. N Engl J Med. 2014;370:1594-1603.
3. Zeuzem S, et al. EASL 2014. Abstract O1. 4. Zeuzem S, et al. N Engl J Med. 2014;370:1604-1614.
ABT-450/RTV/ombitasvir 150/100/25 mg once daily; dasabuvir 250 mg twice daily; RBV 1000-1200 mg/day.
*Placebo recipients crossed over to active treatment regimen at Wk 12.
Treatment-naive noncirrhotic pts with HCV GT1[1,2]
(N = 631)
Treatment-experienced noncirrhotic pts with HCV GT1[3,4]
(N = 394) Placebo (n = 97)
ABT-450/RTV/Ombitasvir + Dasabuvir + RBV (n = 297)
SAPPHIRE I & II: SVR12 by HCV Subtype and
Previous Treatment
Zeuzem S, et al. EASL 2014. Abstract O1. Zeuzem S, et al. N Engl J Med. 2014;370:1604-1614.
Previous Response
Relapse Partial response Null response
SV
R12 (
%)
100
80
60
40
20
0 All Patients GT1a GT1b
95.3 100
95.2 94.0 100 100
95.4 97.2 94.9
SAPPHIRE-1:
GT1 Tx-Naive Noncirrhotic Pts:
ABT-450/r 267 FDC
+ ABT-333 + RBV for 12 Wks
n/N = 455/
473
307/
322
148/
151
100
80
60
40
20
0
SV
R12 (
%)
96 95 98
Overall GT1a GT1b
TURQUOISE-II: ABT-450/r/ABT-267 +
ABT-333 + RBV in Compensated Cirrhotics
Poordad F, et al. N Engl J Med 2014; 370: 1973-1982.
3D + RBV (n=208)
Wk 0 12 24
3D + RBV (n=172)
Phase 3
Open-label Genotype 1
Treatment-naïve and
PR experienced
Child-Pugh A
SV
R12 (
%)
92% 96%
12-Week 24-Week
SV
R1
2 (
%)
89% 98% 94% 100%
12-Week 24-Week
1a
1b
PEARL-III: ABT-450/r/Ombitasvir + Dasabuvir
+ RBV in Treatment-Naïve, HCV Genotype 1b
Ferenci P, et al. N Engl J Med 2014; 370: 1983-1992
Phase 3
Double-blind
Genotype 1b; Treatment-naïve
Non-cirrhotic
3D + RBV (n=210)
Wk 0 12 24
3D + Placebo (n=209)
0
20
40
60
80
10099% 99%
3D 3D + RBV
SV
R1
2 (
%)
Non-inferiority criteria (10.5% margin)
met for 3D + RBV versus 3D without RBV
SVR12 rates in both arms were similar
across patient subgroups
Baseline HCV RNA, IL28B, fibrosis
stage, gender, race
HALLMARK-DUAL: Daclatasvir +
Asunaprevir in Patients With GT1b HCV
Better results in Genotype 1b
AI447-028: double-blinded, placebo-controlled phase III trial
Manns M, et al. EASL 2014. Abstract O166
Daclatasvir 60 mg once daily; asunaprevir 100 mg twice daily.
*Patients allocated placebo crossed over into a separate study after 12 wks.
Placebo* (n = 102)
Daclatasvir + Asunaprevir (n = 203)
Daclatasvir + Asunaprevir (n = 235)
Daclatasvir + Asunaprevir (n = 205)
Wk 24
Treatment-naive (N = 305)
Previous null or partial responders (N = 205)
Interferon ineligible/intolerant
(N = 235)
Wk 12
GT1b HCV
HALLMARK-DUAL Study: Daclatasvir +
Asunaprevir in HCV Genotype 1b
SVR12 rates were similar
Non-cirrhotic (85%) and cirrhotic (84%)
Age, gender, race, IL28B genotype
SVR12 rates were lower with baseline
thrombocytopenia (<90 versus >90 x 109
cells/L)
Overall: 71% versus 86%
Advanced fibrosis/cirrhosis: 69% versus 78%
Non-SVR12 achievers (3 treatment arms)
Breakthroughs (4%, 13%, 9%)
Relapse (3%, 4%, 6%)
All had detectable RAVs at time of virologic
failure
Discontinuations due to adverse events: 1.5%
Most common adverse events
Headache, fatigue, diarrhea, nausea, asthenia
Manns M, et al. J Hepatol. 2014;60(suppl 1):S524-S525. Abstract O166.
Kao J-H, et al. J Hepatol. 2014;60(suppl 1):S527-S528. Abstract P1300.
0
20
40
60
80
100
SV
R12 (
%)
90%
82%
Treatment- Naïve
Prior PR Partial/Null Responder
PR Ineligible/ Intolerant
82%
Treatment-naive pts with GT1 HCV and
cirrhosis (N = 123)
MK-5172 + MK-8742 + RBV (n = 31)
MK-5172 + MK-8742 (n = 29)
MK-5172 + MK-8742 + RBV (n = 32)
Wk 12
MK-5172 100 mg once daily; MK-8742 50 mg once daily, RBV 1000-1200 mg divided twice daily.
