Download Terry Box, MD - Ogden Surgical

Chronic Hepatitis C and
Project ECHO
State of Affairs
Spring 2013
68th Annual
Terry Box, MD
Disclosures
• Research funding:
– Abbott, Boehringer-Ingelheim, Bristol
Meyers Squibb, Gilead, Idenix, Merck,
Roche, Salix, Sundise
• Speaker’s Bureau:
– Genentech, Merck, Salix, Vertex
• Consultant:
– Kadmon
Hepatitis C Virus Infection
Magnitude of the Problem
• Nearly 4 million persons in United States
infected
• Approximately 35,000 new cases yearly
• 85% of new cases become chronic
• Leading cause of




Chronic liver disease
Cirrhosis
Liver cancer
Liver transplantation
Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at:
http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.
Glossary of Terms
• Viral Load- quantity of virus present in blood
– Measured by assay of HCV RNA by polymerase
chain reaction (PCR)
• Genotype- different types of HCV virions (think
of cousins) identified as 1,2,3,4,5,6
– Subtypes (think of siblings)- 1a,1b,2a,2b,3a,3b
• Response to treatment
– SVR- Sustained Virologic Response
– Relapse and Breakthrough
– Nonresponders- partial and null
Hepatitis C Virus
Genotypes in the USA
Type 2
17%
Type 1
72%
McHutchinson JG, et al. N Engl J Med. 1998;339:1485-1492.
Type 3
10%
All others
1%
Determination of HCV Genotype
INNOLiPA Assay
PCR
1a
1b
2a
• HCV genotype
– Best pretreatment
predictor of response
– Determines duration of
therapy
• All patients should have
genotype determined
prior to initiating therapy
Illustration by Mitchell L. Shiffman, MD.
2b
3a
3b
4
5
Why Treat Chronic Hepatitis C?
• The disease
– Common, chronic, and potentially progressive
– Complications are becoming more common[1,2]
• Liver failure, HCC
• The treatment
– Viral cure, or SVR, is achievable
– SVR associated with histologic improvement and gradual
regression of fibrosis[3]
– SVR reduces risk for liver failure and HCC, improves
survival[4,5]
1. Kanwal F, et al. Gastroenterology. 2011;140:1182-1188. 2. Shaw JJ, et al. Expert Rev Gastroenterol
Hepatol. 2011;5:365-370. 3. Poynard T, et al. Gastroenterology. 2002;122:1303-1313. 4. Craxi A, et al.
Clin Liver Dis. 2005;9:329-346. 5. Shiratori Y, et al. Ann Intern Med. 2005;142:105-114.
Milestones in Therapy of Genotype 1
HCV
Direct-acting
antivirals
2011
100
Peginterferon
80
Standard
interferon
60
2001
Ribavirin
70+
1998
55
1991
42
40
34
39
16
20
6
0
IFN
IFN
6 mos
12 mos
IFN/RBV IFN/RBV PegIFN
6 mos
12 mos
PegIFN/
PegIFN/R RBV/
12 mos
BV
DAA
12 mos
Adapted from US FDA Antiviral Drugs Advisory Committee Meeting; April 27-28,
2011; Silver Spring, MD.
Primary Goal of HCV Therapy
• SVR24: undetectable HCV RNA 6 mos after
completion of treatment
– Considered clinical cure
• Measures of improved outcome
– Histologic improvement
• Inflammatory and fibrosis scores
– Portal pressure reduction
– Reduction in clinical complications including
HCC
– Survival
We Understand the Rules of the Game
With IFN-Based Treatment
• Establishing patient candidacy
• Assessing potential drug–drug interactions
• Evaluating likelihood of SVR in treatmentnaive and treatment-experienced patients
• Applying response-guided treatment
algorithms to maximize response and mitigate
treatment failure
• Optimally managing adverse events
For Genotype 2 or 3, PegIFN/RBV
Remains Standard of Care
• Highly effective therapy with higher cure rates
than genotype 1
• 24 wks of therapy is recommended[1,2]
– Some patients (with RVR and low baseline HCV
RNA) may be treated for 16 wks if therapy poorly
tolerated, although relapse rates may be higher[2]
