Advances in Hepatitis C Identification and Treatment - PowerPoint Presentation

Slide1

Advances in Hepatitis C Identification and Treatment

Developed by Camilla S. Graham, MD, BIDMC, 5/5/15.

cgraham@bidmc.harvard.edu

.

Slides can be selected or altered as needed.Slide2

DisclosuresSlide3

75% of People with Hepatitis C in the US are Baby BoomersSlide4

Identifying Patients with Hepatitis C

4-5 million people in the US have hepatitis C virus (HCV) infection

NHANES estimates 3.2 million infected but this national survey excludes people who do not have a permanent address (homeless, incarcerated, nursing home residents), active military, and under-represents most groups outside White, African-American, and Mexican-Hispanic

Accounting for under-represented international populations, homeless, and groups that have a high prevalence like IDU and veterans gives the 5+ million estimate

Most were infected in 1960’s through 1980’s

Up to 250,000 cases per year in 1980’s

About 50% infected via IDU, rest from blood transfusions, sex, tattoos, medical procedures, and other factors

4

Smith BD et al. MMWR. August 17, 2012/61(RR04);1-18. Armstrong GL et al. Ann Intern Med. 2006 May 16;144(10):705-14.

http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx

; Rein et al. Dig Liver Dis 2011; 43:66Slide5

Identifying Patients with Hepatitis C

Up to 75% of people have not been diagnosed

50% to 75% is estimated

Risk-based screening misses many people

Overburdened primary care

Lack of knowledge for patients and providers

Stigma associated with IDU, even if decades ago

Leading cause for liver transplantation and liver cancer (HCC)

37% lifetime risk of HCV-related mortality for patients with chronic HCV

5

Smith BD et al. MMWR. August 17, 2012/61(RR04);1-18. Armstrong GL et al. Ann Intern Med. 2006 May 16;144(10):705-14.

http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx

; Rein et al. Dig Liver Dis 2011; 43:66Slide6

Estimates of People with Hepatitis C in Massachusetts

Number People with Reactive anti-HCV Antibody

United

States Census Bureau 2010: Age and Sex Compositions (

http://www.census.gov/prod/cen2010/briefs/c2010br-03.pdf

; accessed

7/23/14);

Ditah

et al. J

Hepatology 2014; 60:691 - NHANES HCV survey found 1.3% prevalence anti-HCV in US population age >18; Chak et al. Liver International 2011; 31:1090 - Adjustment for groups excluded from NHANES including homeless, incarcerated, active military and nursing home residentsUse state-specific data found at http://www.nvhr.org/content/nvhr-hepatitis-c-state-specific-resources-pagesSlide7

Baby Boomers (Born in 1945–1965) Account for 76.5% of HCV in the US

1

7

Estimated Prevalence by Age Group

2

Birth Year Group

0

1.6

1.4

1.2

1.0

0.8

0.6

0.4

0.2

1990+

1980s

1970s

1960s

1950s

1940s

1930s

1920s

<1920

Number with chronic HCV (millions)

An estimated 35% of undiagnosed baby boomers with HCV currently have advanced fibrosis (F3-F4; bridging fibrosis to cirrhosis)

3

1. Centers for Disease Control and Prevention.

MMWR

. 2012;61:1-32; Adapted from Pyenson B, et al.

Consequences of Hepatitis C Virus (HCV): Costs of a baby boomer Epidemic of Liver Disease

. New York, NY: Milliman, Inc; May 18, 2009. http://www.milliman.com/expertise/healthcare/publications/rr/consequences-hepatitis-c-virus-RR05-15-09.php Milliman report was commissioned by Vertex Pharmaceuticals; 3. McGarry LJ et al.

Hepatology.

