Hepatitis C treatment update

Transcription

1 Hepatitis C treatment update Viral Hepatitis Workshop Hepatitis Foundation and Regional Public Health December 2013 Jeffrey S Wong

2 Hepatitis C treatment Non-A non-b hepatitis History of HCV treatment Hutt HCV service Current treatment Future treatment

3 Non-A non-b hepatitis Transmissible hepatitis Blood transfusion Blood products Percutaneous exposure Risk factors for transmission Paid vs. volunteer donor High ALT vs. normal ALT Pooled products Transfusion dose

4 Non-A non-b hepatitis cont. Interferon effective in some with NA-NB Discovery of HCV virus in 1989 Explains 95% of NA-NB Shortly after Screening test Anti-HCV available PCR testing

5 A history of HCV treatment

6 Interferon Protein/Glycoprotein/Cytokine Part of innate immune system Activate several pathways Activate immune cells Upregulate antigen presentation Stimulate more interferon production Responsible for many of the symptoms of viral infection

7 Interferon cont Works for many viruses In HCV however Signalling interference Effector modulation Supression of interferon Genetic variation Chronic infection in 70%

8 Interferon in HCV Used for 25 years Current use in PEG form with Ribavirin Milestones Ribavirin Pegylated Interferon Other important treatment advances Response guided therapy IL28b HCV genotypes

9 Ribavirin Oral nucleoside analogue No SVR rate when used on own Doubles response rate to Interferon Issues/side effects Teratogenic Dose dependent haemolysis

10 Pegylated interferon Interferon attached to Polyethylene glycol Characteristics Given once weekly cf. TIW Improved kinetics Increased side effects Improved response rates cf. standard interferon

11 Response guided therapy Robust stopping rules <2 log drop at week 12 Detectable PCR at 24 weeks Ability to shorten treatment low baseline viral load and negative at 4 weeks Ability to lengthen treatment > 2 log drop at week 12

12 IL 28b Most important host factor predicting response

13 Hepatitis C Genotypes Most important viral factor predicting response 6 genotypes (1-6) G1-45% with 12 months PR G3-70% with 6 months PR G3 associated with more progressive disease

14 History of HCV treatment SVR %

15 Hutt HCV service Nurse led clinic since 2004 Total number treated 176 (Nov 2013) Results (158) Breakthrough 5 (3%) Non responder 19 (12%) Relapser 31 (20%) Sustained viral responder 92 (58%) Treatment discontinued 11 (7%)

16 HCV treatment Positive Young age Maori, Polynesian, and Asian Women Low level of Fibrosis IL28b CC G3 Low Viral Load Negative Older age Caucasian Men Cirrhosis IL28b non CC G1 High Viral Load

17 HCV treatment Now treating older patients with more advanced fibrosis Rimutaka program Monthly nurse led clinic in Rimutaka 5 concurrent patients Insider nurse Well supported by clinic staff

18 Current HCV treatment First generation DAA s Boceprevir and Telaprevir FDA approved in 2011 Boceprevir funded from September 2013 Added to PR improves SVR Genotype 1 only Increased side effects

19 PR +/-Boceprevir SPRINT 1

20 PR + BOC/TVP

21 Future treatments Next generation DAA s Multiple drugs near approval First approvals (FDA) Simeprevir G1 with PR Sofosbuvir G2/3 with R and G1/4 with PR

22 Simeprevir SVR Overall 81% G 1a 81% G 1b 82% IL28b CC 96% IL28b TT 58% F % F 4 65% Manns M et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatmentnaïve patients: results from QUEST-2 a phase III trial. International Liver Congress, Amsterdam, abstract 1413, Jacobson I et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in treatmentnaïve patients: results from QUEST-1 a phase III trial. International Liver Congress, Amsterdam, poster 1425, 2013

23 Sofosbuvir (fission) SVR (SR) SVR SOC Overall 67% 67% G2 97% 78% G3 56% 63% G2 F4 vs. F3 or less 91% vs. 98% G3 F4 vs. F3 or less 34% vs. 61% Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection Eric Lawitz, M.D., Alessandra Mangia, M.D., David Wyles, M.D., Maribel Rodriguez-Torres, M.D., Tarek Hassanein, M.D., Stuart C. Gordon, M.D., Michael Schultz, M.D., Ph.D., Mitchell N. Davis, D.O., Zeid Kayali, M.D., K. Rajender Reddy, M.D., Ira M. Jacobson, M.D., Kris V. Kowdley, M.D., Lisa Nyberg, M.D., G. Mani Subramanian, M.D., Ph.D., Robert H. Hyland, D.Phil., Sarah Arterburn, M.S., Deyuan Jiang, Ph.D., John McNally, Ph.D., Diana Brainard, M.D., William T. Symonds, Pharm.D., John G. McHutchison, M.D., Aasim M. Sheikh, M.D., Zobair Younossi, M.D., M.P.H., and Edward J. Gane, M.D. N Engl J Med 2013; 368: May 16, 2013DOI: /NEJMoa

24 Sofosbuvir (neutrino) Overall 90% G1 89% G4 96% No cirrhosis 92% Cirrhosis 80% IL28b CC 98% IL28b non-cc 87% SVR PR+S Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection Eric Lawitz, M.D., Alessandra Mangia, M.D., David Wyles, M.D., Maribel Rodriguez-Torres, M.D., Tarek Hassanein, M.D., Stuart C. Gordon, M.D., Michael Schultz, M.D., Ph.D., Mitchell N. Davis, D.O., Zeid Kayali, M.D., K. Rajender Reddy, M.D., Ira M. Jacobson, M.D., Kris V. Kowdley, M.D., Lisa Nyberg, M.D., G. Mani Subramanian, M.D., Ph.D., Robert H. Hyland, D.Phil., Sarah Arterburn, M.S., Deyuan Jiang, Ph.D., John McNally, Ph.D., Diana Brainard, M.D., William T. Symonds, Pharm.D., John G. McHutchison, M.D., Aasim M. Sheikh, M.D., Zobair Younossi, M.D., M.P.H., and Edward J. Gane, M.D. N Engl J Med 2013; 368: May 16, 2013DOI: /NEJMoa

25 Within the next year (US)

26 The future Interferon free Pan-genotypic Minimal side effects Single tablet regimens Effective in difficult to treat groups Prior non responders HIV co-infection Post transplant Cirrhotic 95% SVR in all groups

27 Summary Significant improvements to HCV Rx More effective Minimal side effects Short duration Simple regimens

28 Questions.