hepatitis c treatment in the direct acting antiviral...

Hepatitis C Treatment in the Direct Acting

Antiviral Era - The Pharmacist’s Role

R. Andy Rathbun PharmD, AAHIVP

HCV / HIV / ID Ambulatory Care Pharmacist

Kaiser Permanente, San Diego

2

Disclosure

Clinical investigator with research grants funded by Gilead Sciences, AbbVie, Merck, and Intercept Pharmaceuticals

All grants paid to institution only

3

Learning Objectives

1) Describe the natural history and health burden of hepatitis C

2) Evaluate the current recommendations and treatment options available for hepatitis C

3) Identify areas in which pharmacists can play a significant role in hepatitis C care

4) Develop a basic understanding of what hepatitis C care will look like in the future

4

Discovered in 1989 Previously known as Non-A / Non-B hepatitis

Blood-borne virus that causes inflammation of the liver Disease severity varies between mild short-lived illness to serious lifelong infection

HCV resides in the cytoplasm of hepatocytes Does not integrate into host DNA, unlike HIV Ability to achieve cure

Hepatitis C Virus (HCV)

Rice CM. Top Antivir Med 2011; 19(3):117-20 5

Image Source (Accessed September 12, 2016): http://admin2.aidsbg.info/upload/a111/hcv.jpg

Single-strand, enveloped, positive-sense RNA virus, ~60nm in size

High genetic diversity Error-prone HCV RNA-Polymerase High replication rate (100 to 3,000-fold greater than HIV) > 1 trillion viral particles produced per day

HCV Viral Kinetics

Neuman AU, et al. Science 1998; 282(5386):103-7Schooley RT. Top Antivir Med 2014; 21(5):148-15 6

Image Source (Accessed September 12, 2016): http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-c/images/hep-c-fig1.jpg

If a patient’s daily HCV production was laid end-to-end, how many lengths of a football field would it span?

Trivia Question

7

Image Source (Accessed September 12, 2016): http://clipartix.com/wp-content/uploads/2016/07/Football-field-materials-free-clip-art.png

6 Main Genotypes (GT) with greater than 50 subtypes Influences treatment response Variable disease progression (Increased with GT 3) Geographic distribution

Distribution of genotypes in Northern California Kaiser (> 10,000 patients)

HCV Classification

GT 1 GT 2 GT 3 GT 4 GT 5 GT 6

70% 16% 12% 1% < 1% 1%

Manos MM, et al. J Med Virol 2012; 84(11):1744-50 8

3.2 million (1% to 1.5%) US persons living with HCV ~50 to 75% are undiagnosed

Baby boomers (birth 1945-1965) account for 75% of infections 5x greater risk of HCV infection Majority of these HCV infections occurred in 1970’s and 80’s

Epidemiology of Chronic HCV

MMWR 2012;61(No. RR-4)9

Image Source (Accessed September 12, 2016): https://encrypted-tbn1.gstatic.com/images?q=tbn:ANd9GcTE6RbIutqXCdN2qaL5L8c8LBO1_UzirStQRIBqpiX1y8SxED0R

HCV causes inflammation and injury to the liver Result of which is the progression of fibrosis (essentially scarring)

METAVIR scoring for liver fibrosis F0 to F4 categorization F0 = No fibrosis F4 = Cirrhosis

HCV as a Cause of Liver Damage

Naggie S. Top Antivir Med 2012; 20(5):154-161Sherman KE. Top Antivir Med 2011; 19(3):121-125 10

Image Source (Accessed September 12, 2016): http://baby-boomer-depot.com/wp-content/uploads/2012/09/Stages-of-Liver-deterioration-with-Hepatitis.jpg

Natural History and Progression of HCV

75 – 85%

20 - 30%

2 - 7% per year

11Image Source (Accessed September 12, 2016): Used with permission of Hepatitis C Online (Copyright © 2016 Hepatitis C Online – AWS)http://www.hepatitisc.uw.edu/pdf/evaluation-staging-monitoring/natural-history/core-concept/all

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Risk of Accelerated Fibrosis

Factors Associated With Accelerated Fibrosis Progression

Host Factors

Non-modifiable Fibrosis stage Inflammation grade Older age at time of infection Male sex Organ Transplant

Modifiable Alcohol consumption Nonalcoholic fatty liver disease Obesity Insulin resistance

Viral Factors

HCV genotype 3 Coinfection with hepatitis B virus or HIV

AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Last Updated July 6, 2016. Date Accessed September 12, 2016.