• Future regimens may offer further
improvements, such as
– Shorter durations
– All-oral therapy
– Fewer adverse events
1. Ghany MG, et al. Hepatology. 2011;54:1433-1444. 2. EASL. J Hepatol. 2011;55:245-264.
Two Protease Inhibitors Approved for
GT1 HCV Infection Combined With PR
Protease Inhibitor
Recommendations
Administration
Boceprevir 800 mg TID
(every 7-9 hrs)[1,2]





Naive to previous therapy
Previous treatment failure
Compensated cirrhosis
Response-guided therapy
Take with food
 All patients initiate therapy
with 4-wk pegIFN/RBV
lead-in phase
 After completion of lead-in
phase, boceprevir should
be added to continued
pegIFN/RBV for 24-44 wks
Telaprevir 750 mg TID
(every 7-9 hrs)[2,3]





Naive to previous therapy
Previous treatment failure
Compensated cirrhosis
Response-guided therapy
Take with food (not low fat)
 All patients initiate therapy
with 12-wk period of triple
therapy with telaprevir plus
pegIFN/RBV
 Followed by 12-36 wks of
pegIFN/RBV
1. Boceprevir [US package insert]. July 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444.
3. Telaprevir [US package insert]. October 2012.
Addition of BOC or TVR to PegIFN/RBV
Improves SVR in Genotype 1 Patients
•
BOC and TVR each indicated in combination with pegIFN/RBV for genotype 1 HCV
patients who are previously untreated or who have failed previous therapy
100
PegIFN + RBV
BOC/TVR + pegIFN* + RBV
69-83
SVR (%)
80
63-75
40-59
60
40
38-44
29-40
24-29
20
7-15
5
0
Treatment
Naive[1,2]
Relapsers[3,4]
Partial
Responders[3,4]
Null
Responders[4,5]
*BOC was administered with pegIFN-α2b; TVR was administered with pegIFN-α2a in these trials.
1. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 2. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.
3. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. 4. Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428.
5. Bronowicki JP, et al. EASL 2012. Abstract 11.
Response Guided Therapy
Patients Responding Early Can Achieve High
SVR Rates With Shortened Therapy
 Response-guided therapy: patients who achieve optimal virologic
response at early time points can receive abbreviated therapy without
reducing their chance of SVR
 Patients eligible for RGT
– Boceprevir: noncirrhotic treatment-naive patients, previous relapsers,
and previous partial responders[1,2]
– RGT criterion: must achieve undetectable HCV RNA at Wk 8 (ie, Wk 4 of triple
therapy) and maintain it at Wk 24
– Telaprevir: noncirrhotic treatment-naive patients and previous relapsers*[2,3]
– RGT criterion: must achieve undetectable HCV RNA at Wk 4 of triple therapy
and maintain it at Wk 12
– Pts with cirrhosis are not eligible for RGT and should have 48 weeks of
therapy
*AASLD guidelines state that RGT may be considered with TVR in previous partial responders.
1. Boceprevir [US package insert]. July 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444.
3. Telaprevir [US package insert]. October 2012.
RGT Paradigm With BOC + PegIFN/RBV
in Tx-Naive Patients
 Indicated for all noncirrhotic treatment-naive
HCV RNA
patients
Undetectable < 100 IU/mL
PegIFN/
RBV
0
4
Undetectable
BOC + PegIFN/RBV
8
Early response stop at Wk 28; f/u 24 wks
24
12
28
36
48
HCV RNA
Detectable
< 100 IU/mL
PegIFN/
RBV
0
4
Undetectable
Slow response extend triple therapy
to Wk 36; PR to Wk 48; f/u 24 wks
BOC + PegIFN/RBV
8
12
24
PegIFN/RBV
28
36
Boceprevir [US package insert]. July 2012. Ghany MG, et al. Hepatology. 2011;54:1433-1444.
