Εξελίξεις στη θεραπεία της CHC

Transcription

1 Εξελίξεις στη θεραπεία της CHC Θεμιστοκλής Γ. Βασιλειάδης Επίκουρος Καθηγητής Παθολογίας Γ Παθολογική Κλινική ΑΠΘ Νοσοκομείο «Γ Παπαγεωργίου»

2 CHC AASLD-IDSA 2015

3 Recommendation for treatment

4 SVR: Sustained Virological Response

5 SVR Associated With Reduced 5-Yr Risk of Death and HCC in All Populations SVR on IFN-based therapy was associated with substantial benefit vs no SVR 62% to 84% reduction in all-cause mortality, 90% reduction in liver transplantation, 68% to 79% reduction in HCC 5-Yr Risk of All-Cause Death by SVR SVR No SVR 5-Yr Risk of HCC by SVR Pts Dead After 5 Yrs (%) General Cirrhotic Pts HIV- Coinfected Pts Pts With HCC After 5 Yrs (%) General Cirrhotic Pts HIV- Coinfected Pts Hill AM, et al. AASLD Abstract 44.

6 Ποιούς θεραπεύουμε

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10 TREATMENT naïve CHC patients

11 The Good News 100 PegIFN DAAs Standard IFN 1991 RBV IFN 6 mos IFN 12 mos IFN/RBV 6 mos IFN/RBV 12 mos PegIFN 12 mos PegIFN/ RBV 12 mos PegIFN/ RBV/ DAA DAA + RBV ± PegIFN

12 HEPATITIS C VIRUS Genome 5 C E1 E2/NS 1 NS2 NS3 NS4A NS4B NS5A NS5B 3 Internal Ribosomal Entry Site RNA Binding Site Envelope Glycoproteins Signal peptide Serine protease/ helicase RNA dependent RNA polymerase STRUCTURAL PROTEINS NONSTRUCTURAL PROTEINS

13 HCV Life Cycle and DAA Targets NS5A inhibitors Block replication complex formation, assembly Receptor binding and endocytosis Transport and release Fusion and uncoating Translation and polyprotein processing (+) RNA LD ER lumen LD Virion assembly NS3/4 protease inhibitors ER lumen Membranous web LD NS5B polymerase RNA replication inhibitors Nucleoside/nucleotide RNA replication Nonnucleoside

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30 How to Use Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir

31 Recommended Regimen Design According to Patient Population Duration and inclusion of ribavirin vary according to patient population GT1 subtype, presence of cirrhosis If subtype is unknown or is mixed, use as described for GT1a HIV coinfection: use regimen and duration as described for HCV monoinfection Population Regimen Duration GT1a, TN or TE, noncirrhotic OMV/PTV/RTV + DSV + RBV 12 wks GT1a, TN or TE, cirrhotic OMV/PTV/RTV + DSV + RBV 24 wks* GT1b, TN or TE, noncirrhotic OMV/PTV/RTV + DSV 12 wks GT1b, TN or TE, cirrhotic OMV/PTV/RTV + DSV + RBV 12 wks GT1, post-olt (Metavir 2) OMV/PTV/RTV + DSV + RBV 24 wks *12-wk course may be considered for some patients based on previous treatment history. Ombitasvir/paritaprevir/ritonavir and dasabuvir [package insert].

32 12 Wks of OMV/PTV/RTV + DSV + RBV in Noncirrhotic GT1a Pts SVR12 (%) n/n = 0 Naive / / 100 SAPPHIRE-I PEARL-IV Experienced / / 87 36/ 36 SAPPHIRE-II 94 47/ 50 All Null responders Partial responders Relapsers Outcome for Subjects Without SVR12, % SAPPHIRE-I PEARL-IV SAPPHIRE-II Virologic failure < Relapse Other Ombitasvir/paritaprevir/ritonavir and dasabuvir [package insert].

33 12 Wks of OMV/PTV/RTV + DSV Without RBV in Noncirrhotic GT1b Pts Naive 100 Experienced All Null responders Partial responders SVR12 (%) Relapsers 20 n/n = 0 209/ 209 PEARL-III 91/ 91 32/ 32 26/ 26 PEARL-II Ombitasvir/paritaprevir/ritonavir and dasabuvir [package insert]. 33/ 33

34 TURQUOISE II: 12 vs 24 Wks of OMV/PTV/RTV + DSV + RBV in Cirrhotics Genotype 1a 12 wks 24 wks Genotype 1b SVR12 (%) n/n = 0 59/ 64 52/ 56 14/ 15 13/ 13 11/ 11 10/ 10 40/ 50 39/ / 140 Naive Relapse Partial Null Overall Treatment Experienced 115/ / 22 18/ 18 25/ 25 20/ 20 6/ 7 3/ 3 14/ 14 10/ 10 67/ 68 51/ 51 Naive Relapse Partial Null Overall Treatment Experienced Poordad F, et al. EASL Abstract O163. Poordad F, et al. N Engl J Med. 2014;370: Ombitasvir/paritaprevir/ritonavir and dasabuvir [package insert].

35 All-Oral Regimens for Other Populations Population Regimen Duration GT2 SOF + RBV [1] 12 wks GT3 SOF + RBV [1] 24 wks GT1/2/3/4 HCC pre-olt SOF + RBV [1] 48 wks* GT1, post-olt (Metavir 2) OMV/PTV/RTV + DSV + RBV [2] 24 wks GT1/4 decompensated cirrhosis (CTP B or C) SOF/LDV + RBV [3] 12 wks GT2/3 decompensated cirrhosis (CTP B or C) SOF + RBV [3] Up to 48 wks *Up to 48 wks or until transplantation, whichever occurs first. Not FDA approved but recommended in AASLD/IDSA guidance. 24 wks of SOF/LDV if anemia or RBV intolerance; 24 wks of SOF/LDV + RBV (600 mg/day with increasing dose if tolerated) if prior SOF failure. Refer to for further information on how to use these therapies 1. Sofosbuvir [package insert]. 2. Ombitasvir/paritaprevir/ritonavir plus dasabuvir [package insert]. 3. AASLD/IDSA HCV Guidelines. Accessed January 5, 2015.

36 Επιστημονική Επιτροπή Ιογενούς Ηπατίτιδας- ΚΕΕΛΠΝΟ

37 Το κόστος των νεότερων φαρμάκων SOVALDI: Euro/Bt OLYSIO : 7500 Euro/Bt DACLATASVIR: 8000 Euro/Bt HARVONI(sofosbuvir+ledipasvir): Euro/Bt

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