C-WORTHY: MK-5172 + MK-8742
RBV
in GT1 Cirrhotics and Null Responders
Interim results from a randomized phase IIb trial
Primary endpoint: SVR12
Lawitz E, et al. EASL 2014. Abstract O61
Pts with GT1 HCV and null response
to pegIFN/RBV (N = 130)
MK-5172 + MK-8742 + RBV (n = 31)
MK-5172 + MK-8742 (n = 33)
Wk 18
MK-5172 + MK-8742 (n = 31)
MK-5172 + MK-8742 + RBV (n = 33)
MK-5172 + MK-8742 (n = 32)
C-WORTHY: Interim Results in Ttment -
Naive Cirrhotic Pts and Null Responders
Lawitz E, et al. EASL 2014. Abstract O61
28/ 31
28/ 29
30/ 31*
29/ 30*
*Excludes patients who have not yet reached SVR4 time point.
30/ 32
30/ 33
32/ 32*
29/ 30*
SV
R4
-8 (
%)
100
80
60
40
20
0 Treatment-Naive Pts
With Cirrhosis Null Responders
± Cirrhosis
12 wks + RBV 12 wks no RBV 18 wks + RBV 18 wks no RBV
90
97 97 91 94
100 97 97
HIV-ERADICATE: SOF/LDV en
coinfectados
Osinusi A, et al. EASL International Liver Congress, 2014. Abstract O14.
HIV/HCV Co-infected
HCV Genotype 1
Treatment-Naïve; F0-3
SOF: Sofosbuvir 400 mg daily
LDV: Ledipasvir 90 mg daily
ARV Untreated CD4 count stable and HIV RNA <500 copies OR CD4 count >500 cells/mm3
SVR12
ARV Treated CD4 count >100 cells/mm3 HIV RNA <40 copies Current ARVs ≥8 weeks
Currently SVR4
Regimen N(%)
Tenofovir/Emtricitabine plus
Efavirenz (EFV) 15 (41)
Raltegravir (RAL) 10 (27)
Rilpivirine (RPV) 8 (21)
RPV/RAL 3 ( 8)
EFV/RAL 1 ( 3)
HIV-ERADICATE: SVR
100 100 100 100 100100 100 100
0
20
40
60
80
100
HC
V R
NA
< L
LQ
, %
pa
tie
nts
Wk 8 EOT
13 37
SVR4 SVR12 SVR8
ARV Treated
ARV Untreated
13 30 12 22 10 10
Interim Results
Osinusi A, et al. EASL International Liver Congress, 2014. Abstract O14.
No clinically significant
changes in HIV RNA during
HCV treatment
One patient with transient HIV
viral breakthrough
Missed ARV for 4 days
Re-suppressed on the
same regimen
ARV Untreated (n=13)
ARV Treated (n=37)
C-WORTHY: MK-5172/ MK-8742
RBV
Sulkowski M, et al. EASL International Liver Congress, 2014. Abstract O63.
MK-5172 MK-8742 + RBV
0 12 24
HIV/HCV Co-infected
HCV Genotype 1
Non-cirrhotic
SVR12
SVR12 MK-5172 MK-8742 No RBV
Stable on raltegravir + two NRTIs for 8 weeks prior to enrollment
ART dose modification not permitted during 8 weeks preceding
enrollment unless dose modification due to tolerability failure
CD4 >300 cells/mm3
Undetectable HIV RNA for 24 weeks
C-WORTHY: MK-5172/ MK-8742
RBV
Sulkowski M, et al. EASL International Liver Congress, 2014. Abstract O63.
HC
V R
NA
< L
LQ
, %
pati
en
ts
Week 4 Week 8 Week 12 SVR4
No RBV + RBV Interim Results
100 100 10097
100
90 90 90
0
20
40
60
80
100
29 30 29 30 30 29 29 29
Cost per SVR with TVR or BOC[1,2]
~ $173,000-$189,000
Increased to ~ $257,000-$332,000 in cirrhotics
Estimates
(GT 1 IFN ineligible/intolerant)
SOF/RBV (24 Wks)
SOF/SIM (12 Wks)
Cost per regimen, $ 169,000 150,000
SVR rate, % 52-84 89-100
Base case cost per SVR, $ 244,000 165,000
Costo comparativo de una SVR
Hagan LM, et al. Hepatology. 2014;60:37-45.
El camino del tratamiento del VHC
Terapia triple
PI actuales
P/R
No acceso
• Baja eficacia en G1 (40 – 45%)
• Más baja en VHC/VIH (15-30%)
• Mínima con CV alta, IL28 TT
• Mínima en retratamiento
• Eficacia en G1 (+/-70%)
• Similar VHC/VIH (+/-65%)
• Eficaz con CV alta, IL28 TT
• Similar en relapsers
• Eficacia en G1 (+/-100%)
• Similar VHC/VIH (+/-100%)
• Eficaz con CV alta, IL28 TT
• Similar en relapsers, partial y null
• Simplicidad y tratamiento corto
• Mínimas RAM e interacciones
• Uso en F4 y transplante
DAA (STR)
IFN/RBV free,
short duration,
pangenotypic,
very tolerable,
few DDIs
1-2 DAA + RBV
IFN free,
more tolerable,
fewer DDIs
Resistencia
Costos
El futuro del tratamiento de VHC
Eficacia superior al 90 – 95%
Similar eficacia en cirrosis, fracaso previo, IL28, coinfección VIH
Mínimos efectos colaterales y DDI
Tratamientos coformulados sin IFN y sin RBV
Tratamientos acortados a 8 – 12 semanas ¿excepto en cirrosis - null?
Costos: > US$ 150.000 ¿con acceso en países de menores recursos?
Tratamiento universal si se logra acceso