Boceprevir [EU package insert]. July 2012.
48
RGT With TVR + PegIFN/RBV in TxNaive Patients and Previous Relapsers

Indicated for all noncirrhotic treatment-naive pts and previous relapsers*[1,3]
HCV RNA
Undetectable Undetectable
TVR + PegIFN/RBV
0
4
Undetectable
PegIFN/RBV
12
eRVR stop at Wk 24, f/u 24 wks
24
48
HCV RNA
Undetectable or
Detectable
(≤ 1000 IU/mL) detectable (≤ 1000 IU/mL) Undetectable
TVR + PegIFN/RBV
0
4
No eRVR extend pegIFN/
RBV to Wk 48; f/u 24 wks
PegIFN/RBV
12
24
48
*AASLD guidelines say RGT “may be considered” for previous partial
but package inserts recommend
48 wks of therapy.[1,3]
1. Telaprevir [US package insert]. October 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444.
3. Telaprevir [EU package insert]. March 2012.
responders[2]
Futility Rules for BOC or TVR +
PegIFN/RBV in Tx-Naive and Tx-Exp’d
Pts
 All therapy should be discontinued in patients with the following:
Boceprevir[1,2]
Time Point
Criteria*
Action
Wk 12
HCV RNA ≥ 100 IU/mL
Discontinue all therapy
Wk 24
HCV RNA detectable
Discontinue all therapy
Telaprevir[2,3]
Time Point
Criteria*
Action
Wk 4 or 12
HCV RNA > 1000 IU/mL
Discontinue all therapy
HCV RNA detectable
Discontinue pegIFN/RBV
Wk 24
*Assay should have a lower limit of HCV RNA quantification of ≤ 25 IU/mL and a limit of HCV RNA
detection of approximately 10-15 IU/mL.
1. Boceprevir [US package insert]. July 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444.
3. Telaprevir [US package insert]. October 2012.
Adverse Effects
BOC Plus PegIFN alfa-2b/RBV: Adverse
Events
• Higher rates of anemia, neutropenia, and
dysgeusia in BOC arms vs control
Adverse Event, %
PR48
(n = 467)
BOC + PR RGT/48*
(n = 1225)
Anemia*
30
50
Neutropenia
19
25
Dysgeusia
16
35
*Anemia was managed with RBV reduction and/or epoetin alfa (43% of BOC + PR and 24%
of PR).
Boceprevir [US package insert]. July 2012.
TVR Plus PegIFN alfa-2a/RBV: Adverse
Events
 Higher rates of rash, anemia, and anorectal signs
and symptoms in TVR arms vs control
PR48
(n = 493)
TVR + PR RGT/48*
(n = 1797)
Rash
34
56
Anemia‡
17
36
Anorectal events
7
29
Adverse Event, %
*Pooled results from TVR arms.
†Anemia was managed with RBV dose modification; epoetin alfa was not permitted.
 In most subjects, rash was mild to moderate
– Severe rash in 4%; discontinuation due to rash in 6% of
subjects
Telaprevir [US package insert]. October 2012.
Higher Discontinuation Rates in
Real-World Settings Than in Clinical Trials
40
50
Patients (%)
30
498 GT1 Patients
Evaluated[1]
21
20
40
33[2]
10
30
20
22
18
17
11
10
n/N =
69/
407
89/
407
43/
407
91/
498
21
0
D/C
Before
Wk 12
0
Mild
Disease
Patient
Choice
Wait for
Better
Therapies
174 GT1 Patients Started
TVR-Based Triple Therapy[2]