Portal hypertension

Ascites

Encephalopathy

Variceal bleeding

Coagulopathy

Spontaneous bacterial peritonitis (SBP)

Hepatocellular carcinoma (HCC)

Hepatorenal syndrome

Hepatic hydrothorax

Complications of Cirrhosis

Sherman KE. Top Antivir Med 2011; 19(3):121-125 13

Image Source (Accessed September 12, 2016): http://en.wikipedia.org/wiki/File:Hepaticfailure.jpg

Extrahepatic Manifestations

Hematological B-Cell Non-Hodgkin’s Lymphoma Thrombocytopenia Mixed cryoglobulinemia

Dermatological Lichen planus Porphyria cutanea tarda Pruritus

Endocrine Disorders Thyroid disease Type II Diabetes

Central Nervous System Depression Weakness / myalgia Peripheral neuropathy

Rheumatologic Disorders Polyarthralgia Systemic Lupus Erythematosus Sjogren’s syndrome

Renal Glomerulonephritis Nephrotic Syndrome

Zignego AL, et al. Intern Emerg Med 2012; 7(Suppl 7):S201-208Jacobson IM, et al. Clin Gastroenterol Hepatol 2010; 8:1017-1029 14

Image Source (Accessed September 12, 2016): http://mddk.com/wp-content/uploads/2014/07/porphyria-cutanea-tarda-2.jpgImage Source (Accessed September 12, 2016): http://en.wikipedia.org/wiki/File:Cryoglobulinemia2.jpg

HCV is the leading cause of: Cirrhosis HCC Liver transplantation Liver-related deaths

From 2003 to 2013 HCV-associated deaths surpassed 60 other nationally notifiable infectious diseases combined

People with chronic HCV live on average 15 years less than people without HCV

Chronic HCV: Silent but Deadly

15Chhawal J, et al. Hepatology 2016 [Epub ahead of print; Accessed: 9/10/16]Ly KN, et al. Clin Infect Dis 2016;62(10):1287-8Mahajan R, et al. Clin Infect Dis 2014;58(8):1055-61

16

HCV-Associated Advanced Disease Outcomes

320,000

157,000203,000

32,000

587,000

305,000

468,000

53,000

776,000

415,000

665,000

65,000

0

100,000

200,000

300,000

400,000

500,000

600,000

700,000

800,000

900,000

Liver-related Deaths HCC Decompensated Cirrhosis Liver Transplants

All Oral DAA PEG/RBV No Treatment

Nu

mb

er

of

Pat

ien

ts

Projected Cumulative Incidence (2015 to 2050)

Chhawal J, et al. Hepatology 2016 [Epub ahead of print; Accessed: 9/10/16]

$0

$50,000

$100,000

$150,000

$200,000

$250,000

$300,000

No Chronic HCV HCV Non-Cirrhotic

HCVCompensated

Cirrhosis

HCVDecompensated

Cirrhosis

HCV HCC HCV LiverTransplant

$5,676 $19,596 $22,620 $40,320

$94,848

$259,068

Annual Healthcare Costs Between Non-HCV and Chronic HCV Patients

17

Economic Burden of Chronic HCVA

nn

ual

He

alth

care

Co

sts

Walker DR, et al. J Hepatol 2015;62 (Suppl):S593-594

GOALS OF THERAPY AND TREATMENT RECOMMENDATIONS

18

Virologic cure Sustained Virologic Response (SVR) = No HCV detected 12 weeks after treatment completion

Health-benefits of achieving SVR 70% risk reduction for liver cancer 90% risk reduction in liver transplant and liver-related mortality Improvement in all-cause mortality and liver-related health adverse consequences Reduced mortality related to extrahepatic manifestations