2012;55(5):1344-1355. Slide8

Who Should Be Tested for HCV

CDC Recommendations

Everyone born from 1945 through 1965 (one-time)

Persons who ever injected illegal drugs

Persons

who

received clotting factor concentrates produced before

1987

C

hronic (long-term) hemodialysisPersons with persistently abnormal ALT levels. Recipients of transfusions or organ transplants prior to 1992Persons with recognized occupational exposuresChildren born to HCV-positive womenHIV positive personsUSPSTF Grade B Recs*Everyone born from 1945 through 1965 (one-time)Past or present injection drug useSex with an IDU; other high-risk sexBlood transfusion prior to 1992Persons with hemophilia

Long-term hemodialysis

Born to an HCV-infected mother

Incarceration

Intranasal drug use

Receiving an unregulated tattoo

Occupational percutaneous exposure

Surgery before implementation of universal precautions

8

*Only pertains to persons with normal liver enzymes; if elevated liver enzymes need HBV and HCV testing

Smith at al. Ann Intern Med 2012; 157:817-822. Moyer et al. Ann Intern Med epub 25 June 2013Slide9

Massachusetts Hepatitis C Testing Law

: Section 138; Chapter

111

Every person born between the years of 1945 and 1965 who receives health care services from a primary care provider shall be offered a hepatitis C screening test or a

hepatitis

C diagnostic test unless the provider believes that: (

i

) the person is being treated for a life threatening emergency; (ii) the person has previously been offered or has received a hepatitis screening test; or (iii) the person lacks capacity to consent to a hepatitis C screening test.

9

http://www.mass.gov/bb/gaa/fy2015/prnt_15/os_15/p138.htmSlide10

Ms. Smith

55 y/o woman followed for 12 years in primary care for anxiety and recently for menopause. Three years ago noted to have ALT 60 after estrogen replacement so switched to transdermal gel and follow up ALT 40.

Presented with URI and found to have

Hgb

9.3 and platelets 81,000. Additional testing showed ALT 36, AST 82, Albumin 2.7, total bilirubin 1.0 and INR 1.2.

10Slide11

Ms. Smith

HCV antibody positiveHCV RNA 16,500Genotype 1a

11Slide12

Ms. Smith

CT abdomen with nodular liver, spleen 13.8 cm and small amount of ascitesEGD with two grade 1 esophageal

varices

Hepatic encephalopathy?

12Slide13

Ms. Smith

Only possible “risk exposure” was foot surgery at a free-standing podiatry clinic in 1982

13Slide14

Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer

14

Fibrosis

1

Chronic HCV infection can lead to the development of fibrous scar tissue within the liver

Fibrosis

Cirrhosis

Hepatocellular Carcinoma

(with cirrhosis)

Cirrhosis

1,2

Over time, fibrosis can progress, causing severe scarring of the liver, restricted blood flow, impaired liver function, and eventually liver failure

HCC

3

Cancer of the liver can develop after years of chronic HCV infection

Chronic liver disease includes fibrosis, cirrhosis, and hepatic decompensation; HCC=hepatocellular carcinoma.

1. Highleyman L. Hepatitis C Support Project. http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Fibrosis.pdf. Accessed August 18, 2011; 2. Bataller R et al.

J Clin Invest

. 2005;115:209-218;

3. Medline Plus. http://www.nlm.nih.gov/medlineplus/enxy.article/000280.htm. Accessed August 28, 2012; 4. Centers for Disease Control and Prevention. http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm. Accessed May 8, 2012.

Decompensated cirrhosis:

Ascites

Bleeding

gastroesophageal

varices

Hepatic encephalopathy

JaundiceSlide15

Deaths Due to HCV Infections Now Exceed

Those Due to HIV Infection

16,600 deaths

Ly KN, Xing J, Klevens RM,

Jiles

RB, Holmberg SD. Causes of death and characteristics of decedents with viral hepatitis, United States, 2010.

Clin

Infect Dis.

2014 Jan;58(1):40-9. Mahajan, IDSA 2013

Number of HCV-related deaths may be over 60,000 because of under-reporting on death

certificatesSlide16

Projected Numbers of Decompensated Cirrhosis and Cases of HCC to Rise Through 2020Slide17

Median interval: 3 years

Median age: 53 years

76,122 HCV diagnoses were reported to the MDPH between 1992 and 2009, 8,499 of these reported HCV cases died and are represented in the figure. Data as of 1/11/2011.