Started Therapy
58/
174
36/
174
D/C TVR Due to
< 12 wks
AEs
Did Not Start
1. Chen EY, et al. AASLD 2012. Abstract 133. 2. Bichoupan K, et al. AASLD 2012. Abstract 1755.
Both BOC and TVR Have Potential for
Many Drug–Drug Interactions
• BOC
– Strong inhibitor of
CYP3A4/5
– Partly metabolized by
CYP3A4/5
– Potential inhibitor of and
substrate for P-gp
• TVR
– Substrate of CYP3A
– Inhibitor of CYP3A
– Substrate and
inhibitor of P-gp
• Most drug–drug interactions can be overcome
by careful survey of the patient’s medications
and judicious substitutions during HCV
therapy (or just during the period of PI-based
triple therapy)
Medicines That Are Contraindicated With
BOC and TVR
Drug Class*
Contraindicated With BOC[1]
Contraindicated With TVR[2]
Alpha 1-adrenoreceptor
antagonist
Alfuzosin
Alfuzosin
Anticonvulsants
Carbamazepine, phenobarbital,
phenytoin
N/A
Antimycobacterials
Rifampin
Rifampin
Antiretrovirals
EFV, all RTV-boosted PIs
DRV/RTV, FPV/RTV, LPV/RTV
Ergot derivatives
Dihydroergotamine, ergonovine,
ergotamine, methylergonovine
Dihydroergotamine, ergonovine,
ergotamine, methylergonovine
GI motility agents
Cisapride
Cisapride
Herbal products
Hypericum perforatum (St John’s
wort)
Hypericum perforatum
HMG CoA reductase
inhibitors
Lovastatin, simvastatin
Lovastatin, simvastatin
Oral contraceptives
Drospirenone
N/A
Neuroleptic
Pimozide
Pimozide
PDE5 inhibitor
Sildenafil or tadalafil when used for
treatment of pulmonary arterial HTN
Sildenafil or tadalafil when used for
treatment of pulmonary arterial HTN
Sedatives/hypnotics
Triazolam; orally administered
midazolam
Orally administered midazolam,
triazolam
*Studies of drug–drug interactions incomplete.
1. Boceprevir [package insert]. July 2012. 2. Telaprevir [package insert]. October 2012.
Cirrhotic Patients
CUPIC: Interim Analysis of TVR and BOC Use
in Cirrhotic Early Access Program
• Interim results of 455 patients presented at 16-20 wks
– Encouraging virologic responses with triple therapy
• ~ 80% treated with TVR-based therapy had undetectable HCV RNA at
end of 16 wks of ongoing therapy
• ~ 65% treated with BOC-based therapy had undetectable HCV RNA at
Wk 16 of ongoing therapy
– High rate of serious adverse events
• TVR: 48.6%; BOC: 38.4%
– High rate of anemia
• ~ 30% with grade 2 or higher with either drug
– High rate of premature discontinuation
• ~ 25% with either regimen
Hezode C, et al. AASLD 2012. Abstract 51.
Preliminary Real-World Safety Findings:
CUPIC—PIs in Patients With Cirrhosis
Safety Outcome, n (%)
TVR-Based Treatment
(n = 292)
BOC-Based Treatment
(n = 205)
Serious AEs
132 (45.2)
67 (32.7)
Premature discontinuation
 From serious AEs
66 (22.6)
43 (14.7)
54 (26.3)
15 (7.3)
Death*
5 (2.6)
1 (0.5)
Infection (grade 3/4)
19 (6.5)
5 (2.4)
Rash
 Grade 3/SCAR
14 (4.8)
0
Hepatic decompensation
6 (2.0)
6 (2.9)
47 (16.1)
13 (6.3)
Blood transfusions
*Causes of death in patients treated with TVR: septicemia, septic shock, pneumopathy, esophageal
varices bleeding, endocarditis; causes of death in patients treated with BOC: pneumopathy.
Hezode C, et al. EASL 2012. Abstract 8.
Summary
• BOC- or TVR-based triple therapy increases SVR
rates over pegIFN/RBV alone for all genotype 1
patient populations that have been evaluated
• On-treatment management techniques including
application of RGT algorithms and effective
management of adverse events maximize treatment
outcomes and mitigate treatment failure
• In spite of significant progress using BOC- or TVRbased triple therapy there are several challenging
impediments to universal application for HCV patients
Regimens—Many Challenges
For us—lead-in, response-guided therapy . . .
For our patients . . .