Goals of HCV Treatment

van der Meer, et al. JAMA 2012;308(24):2584-2593McCombs, et al. JAMA Intern Med 2014;174(2):204-212Morgan, et al. Ann Intern Med 2013;158(5):329-337

19

WHO Everyone with chronic HCV Exception = Short-life expectancy

Considerations in timing Extrahepatic manifestations Advanced liver disease Higher risk of accelerated fibrosis progression Earlier the better (Early fibrosis stages) Reduce risk of transmission

20

HCV Treatment: Who and When

Pharmacy Directors in charge of the medication budget may want to cover their ears

Image Source (Accessed September 12, 2016): http://images.popmatters.com/misc_art/b/brottman-monkeyear-splsh.jpg


1991 - 2011

interferon (IFN)

peginterferon(PEG)

ribavirin (RBV)

FDA Approved HCV Agents

2011 - 2013

NS3/4A Protease Inhibitor (PI)

boceprevir(BOC)

telaprevir(TVR)

2013 - 2014

NS3/4A Protease Inhibitor (PI)

simeprevir(SMV)

NS5B Polymerase Inhibitor

sofosbuvir(SOF)

2014 - 2015

NS5A Inhibitor

daclatasvir(DCV)

Combination DAA’s

ledipasvir/ sofosbuvir(LDV/SOF)

paritaprevir / ritonavir / ombitasvir+ dasabuvir(PrOD)

paritaprevir / ritonavir / ombitasvir(PrO)

2016

Combination DAA’s

PrOD Extended Release (XR)

sofosbuvir/ velpatasvir(SOF/VEL)

elbasvir/ grazoprevir(EBR/GZR)

21AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Last Updated July 6, 2016. Date Accessed September 12, 2016.

0

10

20

30

40

50

60

70

80

90

100

IFN (24) IFN (48) IFN/RBV(24)

IFN/RBV(48)

PEG (48) PEG/RBV(48)

PI +PEG/RBV(24-48)

DAA +PEG/RBV(12-48)

All OralDAA (8-24)

SVR

(%

)

1991

1998

2011

History of HCV Treatment Response2013 - Present

2001

22

Treatment (Duration = Weeks)

Figure Adapted from the US Food and Drug Administration, Antiviral Drugs Advisory Committee Meeting, April 27-28, 2011, Silver Spring, MD.AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Last Updated July 6, 2016. Date Accessed September 12, 2016.

NS3/4A Protease Inhibitor NS5B Polymerase Inhibitors NS5A Inhibitors

First GenerationSecond

GenerationNucleoside/ Nucleotide

Non-NucleosideFirst

GenerationSecond

Generation

DAA Agentstelaprevirboceprevir

simeprevirparitaprevirgrazoprevir

sofosbuvir dasabuvirledipasvirdaclatasvirombitasvir

elbasvirvelpatasvir

PangenotypicCoverage

Barrierto Resistance

Antiviral Potency

DAA Class Properties

Good Profile Average Profile Least Favorable Profile

Majumdar A, et al. Aliment Pharmacol Ther 2016; 43: 1276-1292Scheel TKH, Rice CM. Nat Med 2013; 19(7):837-849 23

AASLD / IDSA National Guidelines

Factors influencing selection of recommended regimens Efficacy Treatment history Extent of liver disease Genotype Resistance Associated Variants (RAVs) Drug Interactions Patient comorbidities Side effect profile

Treatment Regimen Recommendations


AASLD / IDSA Recommended Regimens

RegimenGenotype

1a 1b 2 3 4 5 6

elbasvir / grazoprevir X X X

ledipasvir / sofosbuvir X X X X X

PrOD ± ribavirin X^ X

PrO + ribavirin X

simeprevir + sofosbuvir X X

sofosbuvir / velpatasvir X X X X X X X

daclatasvir + sofosbuvir X X X

^ RBV included


RegimenGenotype (GT)