Timing of Mortality

A

mong

K

nown HCV Cases in Massachusetts, 1992-2009

Lijewski

, et al, 2012

17Slide18

Screening of Baby Boomers May Prevent >120,000 Deaths Due to HCV Infection

Birth-cohort screening in primary care would identify 86% of all undiagnosed cases in the birth cohort, compared with 21% under risk based screening

1

Cost effectiveness of HCV screening is comparable to cervical cancer or cholesterol screening (cost/QALY gained with protease

inhibitor+IFN+RBV

= $35,700)

Markov chain Monte Carol simulation model of prevalence of hepatitis C antibody stratified by age, sex, race/ethnicity, history of injection drug use, and natural history of chronic hepatitis C.

*With pegylated interferon and ribavirin plus DAA treatment.

†

Deaths due to decompensated cirrhosis or hepatocellular carcinoma within 1945-1965 birth cohort. 470,000 deaths under birth cohort screening vs 592,000 deaths under risk-based screening

1. Rein D et al

. Ann Intern Med.

2012;156(4):263-270; 2. McGarry LJ et al.

Hepatology.

2012;55(5):1344-1355.

18Slide19

Efficient Identification of Hepatitis C in a Health Care Setting

19Slide20

BIDMC/CareGroup Experience

Network of academic hospitals, primary care practices, community health centers that share a common electronic medical record system

5,500 clinicians and ~1.5 million patients

Implemented a prompt in EMR for a one-time anti-HCV test in all patients born from 1945-1965 who had no prior record of testing, while continuing risk-based testing

Went live on June 4, 2013

In the first ten months, we tested a total of 20,000 people for HCVSlide21

Steps to Implement Birth Cohort HCV Testing

Build a core team: Primary

Care, Infectious Disease,

Hepatology

, Database Management, and

Clinical Pathology

I

mplement

a one-time electronic prompt for anti-HCV antibody testing for all patients born from 1945 through 1965 who have no record of HCV antibody testing One-page educational tool for providers and one for patients (samples at KNOW MORE HEPATITIS/CDC and NVHR.org)

Email notification to affected cliniciansHCV nurse educator Help facilitate patient referral in the Liver Center and Infectious Diseases ClinicSlide deck for presentations to primary care providers about HCV (sample at NVHR.org) Collaboration with Laboratory Services Expand capacity for increased volume of HCV Ab and RNA tests Add language to results page (or a second prompt) for all positive HCV antibody tests informing clinicians to order an HCV RNA test to determine the presence of active HCV infectionGenerates a report of all positive HCV antibody tests for follow upSlide22

Examples of screen shots for HCV baby boomer testing prompts can be found at

http://nvhr.org/programSlide23

Initial Hepatitis C Testing and Evaluation

Who Should Be Tested for Hepatitis C?

New: Anyone born between 1945 and 1965 should be tested once, regardless of risk factors

In addition, patients with the following risk factors:

Elevated ALT (even intermittently)

A history of illicit injection drug use or intranasal cocaine use (even once)

Needle stick or mucosal exposure to blood

Current sexual partners of HCV infected persons

Received blood/organs before 1992

Received clotting factors made before 1987

Chronic hemodialysis

Infection with HIV

Children born to HCV-infected mothers

Why Test People Born Between 1945-1965?

76% of the ~4 million people with HCV infection in the US are baby boomers

In the 1945-1965 cohort:

All: 1 out of 30

Men: 1 out of 23

African American men: 1 out of 12

Up to 75% do not know they have HCV

73% of HCV-related deaths are in baby boomers

What Can Happen to People with Hepatitis C?

