Developed by Camilla S Graham MD BIDMC 5515 cgrahambidmcharvardedu Slides can be selected or altered as needed Disclosures 75 of People with Hepatitis C in the US are Baby Boomers ID: 362033
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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