(1a / 1b)Non-

CirrhoticCompensated

CirrhosisTreatment

Length (Weeks)

elbasvir / grazoprevir GT1a / GT1b + + 12

ledipasvir / sofosbuvir ± RBV GT1a / GT1b + + 8 - 12

PrOD + RBV GT1a only + - 12

PrOD GT1b only + + 12

simeprevir + sofosbuvir GT1a / GT1b + - 12

sofosbuvir / velpatasvir GT1a / GT1b + + 12

daclatasvir + sofosbuvir GT1a / GT1b + - 12

AASLD / IDSA RecommendationsTreatment Naïve & Previous PEG/RBV Failure (Genotype 1)

elbasvir / grazoprevir - GT 1a check for baseline NS5A RAVs, if present, consider alternative treatment or lengthen treatment to 16 weeks with Ribavirin ledipasvir / sofosbuvir - Alternative regimen of 8 weeks treatment duration in non-cirrhotic patients with baseline HCV viral load < 6 million copies ledipasvir / sofosbuvir + ribavirin used in Genotype 1a and 1b patients with cirrhosis and previous failure to PEG / RBV


Regimen Genotype (s)Non-Cirrhotic Compensated Cirrhosis Treatment

LengthNaïve PEG/RBV Naïve PEG/RBV

sofosbuvir / velpatasvir 2, 3, 4, 5, and 6 + + + + 12 weeks

daclatasvir + sofosbuvir 3 + + - - 12 weeks

daclatasvir + sofosbuvir ± RBV 3 - - + + 24 weeks

PrO + RBV 4 + + + + 12 weeks

elbasvir / grazoprevir 4 + + + + 12 to 16 weeks

ledipasvir / sofosbuvir 4 + + + + 12 weeks

ledipasvir / sofosbuvir 5, 6 + + + + 12 weeks

AASLD / IDSA RecommendationsTreatment Naïve & Previous PEG/RBV Failure (Genotypes 2-6)

Baseline RAV testing in GT 3 non-cirrhotic, treatment experienced and compensated cirrhotic, treatment naïve patients. If Y93H RAV present add Ribavirin to regimen Ribavirin addition to regimen in GT 3 compensated cirrhotic, treatment experienced patients and in GT 4 (same population) using ledipasvir / sofosbuvir For GT 4 patients using elbasvir / grazoprevir extend duration to 16 weeks and add RBV in previous PEG/RBV experienced patients with on-treatment virologic failure


RegimenTreatment Length

Non-cirrhotic Compensated Cirrhosis

Genotype 1

ledipasvir / sofosbuvir + RBV 12 weeks 24 weeks

Genotype 2

daclatasvir + sofosbuvir ± RBV 24 weeks 24 weeks

sofosbuvir / velpatasvir + RBV 12 weeks 12 weeks

Genotype 3

daclatasvir + sofosbuvir + RBV 24 weeks 24 weeks

sofosbuvir / velpatasvir + RBV 12 weeks 12 weeks

AASLD / IDSA RecommendationsRetreatment Previous SOF + RBV ± PEG Failures


AASLD / IDSA RecommendationsRetreatment Previous Protease Inhibitor + PEG/RBV Failures

RegimenTreatment Length

Non-cirrhotic Compensated Cirrhosis

Genotype 1

ledipasvir / sofosbuvir + RBV 12 weeks 12 weeks

ledipasvir / sofosbuvir N/A 24 weeks

sofosbuvir / velpatasvir 12 weeks 12 weeks

daclatasvir + sofosbuvir ± RBV 12 weeks 24 weeks

elbasvir / grazoprevir + RBV 12 – 16 weeks 12 - 16 weeks

29

Previous Protease Inhibitors = telaprevir, boceprevir, simeprevir elbasvir / grazoprevir extend duration to 16 weeks in previous PEG/RBV experienced patients with on-treatment virologic failure


Previous simeprevir + sofosbuvir OR NS5A Inhibitor containing regimens (GT1)

Defer treatment = Non-cirrhotic and no other reasons for urgent treatment

Consideration for retreatment in cirrhosis or other reason for urgent treatment RAV Testing for both NS3/4A Protease Inhibitor and NS5A Inhibitors