It is important to identify if patients have cirrhosis

Patients with cirrhosis are at risk for liver cancer (HCC) and liver

decompensation

(ascites,

variceal

bleed, hepatic encephalopathy, jaundice)

Hepatitis C is curable, and cure reduces the risk of severe complications, even with cirrhosis

Refer patients to a specialist who has experience treating hepatitis C to see if they need treatment

Counsel Patients with HCV Infection About Reducing Risk of Transmission

Do not donate blood, body organs, other tissue, or semen

Do not share personal items that might have small amounts of blood (toothbrushes, razors, nail-grooming equipment, needles) and cover cuts and wounds

HCV is not spread by hugging, kissing, food or water, sharing utensils, or casual contact

If in short term or multiple relationships, use latex condoms. No condom use is recommended for long-term monogamous couples (risk of transmission is very low)

1

Example

ICD-9 codes for HCV antibody testing: V73.89: screening for other specified viral disease

790.4: nonspecific elevation of levels of transaminase; use if patient ever had an elevated ALT

Initial ManagementEvaluate alcohol use (CAGE, AUDIT-C) and recommend stopping use Vaccinate for hepatitis A and hepatitis B if not previously exposed

Evaluate sources of support (social, emotional, financial) needed for HCV treatment

Smith BD et al. MMWR. August 17, 2012/61(RR04); 1-18. Adapted from Winston et al. Management of hepatitis C by the primary care provider: Monitoring guidelines; 2010; http://www.hcvadvocate.org/hepatitis/factsheets_pdf/PCP_web_10.pdf

Hepatitis C Antibody (HCV

Ab

)

1

Positive (+)

Check HCV RNA (viral load)

Positive (+)

Hepatitis C infection

Evaluation and referral

Negative (-)

STOP here if no concern for acute infection or severe immunosuppression. If so, check HCV RNA.

Negative (-)

These people are NOT chronically infected.

Detectable HCV

Ab

with negative HCV RNA can occur with spontaneous clearance of infection ( about 25% of people exposed to HCV will clear; verify HCV RNA negative in 4 to 6 months) or with treatment of HCV.

23Slide24

PCP Education Example: Screening in Clinic

1,000 adult patients

330 baby boomers

10 HCV antibody positive

7 HCV RNA positive

3 with more advanced fibrosis

4 with mild fibrosis

Efficiently identify birth cohort 1945-1965:

Electronic prompt

~1/3 of adults are in 1945-1965 cohort

1 of 30 baby boomers

1 of 23 men baby boomers

1 of 12 African American men baby boomers

15%-30% of HCV antibody patients will spontaneously clear

Up to 25% of baby boomers may have

cirrhosis

75% of cirrhotic patients are men

Davis, Gastro 2010; 138: 513

24Slide25

Number of HCV Antibody Tests Performed In Four Week Intervals

Beth Israel Deaconess Medical Center, Boston, MA, Quality Outcomes Data, 1/22/14Slide26

HCV Antibody Test Volume Increased after EMR Prompt

Beth Israel Deaconess Medical Center, Boston, MA, Quality Outcomes Data,

6/5/14Slide27

More Women Tested for HCV but More Men are Anti-HCV Positive

Group

Number (%) Tested for HCV Ab

Anti-HCV

Seroprevalence

(%)

All Boomers

13,107

2.3%

Boomer women7,555 (58%)1.4% (34% of HCV Ab+ results)Boomer men5,552 (42%)3.6% (66% of HCV Ab+ results)All Non-Boomer7,0222.6%Non-Boomer women4,023 (57%)1.9% (42% of HCV Ab+ results)Non-Boomer men2,999 (43%)3.5% (58% of HCV Ab+ results)Beth Israel Deaconess Medical Center, Boston, MA, Quality Outcomes Data, 6/5/14Slide28

Initial Approach to Patients Diagnosed with Hepatitis CSlide29

Hepatitis C Diagnosis has been Made: What to Discuss with the Patient

Do not donate blood. May donate organs to others with HCV

Do not share personal items that might have small amounts of blood

Toothbrushes, razors, nail-grooming equipment

HCV is not spread by hugging, kissing, food or water, sharing utensils, or casual contact

If using illicit drugs, stop using. If continued, get into a treatment program and do not share needles, syringes or works

Concern among payers about poor adherence and reinfection after antiviral Rx

If in short term, multiple or MSM relationships, use latex condoms. No condom use is recommended for long-term monogamous heterosexual couples

