hepatitis-c-ttopresentacion-mayo-2014

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ESTADO ACTUAL DEL TRATAMIENTO
DE LA HEPATITIS CRÓNICA C
DR C ENRIQUE ARÚS SOLER
MAGNITUD
Importante problema de salud a nivel mundial
185 millones
personas
infectadas
 1% – 10%
3%
de la población
mundial
Depende de la región geográfica y desarrollo del país
MAGNITUD
1. Primera causa de enfermedad hepática
2. Primera causa de descompensación hepática
3. Primera causa de carcinoma hepatocelular
4. Primera causa de transplante hepático
5.VHC cinco veces mas frecuente que el VIH
Dr. E. Arús Soler
EVOLUCIÓN DE LA EFICACIA DEL TRATAMIENTO DE
LA HEPATITIS CRÓNICA C
TRATAMIENTOS POR VÍA ORAL, LIBRES DE IFN
92 -100%
INTERFERON PEGILADO MAS RIBAVIRINA
MAS TELAPREVIR
67 %
INTERFERON PEGILADO MAS RIBAVIRINA
MAS BOCEPREVIR
66 %
56 %
INTERFERON PEGILADO MAS RIBAVIRINA
39 %
INTERFERON PEGILADO
41 %
INTERFERON MAS RIBAVIRINA 48 SEM
INTERFERON ALFA 48 SEM
INTERFERON ALFA 24 SEM
16 %
6%
NUEVAS DROGAS EN EL TRATAMIENTO
AGENTES ANTIVIRALES DE ACCIÓN DIRECTA
AADS
Fármacos que inhiben directamente la replicación viral
en diferentes momentos del ciclo vital del virus
Inhibidores de la entrada
del virus a la célula
Inhibidores de
Proteasa
NS3 / NS4A
Inhibidores de polimerasa NS5
Dr. E. Arús Soler
Dr. E. Arús Soler
TERAPEÚTICA BÁSICA APROBADA
EN EL 2011
INTERFERÓN
PEGILADO
RIBAVIRINA
INHIBIDORES
DE
PROTEASA
BOCEPREVIR
TELAPREVIR
Dr. E. Arús Soler
NUEVAS ESTRATEGIAS DE
TRATAMIENTO
Terapia triple y cuádruple:
☻ IFN Pegylado
☻ Ribavirina
☻ AADs
Terapia toda por vía oral:
☻ No incluye IFN
☻ Incluye varios AADs
☻ con Ribavirina
☻ sin Ribavirina
Dr. E. Arús Soler
Nucleotide Polymerase Inhibitor
Sofosbuvir plus Ribavirin for Hepatitis C
95
pacientes
Genotipos
Genotipo
2y3
1
GENOTIPO 2 y 3
Medicamento
No. Semanas
Medicamento
No. Semanas
Respuesta
Sofosbuvir Rib
12 semanas
 IFN-P
4 semanas
RVS 100 %
Sofosbuvir Rib
12 semanas
 IFN-P
8 semanas
RVS 100 %
Sofosbuvir Rib
12 semanas
 IFN-P
12 semanas
RVS 100 %
Sofosbuvir Rib
12 semanas
RVS 100 %
Sofosbuvir
12 semanas
RVS 60 %
Sofosbuvir 
IFN-P  Rib
8 semanas
RVS 100 %
Gare EJ. et al N Engl J Med 2013: 368: 34-44
Nucleotide Polymerase Inhibitor
Sofosbuvir plus Ribavirin for Hepatitis C
95
pacientes
Genotipos
Genotipo
2y3
1
GENOTIPO 1
Medicamento
Sofosbuvir Rib
Pacientes naive
No. Semanas
12 semanas
Sofosbuvir Rib
Pacientes
No Respuesta previa
Respuesta
RVS 84 %
RVS 10 %
12 semanas
Gare EJ. N Engl J Med 2013: 368: 34-44
Treatment of HCV with ABT-450/r–
Ombitasvir and Dasabuvir with Ribavirin
ABT- 450/r
Inhibidor de proteasa mas Ritonavir
Ombitasvir
Inhibidor NS5A (Fosfoproteina)
Dasabuvir
Inhibidor de polimerasa
ENSAYO MULTICÉNTRICO CONTROLADO ALEATORIZADO
DOBLE CIEGO CON PLACEBO
PACIENTES
GENOTIPO 1 SIN CIRROSIS
N = 631
Jordan J. Feld, et al N Engl J Med 2014
Treatment of HCV with ABT-450/r–
Ombitasvir and Dasabuvir with Ribavirin
RESPUESTA VIROLÓGICA SOSTENIDA
(12 SEMANAS)
96, 2 %
1a
95,3 %
1b
98%
Jordan J. Feld, et al N Engl J Med 2014
ABT-450/r–Ombitasvir and Dasabuvir
with Ribavirin for Hepatitis C with Cirrhosis
ENSAYO CLÍNICO FASE 3 MULTICENTRO ALEATORIZADO ABIERTO
PACIENTES GENOTIPO 1 CON CIRROSIS (CHILD-PUGH A)
N = 380
RESPUESTA VIROLÓGICA SOSTENIDA
(12 SEMANAS)
91,8 %
12 sem. de tto.