30

AASLD / IDSA RecommendationsRetreatment Regimens Containing Multiple DAAs


RegimenDecompensated

CirrhosisSevere Renal Impairment

(CrCl < 30 mL/min)Recurrent HCV Post-Liver

Transplantation

elbasvir / grazoprevir No Yes N/A

ledipasvir / sofosbuvir Yes No Genotypes 1 and 4

PrOD ± ribavirin No Yes Alternative

simeprevir + sofosbuvir No No Alternative

sofosbuvir / velpatasvir Yes No N/A

daclatasvir + sofosbuvir Yes No Genotypes 1, 2, 3 and 4

sofosbuvir + ribavirin No No Genotype 2

AASLD / IDSA RecommendationsRenal, Decompensated Cirrhosis & Post-Liver Transplant

31

Decompensated cirrhosis and recurrent HCV post-liver transplantation: RBV eligible - Add RBV x 12 weeks / RBV ineligible - No RBV x 24 weeks PrOD is recommended in severe renal impairment for GT 1b and as an alternative with RBV in GT 1a Sofosbuvir + ribavirin is the preferred option in RBV eligible patients with GT 2 post-liver transplant recurrent HCV infection and decompensated cirrhosis


AASLD / IDSA RecommendationsHIV/HCV Coinfection

Priority population for treatment◦ Increased risk of liver disease progression

SVR rates similar to HCV monoinfected

Do not interrupt HIV treatment◦ PrO and PrOD use only for patients on HIV therapy◦ Stable on HIV therapy for 1 month before starting

HCV DAA(s) Antiretroviral Drug Interactions

daclatasvirEfaverinz; Etravirine; Nevirapine;

Cobicistat; Atazanavir boosted-ritonavir

elbasvir/ grazoprevirEfaverinz; Etravirine; Nevirapine;

Protease Inhibitors; Cobicistat

sofosbuvir/ velpatasvirEfaverinz,Etravirine, Nevirapine

Regimens containing TDF

ledipasvir/ sofosbuvir Regimens containing TDF

PrODEfaverinz; Etravirine; Nevirapine; Rilpivirine; Cobicistat; Darunavir

simeprevirEfaverinz; Etravirine; Nevirapine;

Protease Inhibitors; Cobicistat


3- 10 tabs total daily scheduled Qday or BID

• PrO + RBV

• PrOD ± RBV

• PrOD XR ± RBV

2 tabs Qday

daclatasvir + sofosbuvir

simeprevir + sofosbuvir

1 tab Qday

• elbasvir / grazoprevir

• ledipasvir / sofosbuvir

• sofosbuvir / velpatasvir

Pill Burden and Administration

With Food Without Regards to Food

33Reference – Individual medication package insert (available on reference slide)

Warnings and Precautions

Serious Symptomatic Bradychardia

• Amiodarone with sofosbuvir and ledipasvir, velpatasvir, simeprevir, or daclatasvir

Hepatic Decompensation and Hepatic Failure (Moderate / Severe Hepatic Impairment)

• Not Recommended: simeprevir / Contraindicated: PrOD, PrOD XR, PrO, elbasvir/grazoprevir

ALT Elevations

• PrOD, PrOD XR, PrO, elbasvir/grazoprevir

Photosensitivity / Rash / Sulfa Allergy

• simeprevir


Common Adverse Events

Insomnia*, Asthenia*,GI related

Fatigue, Headache

Insomnia, pruritus,skinreactions, GI related

N/A

< 10% incidence

> 10% incidence

< 10% Incidence

> 10% Incidence


Ribavirin Warnings and Side Effects

Black Box Warning

Cardiac Events

Pregnancy Category X

More Common

Anemia Fatigue Nausea Pruritus Insomnia Headache

Less Common

AstheniaSkin

ReactionsIrritability Myalgia


Drug Interactions

P-glycoprotein

Acid Soluble

CYP3A4 inducers

OATP1B13 Inhibitors

P-glycoprotein

CYP3A4

CYP3A4

CYP2C8SOF/LDVSOF/VEL

EBR/GZR

DCV + SOFSMV + SOF

PrO & PrOD

Incr

easi

ng

AmiodaroneAnticonvulsants

AntimycobacterialsSt. John’s Wort

DigoxinStatins


PHARMACIST ’S INVOLVEMENT

38

Pharmacist’s Primary Responsibilities Treatment referral review Patient treatment scheduling Patient education visit to review treatment plan Follow up on treatment Treatment outcomes