Maximum incidence rate of HCV sexual transmission estimated about 1 new infection per 190,000 sexual contacts per year (Terrault

, Hepatology. 2013; 57(3):881)Limit Tylenol to 2 gm a day and discuss all other medications (including OTC and herbal ) with a providerCheck exposure status for hepatitis A and B and vaccinate if needed

Adapted from Winston et al. Management of hepatitis C by the primary care provider: Monitoring guidelines; 2010 http://www.hcvadvocate.org/hepatitis/factsheets_pdf/PCP_web_10.pdf Slide30

Address Alcohol Use in HCV

The CDC recommends brief alcohol intervention for all patients with HCV

There is no “safe” amount of alcohol consumption

Insist on absolute abstinence if patient has bridging fibrosis or cirrhosis

Assess for risky alcohol use

Men: >2 drinks/day (>14/week) or more that 4 in one day

Women: >1 drink/day (>7/week) or more than 3 in one day

Screen for alcohol misuse

How many times in the past year have you had X or more drinks in a day?”, where X is 5 for men and 4 for women, and a response of >1 is considered positive

30

http://www.integration.samhsa.gov/images/res/tool_auditc.pdf

Moyer et al. Screening and Behavioral Counseling Interventions in Primary Care to Reduce Alcohol Misuse: USPSTF Recommendation Statement. Annals Int Med; 14 May 2013 onlineSlide31

Baseline Labs in Patients with Newly Diagnosed HCV

HCV RNA “viral load” (determines active infection)

Hepatitis C genotype (determines treatment choice)

Complete blood count (platelets <150,000

assc

with cirrhosis)

INR, Albumin, Total bilirubin (abnormal liver synthetic function often indicates advanced liver disease)

Creatinine, Glucose, ALT, AST, Alkaline Phosphatase

Hepatitis A serology: total or IgG (vaccinate if nonreactive)Hepatitis B serology:

HBsAb, HBcAb, HBsAg (vaccinate if all nonreactive)HIV antibodyIron studies, ANAAssessment of liver fibrosis (such as Hepascore, Fibrotest, APRI, FIB-4, Fibroscan)

31

BIDMC HCV ECHO Program Recommendations, 2014Slide32

Distribution of Fibrosis Scores

F0 = 15%F1 = 25%F2 = 20%

F3 = 15%

F4 = 25%

Limits of fibrosis tests:

Liver biopsies are +/- 1 fibrosis stage

Noninvasive tests are best at determining a high versus low probability of advanced fibrosis

32

“

Advanced fibrosisRecently infected and slow progressorsSlide33

Determine Likelihood of

Cirrhosis

N

oninvasive test results increase

the likelihood of cirrhosis, especially if more than one are

present:

APRI >1.5 or FIB-4 >3.25 (use on-line calculators

)

FIB-4 more predictive of ESLD than liver biopsy (CROI 2014)Hepascore or Fibrotest >0.74Fibroscan >12.5

Platelets <150,000Albumin < 3.5Splenomegaly on exam or ultrasoundAny signs of liver decompensation MELD and Child-Pugh scores (use on-line calculators)Chou, Annals Int Med 2013; 158:807; Bonder, Curr Gastro Rep 2014; 16:372; Berenguer #640 and Lo Re #650 CROI 2014Slide34

FibroScan - Transient

Elastography

Ultrasound determines velocity of shear wave in m/s, which is proportional to liver stiffness in kilopascal (

kPa

)

Entire process requires 15 to 20 minutes, provides immediate results

Falsely elevated results:

High ALT (>100)

Eating within 2 hours

ALV 10.7.13

Bonder,

Curr

Gastro Rep 2014; 16:372Slide35

Continuum of Fibrosis/Cirrhosis in HCV

Continuum of scores (in

kPa

)