95,9 %
24 sem. de tto.
Fred Poordad, et al N Engl J Med 2014
Retreatment of HCV with ABT-450/r–
Ombitasvir and Dasabuvir with
Ribavirin
ENSAYO MULTICÉNTRICO CONTROLADO ALEATORIZADO
DOBLE CIEGO CON PLACEBO
PACIENTES
GENOTIPO 1 (RECAIDA, RESPONDEDORES
PARCIALES Y
RESPONDEDORES NULOS)
N = 394
RESPUESTA VIROLÓGICA SOSTENIDA
(12 SEMANAS)
96,3 %
95,3%
100%
RECAÍDA
RESP.PARCIAL
95,2%
RESP. NULA
Stefan Zeuzem, et al N Engl J Med 2014
Ledipasvir and Sofosbuvir for Untreated
HCV Genotype 1 Infection
LEDIPASVIR
INHIBIDOR NS5A (FOSFOPROTEINA)
SOFOSBUVIR
INHIBIDOR DE POLIMERASA NS5B
ENSAYO CLÍNICO FASE 3 MULTICENTRO ALEATORIZADO ABIERTO
PACIENTES GENOTIPO 1 NO TRATADOS
(HEPATITIS CRÓNICA Y CIRROSIS)
N = 865
Nezam Afdhal, et al N Engl J Med 2014
Ledipasvir and Sofosbuvir for Untreated
HCV Genotype 1 Infection
RESPUESTA VIROLÓGICA SOSTENIDA
(12 SEMANAS)
LEDISPAVIR MAS SOFOSBUVIR 12 SEM.
99%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 12 SEM.
97%
LEDISPAVIR MAS SOFOSBUVIR 24 SEM.
98%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 24 SEM.
99%
Nezam Afdhal, et al N Engl J Med 2014
Ledipasvir and Sofosbuvir for Previously
Treated HCV Genotype 1 Infection
ENSAYO CLÍNICO MULTICENTRO ALEATORIZADO ABIERTO
PACIENTES GENOTIPO 1 PREVIAMENTE TRATADOS
(HEPATITIS CRÓNICA Y CIRROSIS)
N = 440
RESPUESTA VIROLÓGICA SOSTENIDA
(12 SEMANAS)
LEDISPAVIR MAS SOFOSBUVIR 12 SEM.
94%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 12 SEM.
96%
LEDISPAVIR MAS SOFOSBUVIR 24 SEM.
99%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 24 SEM.
99%
Nezam Afdhal, et al N Engl J Med 2014
Ledipasvir and Sofosbuvir for 8 or 12 Weeks
for Chronic HCV without Cirrhosis
ENSAYO CLÍNICO FASE 3 MULTICENTRO ALEATORIZADO ABIERTO
PACIENTES GENOTIPO 1. NO TRATADOS. SIN CIRROSIS
N = 831
RESPUESTA VIROLÓGICA SOSTENIDA
(12 SEMANAS)
LEDISPAVIR MAS SOFOSBUVIR 8 SEM
94%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 8 SEM.
93%
LEDISPAVIR MAS SOFOSBUVIR 12 SEM
95%
Kris V. Kowdley, et al N Engl J Med 2014
Daclatasvir plus Sofosbuvir for Previously
Treated or Untreated Chronic HCV Infection
ENSAYO CLINICO MULTICENTRO, ALEATORIZADO, ABIERTO
PACIENTES CON HEPATITIS CRÓNICA NO TRATADOS Y
PREVIAMENTE TRATADOS
N = 211
DACLATASVIR
INHIBIDOR DE POLIMERASA NS5A
SOFOSBUVIR
INHIBIDOR DE POLIMERASA NS5B
Sulkowski MS, et al
N Engl J Med 2014;370:211-21.