HEPATITIS C CLINICPharmacists R. Andy Rathbun, Lubna Kazi, Chrislynn Chew, Cindy NgoMDs Heather Patton, Mamie Dong, Lisa Nyberg, Anders NybergPAs Debbie Muratet, Brian FarbRN Coordinators Joyce Kreutzberg, Beth WaltersLVN Julita DioquinoSupport Coordinator RaChae TudaraPharmacy Leadership Jennigrace Bautista, Lina Delosreyes

Clinic Team

39

Pretreatment Evaluation

Medical history Previous HCV treatment / response Liver disease staging Transplant status Drug interaction evaluation

Treatment Readiness Comorbidities Adherence to care Substance abuse Coverage, expected costs, and financial

assistance

Labs (within 12 weeks of treatment) CBC, INR, AST, ALT, total and direct

bilirubin, ALK Phos, Scr and calculated CrCL HIV serology Hepatitis A and B serology (Immunization) HCV genotype / subtype (anytime) Quantitative HCV viral load Pregnancy testing RAV testing as appropriate Substance abuse panel as appropriate


Regular clinic visits and/or telephone contact Adherence; Adverse Events; Drug Interactions

Labs including HCV viral load after week 4 and as appropriate

Early Discontinuation On-treatment virologic failure Drug specific recommendations for monitoring of liver toxicity or decompensation

elbasvir / grazoprevir PrO and PrOD based regimens

Monitoring During Treatment


Monitoring of cirrhosis, regardless of treatment response HCC screening every 6 months Endoscopic esophageal varices screening

Failed to achieve SVR Disease progression assessment every 6 to 12 months Continued evaluation of retreatment appropriateness

Achieved SVR No advanced fibrosis = No additional follow up necessary

Monitoring After Treatment Completion


EBR/GZR

SOF/VEL

PrO

PrOD

LDV/SOF

DCV + SOF

SMV + SOF

Regimen Cost

$54,600

$74,760

$76,608

$83,328

$94,500

$147,000

$150,360

43Information used with permission of Hepatitis C Online (Copyright © 2016 Hepatitis C Online – AWS)http://www.hepatitisc.uw.edu/pdf/evaluation-treatment/cost-access-medications/core-concept/all (Accessed September 12, 2016)

Wholesale Acquisition Cost (WAC) treatment range $54,600 to >$300,000

Average national negotiated discount from WAC 2014 = 22% 2015 = 46%

Numerous cost-effective analysis demonstrate Increased quality-adjusted life expectancy (QALY) Cost-effectiveness in early and late-stage HCV disease

44

Financial Considerations

Linas. Top Antivir Med 2016;24(2):93-97AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Last Updated July 6, 2016. Date Accessed September 12, 2016.

Formulary Restrictions

Reviewing expected co-pay with patient before treatment

Patient co-pay assistance Manufacturer programs Patient Access Network Foundation Patient Advocate Foundation (Co-Pay Relief)

45

Patient Affordability

Pharmacist Optimizing Care

Treatment evaluation Financial considerations Readiness to start treatment Regimen selection

Patient education Side effects, Drug interactions, Medication

administration

Treatment monitoring Safety, Adherence, Effectiveness

46

Image Source (Accessed September 12, 2016): https://upload.wikimedia.org/wikipedia/commons/thumb/a/a7/PharmacistsMortar.svg/2000px-PharmacistsMortar.svg.png

FUTURE OF HEPATITIS C

47

48

In Pursuit of “Perfectovir”

Pangenotypic Activity

SVR > 95%

1 pill Qday

Affordability

Special Populations

Minimal ToxicityDecompensated

Cirrhosis Short Duration

HCV Resistance

Retreatment Options Drug

Interactions

Treatment Needs MetRoom for Improvement

Dore GJ, et al. Clin Infect Dis 2015; 60(12): 1829-36

Investigational Agents

Drug Class

DosingEstimated

AvailabilityComments

ABT-493 + ABT-530NS3/4A PI +

NS5APO Qday 2017

Pangenotypic Potential for 8 wk treatment course Renal Impairment Retreatment

sofosbuvir + velpatasvir + voxilaprevir (GS-9857)