<7 kPa = Stage 0-1

7-9.5

kPa

= Stage

2

9.5-12.5

kPa

= Stage

3

>

12.5

kPa

= Cirrhosis

>20 kPa = Increased risk liver-related complications

70+ kPa

Bonder,

Curr

Gastro Rep 2014; 16:372Slide36

Management of Patients with Hepatitis C and Cirrhosis

Every 6 month screening for liver cancer

Usually ultrasound

Consider CT or MRI if highly nodular liver; first exam

Screening for esophageal varices

Repeat every 1 -3 years depending on results

Counsel on symptoms of hepatic encephalopathy

Vaccination for pneumococcus

Counseling around medication use to avoid overdose or adverse events (including common drugs like Tylenol and NSAIDS)

Counseling about complete abstinence from alcoholEvaluation for antiviral treatmentCure of HCV can reduce liver failure and liver cancer, even in patients with cirrhosis (+/- HIV coinfection)Possible referral for liver transplant services36

http://www.aasld.org/practiceguidelines/pages/guidelinelisting.aspx Slide37

SVR (Cure) Associated with Decreased All-Cause Mortality

10-year Cumulative Incidence Rate

530 patients with advanced fibrosis, treated with interferon-based therapy, and followed for 8.4 (IQR 6.4-1.4) years

Van der Meer et al. JAMA 2012; 308:2584

8.9

26

5.1

21.8

2.1

29.9Slide38

Recent Treatment Data and GuidelinesSlide39

The World is Rapidly Changing in HCV

Pegylated

interferon (Peg-IFN) + ribavirin (RBV)

Peg-IFN + RBV +

Telaprevir

Peg-IFN + RBV +

Boceprevir

Peg-IFN + RBV +

Simeprevir

Sofosbuvir+Ledipasvir x 8 weeksParitaprevir/r/ombitasvir+dasabuvir+/-RBV x 12 weeks Sofosbuvir +RBV x 12 weeksSofosbuvir+Ledipasvir x 12 weeksSofosbuvir+Simeprevir x 12 weeksParitaprevir/r/ombitasvir+dasabuvir+/-RBV x 24 weeks (geno 1a cirrhotic [F3-F4] null [non-] responders?)Sofosbuvir+RBV x 24 weeksSofosbuvir+Ledipasvir x 24 weeks

Sofosbuvir+RBV

x 48 weeksSlide40

SVR in Genotype 1, Naïve, Non-cirrhotic Patients Treated with

Sofosbuvir+Ledipasvir (ION-3)

Percent SVR

Harvoni

package insert, 10/11/14

119/123

83/92

126/131

82/85

90%

96%

96%

97%

40Slide41

Key Points with Sofosbuvir+Ledipasvir

Most common AEs are fatigue and headache

Taken with or without food

Ledipasvir

needs acid for solubility/absorption

Be careful with OTC acid blockers (TUMS, Rolaids, Mylanta, calcium supplements, as well as proton pump and H2)

eGFR

>30 mL/min/1.73m

2 No dose adjustment for Child-Pugh Class A, B, or C cirrhosisPregnancy Class BAvoid P-gp inducers; see all other DDI data in PI

Harvoni package insert, 10/11/1441Slide42

SVR-12 in Genotype 1 Patients Treated with

Paritaprevir/

r+Ombitasvir+Dasabuvir

+/- RBV (3-D)

Percent SVR

Naïve, no cirrhosis,

Geno

1b:

Viekira

Pak x12

wks

Naïve, no cirrhosis,

G

eno

1a:

Viekira

Pak+RBV

x12

wks

Naïve, cirrhosis,

G

eno

1a or 1b:

Viekira

Pak+RBV

x12

wks

Peg-IFN/RBV failure,

G

eno

1b:

Viekira

Pak+RBV

x12

wks

Peg-IFN/RBV failure ,

G

eno 1a:Viekira

Pak+RBV x 24 wks (may use 12

wks if relapse, or no cirrhosis)

N=473

N=91

N=297

N=209

N=100

N=208*

Feld; NEJM 2014 Apr 11;

Zeuzem

; NEJM 2014 Apr 10;