Pill Burden
BOC = 12/day
RBV = 4-7/day
Food Requirement
TVR = 6/day
RBV = 4-7/day
Challenges of Current PI-Based Therapy
• Efficacy
– Very dependent on the IFN response
• Tolerability
– Additional AEs beyond pegIFN/RBV
• Regimens
– Complicated (lead-in, RGT)/pill burden
• DDIs
– Many with both agents to common drugs
• Genotype/special populations
– Limited activity in non-GT1, limited data HIV/OLTx, ESRD
Future of HCV Therapy
Dosing and Regimens: Current
Challenges and Future Solutions
Challenge
Investigational Strategies
Dosing burden: 6-12
pills/day (TID dosing) with
PIs + 4-7 pills/day RBV, food
requirements
QD, BID dosing;
elimination of RBV;
fixed-dose combinations; no
food requirements
RGT, lead-in,
variable regimen based on
treatment experience,
up to 48 wks
No RGT;
no pegIFN/RBV lead-in;
shorter regimens
Different therapies based on
HCV genotype
DAA-based regimens
effective across genotypes
IFN containing;
poor tolerability
IFN sparing, alternative IFNs;
agents with fewer adverse
events
What Are the Key Elements of an Ideal
HCV Regimen?
Easy Dosing
Once daily, low pill
burden
Highly Effective
All Oral
High efficacy in
traditionally challenging
populations (ie, poor
IFN sensitivity, cirrhosis)
PegIFN/RBV replaced
with alternate backbone
with low chance of
resistance
Simple Regimen
Short duration, simple,
straightforward
stopping rules
Pan-Genotypic
Regimen can be used
across all genotypes
Safe and Tolerable
Few or easily
manageable adverse
effects
HCV Life Cycle and DAA Targets
Receptor binding
and endocytosis
Transport
and release
Fusion
and
uncoating
Translation
and
polyprotein
processing
NS3/4 protease
inhibitors
ER lumen
(+) RNA
LD
LD
Virion
assembly
LD
Membranous
web
ER lumen
NS5A* inhibitors
*Block replication complex formation, assembly
Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.
NS5B polymerase
RNA
replication
inhibitors
Nucleoside/nucleotide
Nonnucleoside
Investigational Agents for HCV
Interferons
Antiviral
agents
Therapeutic
vaccines
Host
target
miRNA-122
Entry
Replication, polyprotein
processing and/or assembly
NS5B
polymerase
inhibitors
NS3
protease
inhibitors
NS5A
replication
complex
inhibitors
Cyclophilin
Cyp
inhibitors
Comparison of DAA Profiles
DAA
PI, 1st
PI, 2nd
Generation Generation
NS5A Inh
Nuc
NS5B Inh
Resistance
Profile
Pangenotypic
Efficacy
Efficacy
Adverse
Events
Drug–Drug
Interactions
Good profile
Average profile
Adapted from: Farnik H, et al. Antivir Ther. 2012;17:771-783.
Least favorable profile
Nonnuc
NS5B Inh
Investigational HCV Regimens
in Phase III Clinical Trials
Regimens With 1 DAA
+ PegIFN alfa/RBV
 Faldaprevir (BI 201335, PI)
 Daclatasvir (BMS-790052,
NS5A)
 Sofosbuvir (GS-7977, NI)
 Simeprevir (TMC-435, PI)
 Alisporivir (CYP)
 Vaniprevir (MK-7009, PI)
Alternative Dosing
 TVR BID (approved PI)
ClinicalTrials.gov. November 27, 2012.