NS5B +NS5A +

NS3/4A PIPO Qday 2017 / 2018

Pangenotypic Potential for 8 wk treatment course Retreatment

MK-3682 + grazoprevir + (elbasvir OR MK-8408)

NS5B + NS3/4A PI +

NS5APO Qday 2018

Pangenotypic Potential for 8 wk treatment course

49

Investigational Agents – DAA Pipeline

Poordad F, et al. EASL 2016. Abstract GS11Kwo PY, et al. EASL 2016. Abstract LBO1Poordad F, et al. EASL 2016. Abstract SAT-157

Lawitz E, et al. EASL 2016. Abstract PS008 Gane EJ, et al. EASL 2016. Abstract SAT-138Gane EJ, et al. EASL 2016. Abstract 139

HCV is a chronic liver disease with potential long-term health implications

Treatment options are now available for almost every patient, offering much improved cure rates, with better tolerability and ease of use

Multiple treatment options will be available over the coming years that should increase access to cure and reduce treatment cost

Fiscal responsibility through quality optimization

Summary

50

What percentage of patients would be expected to develop cirrhosis after 20 to 30 years of being infected with chronic HCV?a) 5%

b) 25%

c) 50%

d) 75%

Test Question 1

51

Which FDA approved HCV regimen has an 8 week treatment duration as an alternative option available for some patients?a) sofosbuvir / ledipasvir

b) daclatasvir + sofosbuvir

c) elbasvir / grazoprevir

d) sofosbuvir / velpatasvir

Test Question 2

52

Which of the following options would be expected to have reduced efficacy when co-administered with omeprazole 40mg twice daily? a) paritaprevir / ritonavir / ombitasvir+ dasabuvir

b) daclatasvir + sofosbuvir

c) elbasvir / grazoprevir

d) sofosbuvir / velpatasvir

Test Question 3

53

1) Rice CM. Top Antivir Med 2011; 19(3):117-202) Neuman AU, et al. Science 1998; 282(5386):103-73) Schooley RT. Top Antivir Med 2014; 21(5):148-154) Manos MM, et al. J Med Virol 2012; 84(11):1744-505) MMWR 2012;61(No. RR-4)6) Naggie S. Top Antivir Med 2012; 20(5):154-1617) Sherman KE. Top Antivir Med 2011; 19(3):121-1258) Hepatitis C Online – AWS: http://www.hepatitisc.uw.edu/pdf/evaluation-staging-monitoring/natural-history/core-concept/all (Accessed September 12, 2016)9) AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Last Updated July 6, 2016. Date Accessed September

12, 201610) Zignego AL, et al. Intern Emerg Med 2012; 7(Suppl 7):S201-20811) Jacobson IM, et al. Clin Gastroenterol Hepatol 2010; 8:1017-102912) Chhawal J, et al. Hepatology 2016 [Epub ahead of print; Accessed: 9/10/16]13) Ly KN, et al. Clin Infect Dis 2016;62(10):1287-814) Mahajan R, et al. Clin Infect Dis 2014;58(8):1055-6115) Walker DR, et al. J Hepatol 2015;62 (Suppl):S593-59416) van der Meer, et al. JAMA 2012;308(24):2584-259317) McCombs, et al. JAMA Intern Med 2014;174(2):204-21218) Morgan, et al. Ann Intern Med 2013;158(5):329-33719) Figure Adapted from the US Food and Drug Administration, Antiviral Drugs Advisory Committee Meeting, April 27-28, 2011, Silver Spring, MD.20) Majumdar A, et al. Aliment Pharmacol Ther 2016; 43: 1276-1292

References

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1. Write down the course code. Space has been provided in the daily program-at-a-glance sections of your program book.

2. To claim credit: Go to www.cshp.org/cpe before December 1, 2016.

Session Code:

hepatitis c treatment in the direct acting antiviral...

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