Poordad

NEJM 2014 Apr 12Slide43

Compare Key Attributes of Harvoni

vs. Viekira

Pak

Harvoni

Viekira

Pak

SVR

≥

95% with correct duration

SVR ≥92% with correct duration (may have better efficacy in geno 1b)Very well toleratedNeeds monitoring for anemia, dose reduce RBV (<10%)Pts with decompensation and post-Tx need RBV85% of patients need RBVOne pill once a day10 pills a day (if require generic RBV)8 to 12 week duration12 to 24 week durationCan use with Child B and CCannot use with Child B and CCommon DDIs: HIV meds, acid blockersCommon DDIs: HIV meds, Estradiol, fluticasone, salmeterol, some statinsFail with NS5A resistanceFail with 3-drug class resistance

43Slide44

Genotype 2

Sofosbuvir+RBV

x

12 weeks

Naïve, with or without cirrhosis

o

r

Treatment experienced, no cirrhosis

Treatment experienced, with cirrhosis Sofosbuvir+RBV x 12-16 weeks Sofosbuvir+Peg-IFN+RBV x 12 weeks

2014 IDSA/AASLD Recommendations: www.hcvguidelines.orgSlide45

SVR in Genotype 2 Patients Treated with Sofosbuvir+Ribavirin for 12 Weeks

Percent SVR

EASL 2014

Treatment experienced, cirrhotic patients only had a 78% SVR with 16 weeks SOF+LDV. May wait for sofosbuvir + daclatasvir Slide46

Sofosbuvir+RBV

x 24

weeks

Sofosbuvir+Peg-IFN

+

RBV

x

12 weeks Sofosbuvir+Ledipasvir + RBV x 12 weeks? Sofosbuvir+Peg-IFN+RBV x 12 weeksGenotype 3Naïve, with or without cirrhosis

o

r

Treatment experienced, no cirrhosis

Treatment experienced, with cirrhosis

Sofosbuvir+RBV

x 24

weeks

www.hcvguidelines.org

Sofosbuvir+Daclatasvir

(

Compassionate use until FDA approval)Slide47

Hypothetical Costs of

Not Optimizing SVR Rates in Clinical Practice

95%

85%

SVR in clinical trials

SVR in real world

10% difference in SVR rates for a $100,000 regimen result in:

$12,384

“

loss $ per unachieved cure

”

for each patient

Cost of retreating all patients who did not achieve SVR

Costs of liver complications (decompensation, liver cancer, etc.) in those who are not cured and progressSlide48

HCV Treatment Initiation: BIDMC Example

Assess patients for readiness, insurance status, and fill out clinical assessment form

Deliver the

1

st

fill

of medication to provider office only

Require teaching visit with clinical staff prior to starting

treatmentDocument true start date and inform Specialty PharmacySet up ALL follow-up and lab appointments right after teaching visitProvide teaching handout and list of appointments to patientUtilize pill box / blister pack / smart phone reminder apps to enhance medication complianceSpecialty pharmacy with weekly or biweekly phone call to

patients for follow up assessmentAdopt a real time tracking system (ie, TrioHealth)Record patient baseline characteristics and treatment regimenPrompt for wk 4, wk 12 viral load and SVR12 due datesMethod of communication for provider office and specialty pharmacySlide49

Pricing and ReimbursementSlide50

Current Negative

Environment Created By High Price of HCV Drugs

Confusion and doubt among HCV

treaters

Fear from PCPs about testing and

treatment

Fear/outrage among payers (public and private)

Hesitation in DPH/public outreach programs

Questions about integrity of CDC work (research and KNOW MORE HEPATITIS campaign)

Declarations by prisons, state Medicaids that HCV treatment is not of valueDifficulty establishing broad baby boomer testing programsRationing of treatment, ie F3-F4; substance useConflict between provider, patient and payer over rationingNo discussion of cure-as-preventionJustification for overt discriminatory practices like mandating clean urine samplesConfirmation by patients that they are not “worth” treatmentLoss of vision about transformative, curative developmentsSlide51

How did we get into this mess?Slide52

Unique Aspects of Hepatitis C

Relatively common diseaseMajority of people infected 20 – 40 years ago (75% in 1945-1965 birth cohort)

Peak of severe liver complications expected to occur over this next decade, so urgency to identify and treat people soon