Regimens With 2 DAAs
+ PegIFN alfa/RBV
IFN-Free Regimens
 Sofosbuvir + RBV
 Sofosbuvir + GS-5885
(NS5A) (FDC) ± RBV
 Asunaprevir (PI) +
New IFNs
daclatasvir
 ABT-450 (PI)/RTV/ABT PegIFN lambda-1a + RBV
267 (NS5A) (FDC) +
 PegIFN lambda-1a +
ABT-333 (NNI) + RBV
daclatasvir + RBV
 Faldaprevir (PI) +
 PegIFN lambda-1a + RBV + BI 207127 (NNI) + RBV
TVR
 Daclatasvir + asunaprevir
Daclatasvir Plus Sofosbuvir ± RBV in
Treatment-Naive GT1 or 2/3 Patients
• No impact of RBV on viral response
SVR24, %
GT1
GT2/3
93
88
Daclatasvir + Sofosbuvir
100
100
Daclatasvir + Sofosbuvir + RBV
100
93
Wk 1
Treatment-naive,
noncirrhotic
patients
GT1a or 1b
(n = 44)
GT2 or 3
(n = 44)
Sofosbuvir
Wk 24
Daclatasvir + Sofosbuvir
Sobosbuvir dosed 400 mg QD. Daclatasvir dosed 60 mg QD. RBV dosed by body weight for
GT1 patients (1000-1200 mg/day); 800 mg/day for GT2/3 patients.
Sulkowski MS, et al. AASLD 2012. Abstract LB-2.
Treat Now vs Wait: Many Issues to
Consider
Treat now
Defer
• Triple therapy increases SVR
• Earlier treatment has higher
success rates
• Successful treatment may
arrest progression of liver
disease
• Uncertainty about timelines
for approval and
reimbursement
•First-generation PIs complex,
associated with adverse events
•Does current treatment failure
affect future treatment?
•Potential for higher SVR,
including in challenging
populations
•Potential for simpler regimens,
QD or BID, fewer adverse
effects, eventually IFN-free
•Activity in non–genotype 1
Advantages of Future Therapies
•
•
•
•
•
•
Once-daily dosing
Shorter duration
Simpler regimens—no RGT
Fewer AEs
IFN free
High efficacy
Caveats to Future Therapies
• Very small studies
• Potential for toxicity remains
– Agents from multiple classes (nucs, nonnucs, PI,
alisporivir) pulled for toxicity
• Efficacy and safety in cirrhosis largely unknown
• Minimal data—DDIs, special populations (OLTx, HIV, ESRD)
• Timelines uncertain
– Not just approval, but availability and reimbursement
• Costs uncertain, but likely an issue in many regions
HIDING IN PLAIN SIGHT
If this stuff is so good, where
are all the patients hiding?
Total No. Infected (millions)
Hepatitis C Virus (HCV) Infection
4
75% Unaware of Infection
3
2
1.1 Million1
~800,000 to 1.4 Million1
21% Unaware of Infection
65% Unaware of Infection
HIV
HBV
1
0
•
•
2.7 to 3.9 Million1
Undiagnosed
Diagnosed
HCV
HCV is approximately 4 times as prevalent as HIV and HBV in the United States
A 2011 study estimated that as many as 5.2 million persons are living with HCV in
the United States2
HCV=hepatitis C virus; HIV=human immunodeficiency virus; HBV=hepatitis B virus.
1. Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: The National Academies
Press; 2010; 2. Chak E, et al. Liver Int. 2011;31(8):1090-101.
You Are the First Line for HCV Screening
2%
(US prevalence of HCV1)
x 2000 patients
(average patient load for PCP2)
Average PCP has
40 patients with HCV
in his/her practice2*
One in 30 baby boomers in the US has HCV (3.25%); however certain
areas have a higher prevalence of the disease.3,4
*Across the country HCV prevalence differs by region, state, and locality.
ALT=alanine aminotransferase; HCV=hepatitis C virus; PCP=primary care provider; OR=odds ratio.
1. Chak E, et al. Liver Int. 2011;31(8):1090-101; 2. Ferrante JM, et al. Fam Med. 2008;40(5):345-351; 3. Smith BD, et al. Abstract #394. Presented at: American
Association for the Study of Liver Disease 2011 Annual Meeting; San Francisco, CA; November 5, 2011; 4. Institute of Medicine. Washington, DC: The National
Academies Press; 2010.
