5 th Paris Hepatitis Congress Workshop 30/1/2012 Managing complications of DAAs: Case 1 Dr Samuel S. Lee University of Calgary.

Slides:

Advertisements

Similar presentations

Optimal therapy in genotype 2 and 3 patients Antonio Craxì Liver & GI Unit, Di.Bi.M.I.S., University of Palermo, Italy

Advertisements

Hepatitis web study Hepatitis web study Simeprevir in Genotype 1 (Viral Relapsers) PROMISE Trial Phase 3 Treatment Experienced Forns X, et al. Gastroenterology.

TWH LIVER CENTRE UHN centre of excellence A case study: Hepatitis C treatment and severe anemia Colina Yim RN(EC), MN Nurse Practitioner CAHN 2013.

Edited by Morris Sherman MD BCh PhD FRCP(C) Associate Professor of Medicine University of Toronto Protease Inhibitors in Chronic Hepatitis C: An Update.

Hepatitis web study Hepatitis web study Sofosbuvir + Peginterferon + Ribavirin in Genotype 2 or 3 LONESTAR-2 Phase 2 Treatment Experienced Lawitz E, et.

Hepatitis web study Hepatitis web study Telaprevir in Treatment Experienced GT-1 REALIZE (Study 216) Phase 3 Treatment Experienced Zeuzem S, et al. N Engl.

Hepatitis web study Hepatitis web study Telaprevir in Treatment Naïve GT-1 ADVANCE (Study 108) Phase 3 Treatment Naïve Jacobson IM, et. al. N Engl J Med.

Hepatitis web study Hepatitis web study Hepatitis web study Hepatitis web study Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir + RBV in GT1 SAPPHIRE-I.

Hepatitis web study Hepatitis web study Simeprevir + PEG + RBV in Treatment-Naïve Genotype 1 QUEST-1 Trial Phase 3 Treatment Naïve Jacobson IM, et al.

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir in Treatment-Experienced GT1 with Cirrhosis SIRIUS Phase 2 Treatment Experienced Bourliere.

Hepatitis web study Hepatitis web study 3D (Paritaprevir-Ritonavir-Ombitasvir + Dasabuvir) + RBV in GT1 SAPPHIRE-I Phase 3 Treatment Naïve Feld JJ, et.

Slide 1 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. IAS–USA Marion G. Peters, MD John V. Carbone, MD, Endowed Chair Professor.

Hepatitis C for the General Practitioner Morris Sherman MB BCh PhD FRCP(C) University of Toronto January 2013.

How to optimize the treatment of HCV-4 patients? Nabil Antaki MD, FRCPC Aleppo, Syria Paris, January 30, 2012.

Hepatitis C Virus Infection Hepatitis C Virus Infection Burden of Disease in United States New infections (cases)/year , ,000 Persons.

Hepatitis web study Hepatitis web study Boceprevir in Treatment Experienced RESPOND-2 Phase 3 Treatment Experienced Bacon BR, et al. N Engl J Med. 2011;364:

Edited by Morris Sherman MD BCh PhD FRCP(C) Associate Professor of Medicine University of Toronto Protease Inhibitors in Chronic Hepatitis C: An Update.

Hepatitis web study Hepatitis web study Telaprevir BID versus q8 in Treatment Naïve GT-1 OPTIMIZE (Study C211) Phase 3 Treatment Naïve Buti M, et al. Gastroenterology.

ATOMIC  Design  Objective –SVR 24 by ITT-analysis, detection of a 30% or 25% difference between two treatment groups, 2-sided significance level of 5%,

Alessio Aghemo First Division of Gastroenterology Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico Università degli Studi di Milano 5 th Paris.

LDV/SOF 90/400 mg qd Non-randomised Open-label N = 21 W12 SVR 12 NIAID SYNERGY GT4 Kohli A. Lancet Infect Dis 2015; Juky 15, ePub ahead of print ≥ 18 years.

ELECTRON  Design SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ELECTRON Study: SOF-based therapy for genotypes 1, 2 and 3 W8W4W12 ≥ 19 years Chronic.

No prior therapy with PI

COSMOS SOF + SMV + RBV SOF + SMV Randomisation 2 : 1 : 2 : 1* Open-label * Randomisation was stratified on genotype (1a or 1b) in both cohorts, IL28B in.