Daclatasvir plus Sofosbuvir for Previously
Treated or Untreated Chronic HCV Infection
RESPUESTA VIROLÓGICA SOSTENIDA
(12 SEMANAS)
GENOTIPO 1
PACIENTES NO TRATADOS
PREVIAMENTE
DCL, SOF Y RIB
DCL Y SOF
94%
GENOTIPO 2
92%
PACIENTES TRATADOS PREVIAMENTE
IFN-P, RIB, BOC o TEL
98%
98%
GENOTIPO 3
89%
Sulkowski MS, et al N Engl J Med 2014;370:211-21
Recommendations for Testing, Managing,
and Treating Hepatitis C
2014
Grading System Used to Rate the Level of the Evidence and Strength of the
Recommendation
Classification Description
Class I Conditions for which there is evidence and/or general agreement that a given
diagnostic evaluation, procedure, or treatment is beneficial, useful, and effective
Class II Conditions for which there is conflicting evidence and/or a divergence of opinion
aboutthe usefulness and efficacy of a diagnostic evaluation, procedure, or treatment
Class IIa Weight of evidence and/or opinion is in favor of usefulness and efficacy
Class IIb Usefulness and efficacy are less well established by evidence and/or opinion
Class III Conditions for which there is evidence and/or general agreement that a
diagnostic evaluation, procedure, or treatment is not useful and effective or if it in some
cases may be harmful
Level of Evidence Description
Level A Data derived from multiple randomized clinical trials or meta-analyses
Level B Data derived from a single randomized trial, or nonrandomized studies
Level C Consensus opinion of experts, case studies, or standard
Recommended regimen for treatment-naive patients with
HCV genotype 1 who are eligible to receive IFN.
Daily sofosbuvir (400 mg) and weight-based RBV
(1000 mg [<75 kg] to 1200 mg [≥75 kg]) plus weekly PEG for 12 weeks
Class I, Level A
Recommended regimen for treatment-naive patients with
HCV genotype 1 who are not eligible to receive IFN
.
Daily sofosbuvir (400 mg) plus simeprevir (150 mg), with or without
weight-based RBV (1000 mg [<75
kg] to 1200 mg [≥75 kg) for 12 weeks
Class I, Level A
Alternative regimens for treatment- naive patients with HCV
genotype 1 who are eligible to receive IFN.
Daily simeprevir (150 mg) for 12 weeks and weight-based RBV (1000 mg [<75
kg] to 1200 mg [≥75 kg]) plus weekly PEG for 24 weeks
Class IIa, Level A
Alternative regimens for treatment-naive patients with
HCV genotype 1 who are not eligible to receive IFN
Daily sofosbuvir (400 mg) and weight-based RBV(1000 mg [<75 kg] to 1200 mg
[≥75 kg]) for 24 weeks
Class IIb, Level B
The following regimens are NOT recommended for
treatment-naive patients with HCV genotype 1.
PEG/RBV with or without telaprevir or boceprevir for 24 to 48 weeks
Class IIb, Level A
Monotherapy with PEG, RBV, or a DAA
Class III, Level A
Recommended regimen for treatment-naive patients with
HCV genotype 2, regardless of eligibility for IFN therapy
Daily sofosbuvir (400 mg) and weight-based RBV (1000 mg
[<75 kg] to 1200 mg [≥75 kg])for 12 weeks
Class I, Level A
Recommended regimen for treatment-naive patients with
HCV genotype 3 regardless of eligibility for IFN therapy
Daily sofosbuvir (400 mg) and weight-based RBV (1000 mg [<75 kg]
to 1200 mg [≥75 kg]) for 24 weeks
Class I, Level B
The following regimens are NOT recommended for
treatment-naive patients with HCV genotype 2 and 3
PEG/RBV for 24 or 48 weekly
Class I, Level B
Monotherapy with PEG, RBV, or a DAA
Class III, Level A
Telaprevir-, boceprevir-, or simeprevir-based regimens
Class III, Level A
RESPUESTA VIROLÓGICA DURANTE EL
TRATAMIENTO
RESPUESTA VIROLÓGICA RNA-VHC NEGATIVO A LA SEMANA 4 DE TTO.
RÁPIDA ( RVR).
RESPUESTA VIROLÓGICA REDUCCIÓN DE > 2 LOG RNA-VHC A LA
TEMPRANA (RVT)
SEMANA 12 DE TTO. (RVT PARCIAL)
RNA-VHC NEGATIVO A LA SEMANA 12 DE TTO.
(RVT COMPLETA)
RESPUESTA AL FINAL
RNA-VHC NEGATIVO A LA SEMANA 24 O 48
DEL TRATAMIENTO (RFT) DE TTO.
RESPUESTA VIROLÓGICA RNA-VHC NEGATIVO 24 SEMANAS DESPUÉS
SOSTENIDA (RVS)
DE TERMINADO EL TTO.
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