Chronic HCV Infection May Result in Liver
Cirrhosis, HCC, and Liver-Related Death
Fibrosis
Cirrhosis
Hepatocellular Carcinoma
(with cirrhosis)
Liver transplant
•
HCV is the #1 cause of liver transplant in
the United States1
•
Up to 45% of patients awaiting liver
transplant have HCV2
Liver cancer
•
HCV is the leading cause of HCC1
Death
•
4% annual death rate postcirrhosis3
•
CDC has identified the number of deaths
from HCV now exceed those from HIV4
The rate of progression of liver fibrosis accelerates as fibrosis advances
and can vary from patient to patient5,6
HCV = hepatitis C virus; HCC = hepatocellular carcinoma.
1. Rustgi VK. J Gastroenterol. 2007;42(7):513-21; 2. Gringeri E, et al. Transplant Proc. 2007;39(6):1901-1903; 3. Sangiovanni A, et al. Hepatology. 2006;43(6):1303-10. 4. The
Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 243. Presented November 8, 2011. 5. Thein HH, Yi Q, Dore
GJ, et al. Hepatology. 2008;48(2):418-31. 6. Missiha SB, et al. Gastroenterology. 2008;134(6):1699–714.
Although the Peak of Infections Occurred Decades Ago, Complications
From HCV Will Continue to Increase as Chronic HCV Progresses
Number of Patients
1,200,00
0
1,000,0
00
800,00
0
600,00
0
400,00
0
200,00
0
0
25%
of patients with HCV
currently have cirrhosis
37%
of patients with HCV are projected
to develop cirrhosis by 2020,
peaking at 1 million
1990
2000
2010
Year
2020
An estimated 33% of undiagnosed baby boomers with HCV currently have
advanced fibrosis (F3-F4, bridging fibrosis to cirrhosis)1
Adapted from Davis GL, et al. Gastroenterology 2010;138:513-21.
1. McGarry LJ. Hepatology. 2012;55(5):1344-55.
2030
Decrease in Life Expectancy With Chronic HCV Is
Similar to the Decrease Due to Smoking
Life Expectancy (Years)
90
80
8 to 12
year
reduction
13 to 14
year
reduction
HCV
Smoking
1
2
70
60
50
40
0
Average3
HCV=hepatitis C virus.
1. Ryder SD. J Hepatol. 2007;47(1):4-6; 2. Centers for Disease Control and Prevention. MMWR. 2002;51:300-303; 3. Centers for Disease
Control and Prevention. NVSS. 2010;58(19):1-135.
Rates (%)
Studies Have Shown a Decreased Rate of Liver
Complications in Patients Who Achieved SVR With
Peg-IFN/RBV*
20
18
16
14
12
10
8
6
4
2
0
Rates of Liver-Related Complications (%)
Patients With SVR (n=140)
Nonresponders (n=309)
13.9%
11.0%
9.1%
6.8%
1.4%
Decompensated
Liver Disease†
0.7%
Liver
Transplantation
1.4%
HCC
0.7%
Liver-Related
Death
•
The HALT-C Trial was a multicenter study of 1145 subjects with advanced
chronic HCV who were nonresponders to previous IFN-based treatment
•
The trial found that achieving SVR with Peg-IFN/RBV therapy significantly
reduced HCV-associated complications and mortality
*With pegylated interferon alfa and ribavirin; †Decompensated liver disease included variceal hemorrhage, ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy.
HALT-C = Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis; HCC = hepatocellular carcinoma; HCV = hepatitis C virus; IFN = interferon; Peg-IFN = pegylated interferon;
RBV = ribavirin; SVR = sustained virologic response.
Morgan TR, et al. Hepatology. 2010;52(3):833-44.
CDC Guidelines for Screening Baby
Boomers
The Centers for Disease Control and Prevention
(CDC) has created draft guidelines recommending a
one-time anti-HCV antibody test for all baby
boomers (those born from 1945 through 1965) in an
effort to identify these undiagnosed individuals
.