Maria Buti Hospital General Universitario Vall Hebron Barcelona-. Spain Relapser or Non Responder? Chronic Hepatitis C.

How to manage G1 relapsers and non-responders George V. Papatheodoridis, MD Associate Professor in Medicine & Gastroenterology 2nd Department of Internal.

FISSION  Design  Objective –Non inferiority of SOF + RBV : SVR 12 (2-sided significance level of 5%, lower margin of the 95% CI for the difference =

AI Study  Design SOF 1W then DCV + SOF 23W DVC + SOF Randomisation* 1 : 1 : 1 Open-label AI Study: DCV + SOF + RBV for genotypes 1, 2 and.

Reddy KR. Lancet Infect Dis. 2015;15:27-35 ATTAIN SMV + TVR placebo + PEG-IFN + RBV TVR + SMV placebo + PEG-IFN + RBV Randomisation* 1 : 1 Double-blind.

Placebo + PR W48 Placebo + PR Yes Hezode C. Gut 2015;64: COMMAND-1 COMMAND-1 Study: daclatasvir + PEG-IFN + RBV for genotype 1 or 4 DCV60 + PEG-IFN.

Hepatitis-2015 Orlando, USA July

Clinical case Laurent CASTERA 5th PHC, Paris, January Service d’Hépatologie Hôpital Beaujon, Université Paris-7, Clichy, France.

W24 ≥ 18 years Chronic HCV infection Genotype 1 Treatment naïve Early fibrosis to compensated cirrhosis No HBV or HIV co-infection N = 10 SOF + weight-based.

SOLAR-2 LDV/SOF + RBV Randomisation of the 7 groups 1 : 1 Open-label SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype.

SOF/VEL 400/100 mg qd N = 75 W24 SOF/VEL > 18 years Chronic HCV infection Genotype 1 to 6 Naïve or treatment-experienced No prior treatment with NS5A or.

No randomization N = 59 W12W24 Arm B : compensated cirrhosis N = 31 N = 29 Arm C : compensated cirrhosis Arm A : No cirrhosis AGATE-II Study: OBV/PTV/r.

SMV + DCV + SOF Open label Chronic HCV infection Genotype 1 or 4 Treatment-naïve or pre-treated with PEG-IFN ± RBV Portal hypertension or liver decompensation.

Hepatitis web study Hepatitis web study Sofosbuvir + Peginterferon + Ribavirin in Genotype 2 or 3 LONESTAR-2 Phase 2 Treatment Experienced Lawitz E, et.

Triple Therapy Today Phase III Results in G1 Relapsers and Non Responders – Telaprevir 5 th Paris Hepatitis Conference Paris, 30. January 2012 Stefan Zeuzem.

Asselah T. AASLD 2015, Abs. 714 Randomisation 1:1 Open-label years HCV genotype 4 HCV RNA ≥ 1,000 IU/ml Naïve or pre-treated with PEG-IFN + RBV (Part.

OBV/PTV/r + DSV Open label Chronic HCV infection Genotype 1 Treatment-naïve HCV RNA > 1,000 IU/ml Chronic kidney disease with eGFR < 30 ml/min/1.73m 2.

No randomisation Open-label years HCV genotype 1 Naïve or null-response to PEG-IFN + RBV HCV RNA > 10,000 IU/ml No cirrhosis No HBV or HIV co-infection.

Asselah T. AASLD 2015, Abs OSIRIS  Design SMV + PEG-IFN + RBV Open label Chronic HCV infection Genotype 4 Treatment-naïve Mild to moderate fibrosis.

 Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, next observation carried backward DCV + SOF + RBV Randomised* 1:1 Open-label ALLY-3+ study: DCV.

 Objective –SVR 12 (HCV RNA < 25 IU/ml), by ITT OBV/PTV/r + DSV + SOF +RBV Open-label W24 ≥ 18 years Chronic HCV Genotype 1 Prior failure on DAA-regimen.

CASE 1 54 yo man HIV positive 8 yrs ago Tenofovir/FTC/RTV/Atazanavir x 4 yrs Previously documented NNRTI resistance with Y181C, G190A,and mixed m184v/wt.

36 year old HCV+ woman, Risk factor: occasional IVDU 15 years ago First treatment with PEG-IFN/RBV in 2002 –only qualitative PCR available : positive at.

‘Easy to treat’? Graham R Foster Professor of Hepatology Queen Marys University of London.