Everyone who has >1 year life expectancy is theoretically a treatment candidate

Pricing more similar to treatments for rare diseasesSlide53

Regimen

SVR rates

WAC

Price

Cost

per SVR

Pegasys

+ Ribavirin x 48 weeks

1

41%

$41,758

$101,849

Telaprevir +

PegIFN

+ Ribavirin x 24 weeks

2

75%

$

86,843

$115,791

Sofosbuvir +

PegIFN

+ Ribavirin x 12

weeks

90%

$

94,421

$104,912

Sofosbuvir+Ledipasvir

x 8 weeks

94%

$63,000

$67,021

($36,191?)*

Sofosbuvir

+

Ledipasvir

x 12 weeks

99%

$94,500

$95,454

($51,545?)*

Package inserts for

products;

*http

://blogs.wsj.com/pharmalot/2015/02/04/what-the-shocking-gilead-discounts-on-its-hepatitis-c-drugs-will-mean/

“

Standard of Care

”

Regimens for Hepatitis C Have Been Expensive for Years:

Examples for Treatment of Genotype 1, Naïve, Non-Cirrhotic PatientsSlide54

Cost-Effectiveness of HCV Treatment

Study

Key Findings

Leidner

,

Hepatology

2015

For 55 y/o treated

with $100,000 regimen and SVR = 90%, treating at F2 compared to waiting until F3 had CE = $37,300/QALYThreshold cost for treating at F0 versus waiting until F1 to yield $50,000/QALY = $22,200Rein, CID 2015Harvoni and Viekira Pak compared to no treatment yields $32,000 to $35,000/QALYCompared to no treatment, threshold cost for treating F0 with all-oral regimen = $47,000Najafzadeh, Annals Int Med 2015Compared to no treatment in genotype 1, costs per additional QALY gained for Harvoni = $25,291 and Peg-IRN/RBV = $24,833If Harvoni <$66,000/treatment course, would be cost savingChhatwal, Annals Int Med 2015Average ICER for sofosbuvir-based treatment compared to prior SOC = $55,378/QALYRange = $9,703/QALY for naïve, cirrhotic geno 1 to $410,548 for treatment experienced, geno 3 without cirrhosisSlide55

Payer Dilemmas

Most payers had no idea how much they were actually spending per treated patient (or per cure) in the interferon eraPI/P/R in cirrhotic patients ~ $266,000 per cure

1

Pharmacy budgets often separate from medical budgets

Pharmacy budgets don’t get “credit” for avoidance of medical costs

Annual budgets

“Is it cost effective?” (off-sets over the long term)

“Is it affordable?” (costs over one year)

1

Sethi, AASLD 2013Slide56

Medical Need Restriction

Advanced

f

ibrosis (

Metavir

F3-F4)

Evidenced by liver biopsy, transient elastography,

F

ibrotest, APRI or FIB-4 score, radiological imaging consistent with cirrhosis, physical findings or clinical evidence consistent with cirrhosis as attested by the prescribing physicianSlide57

Response to Restricting Treatment to F3/F4

Cannot require liver biopsy (may be highest risk of death in HCV care with all-oral regimens)

Since no test can perfectly distinguish F2 from F3 or F3 from F4, limiting access to F3/F4 really means directing treatment to cirrhotic patients

If we wait until advanced fibrosis, need to do life-long screening for HCC every six months even if cured (expense, logistics, patient anxiety)

Prioritization of F2-F4 unless other compelling urgency may align with provider capacitySlide58

Community Network in HCV

Community Health Centers

Academic Centers

Private Primary Care Centers

Community Gastroenterology

Departments of Public Health

Patient Advocacy Organizations

Commercial Payers

Government Payers

Pharmaceutical Companies

Prisons

Government Policy Makers

Pharmacies

ECHO

MediaSlide59

Resources

IDSA/AASLD/IAS–USA HCV GuidanceFederal guidelines (VA, prison system)National Viral Hepatitis Roundtable

Collects templates, sample slide presentations, analyses of state and federal policies

Program assistance with 1945-1965 birth cohort testing

www.NVHR.org