Hadziyannis SJ et al. EASL Peginterferon alfa-2a (40KD) (PEGASYS ® ) in combination with ribavirin (RBV): efficacy and safety results from a phase.

 Objective –SVR 12 (HCV RNA < 25 IU/ml), by ITT OBV/PTV/r + SOF + RBV OBV/PTV/r + SOF Not randomised Open-label QUARTZ-II Study: OBV/PTV/r + SOF for HCV.

Design Randomisation * 1 : 1 Open-label W16 W24 > 18 years

Design Randomisation 1 : 1 Double-blind W8 W12

No HBV or HIV co-infection

TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1

Design No randomisation Open-label W12 W years HCV genotype 1

ARV-trial.com C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II Randomisation.

GEODE-II Study: OBV/PTV/r + DSV + low dose RBV in genotype 1a

No cirrhosis or compensated cirrhosis** No HBV or HIV co-infection

AL study: AL ODV + SMV in naïve patients, phase II

Creatinine clearance ≥ 50 ml/min No HBV or HIV co-infection

Phase 3 Treatment-Naïve and Treatment-Experienced

ARV-trial.com RUBY-I Study, cohort 2: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for HCV genotype 1 with renal impairment Design Open label W12.

QUARTZ II-III : OBV/PTV/r + SOF RBV in genotype 2 or 3

(Treatment Failure Trial)

ARV-trial.com IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease Design Open label ≥ 18 years Chronic HCV infection Genotype.

GS-US Study: SOF/VEL + GS-9857 in genotype 1 - Phase II

Phase 3 Treatment-Naïve and Treatment-Experienced

CONCERTO-4 Study: SMV + PEG-IFNa-2b + RBV for genotype 1

ENDURANCE-4 Study: glecaprevir/pibrentasvir in genotype 4, 5 or 6

Sequencing cohorts Open-label Design W8 W12 ≥ 18 years

Presentation transcript:

5 th Paris Hepatitis Congress Workshop 30/1/2012 Managing complications of DAAs: Case 1 Dr Samuel S. Lee University of Calgary

Case 1 51 year old Caucasian man HCV discovered 2009 on routine examination Remote history of injection drug use age 19 No symptoms Alcohol: 8-10 beers/week, mostly on weekends Smokes 3-4 cigarettes/d; occasional marijuana asymptomatic

Case 1 Physical exam: weight 81kg, BMI 28 few spider nevi, but no other abnormalities Labs: ALT 2 x N Bilirubin, PT-INR, albumin, N Hb 151 g/L, WBC 7.1, ANC 2.9, plts 145 Ultrasound: coarse liver echotexture – fatty liver? Borderline splenomegaly. No ascites

Case 1: further investigations and course HCV genotype 1a 1.1 million IU/mL HCV RNA (2009) Fibroscan: 10.2 kP (stage 3?) Liver biopsy (from 2009): moderate activity, grade 1, bridging fibrosis, stage F3 No previous treatment – patient did not wish to suffer side effects Had heard of ‘new treatment’ and wished to proceed with triple-Rx

Case 1: treatment Started triple-Rx with PEG a-2a + RBV 1200mg/d + boceprevir 800mg tid (after 4-wk lead-in) Qual HCV RNA detectable at wk 4 lead-in (no RVR) Wk 8 and 12 RNA undetectable Hb 118, ANC 1.2, plts 101 after lead-in Moderate fatigue, flu-like symptoms

Case 1: course Wk 6: Hb 101, ANC 0.9 RBV decreased to 800mg/d Wk 8: Hb 93; fatigue worsening ANC 0.7 RBV decreased to 600mg/d; PEG decreased to 135ug Wk 10: Hb 94, ANC 0,8 Wk 12: Hb 92, ANC 0.7 Wk 16: Hb 89, ANC 0.9; patient working at 60%

Case 1: further course Wk 7: metallic taste in mouth. Pt advised to take plenty of water, small frequent meals Wk 10: still slight dysgeusia but improved Weight loss 5kg by wk 16 Currently at wk 24, stable at PEG 135, RBV 600mg, boceprevir. In view of suspected cirrhosis and drug reductions, plan to continue Rx for 48wk

AE summary Flamm et al. AASLD 2011

Anemia AEs Flamm et al. AASLD 2011

Neutropenia AEs