Baby Boomers (Those Born From 1945 Through 1965)
Account for 82% of HCV Cases in the United States1
Estimated Prevalence by Age Group2
Number With Chronic HCV
Infection (millions)
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
<1920
1920s
1930s
1940s
1950s
1960s
1970s
1980s
1990+
Birth Year Group
1.
2.
Smith BD, et al. Hepatology. 2011; 54(4):554A.
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.
Comparison of HCV Cost-Effectiveness
With Other Routine Preventive Services
› According to the National Commission on Prevention Priorities, the cost-effectiveness of HCV testing
of baby boomers would be similar to that of hypertension, HIV testing, and cholesterol screening
60,000
$/QALY
$/QALY
50,000
40,000
30,000
20,000
10,000
0
Colorectal,
Flu,
Hypertension, HCV testing, HIV testing, Cholesterol Breast CA,
aged 50+ aged 50+ aged 18+ 1945-1965 aged 13-64 screening aged 40+
QALY= quality-adjusted life year.
http://www.prevent.org/National-Commission-on-Prevention-Priorities/Rankings-of-Preventive-Services-for-the-US-Population.aspx. Accessed May 23, 2012.
Rein DB, et al. Ann Intern Med. 2012;156:263-70
Summary
•
Up to 5.2 million persons are living with HCV in the United States
•
75% of infected individuals are not aware of their HCV status
•
HCV is a chronic disease and the number of patients estimated to develop
serious liver
outcomes is projected to peak in 2020, reaching over 1 million
.
cases of cirrhosis
•
HCV can be cured in 75% of those treated with today’s medications
•
Special attention should focus on diagnosing and referring populations
disproportionately affected by HCV, as recommended by the updated CDC
guidelines
– 82% of patients with chronic HCV were born from 1945 through 1965
You are at the front line of screening and TREATMENT—
identification is the first step in a patient’s chance for a cure
Transition to Care
Project ECHO
Extension for Community Health Outcomes
An innovative web-based healthcare delivery system developed to
treat chronic and complex diseases in rural and underserved areas
through the use of telemedicine technology.
Terry D. Box, MD Director
Susanne M. Cusick Manager
Objectives
• Enhance the capacity of Community providers to
effectively treat common chronic, complex diseases in
remote and underserved areas
• Bridge the gap between primary providers and
specialist to maximize time and expertise
• Teach and disseminate best practices
• Provide case-based CME to Primary Care clinicians
Objectives-cont.
• Reduce Professional Isolation by providing access to a
multidisciplinary specialty care team
• Expand access to care by sharing medical knowledge
• Target Clinical conditions that are common, require
complex treatment and have impact on health and
economics
– Hepatitis C
– Asthma
Diabetes
Chronic Pain
Child Psychiatry
Rheum. Arthritis
How it Works
• Providers are self-identified/recruited to participate
• At each site a lead clinician (MD, NP, PA) is
identified to become the local expert
• Site Initiation includes visit from the U of U team to
train and assist with tech issues
• Participating providers and staff may visit University
to shadow clinicians
How it Works-cont.
• Weekly web-based “Knowledge Network”
for disease management
• Providers present cases to ECHO faculty who
mentor the local provider
– Proven success:
“Outcomes of Treatment for Hepatitis C Virus Infection by
Primary Care Providers”
Sanjeev Arora, M.D., Karla Thornton, M.D., Glen Murata, M.D., et al.
N Engl J Med 2011; 364:2199-2207 June 9, 2011
• Real-time, case based learning
– CME: Category 1
Capacity and Relationship Building
• Virtual Work Force Multiplier
– Efficient and effective delivery of University Faculty
expertise and outreach
– Collegial interaction with primary providers
• Expertise is developed in primary providers
– who teach co-workers and
– serve as local consultants for peers in the
clinic/region
Project ECHO HCV- Utah
• Launched at the University of Utah in October 2011
• Weekly web-based ECHO clinics held
– 29 different sites have participated
• (From UT, WY, CO, MT and CA)
– More than 150 consultations on 90+ patients
– 18 additional sites awaiting initiation
• Multi-disciplinary ECHO Team present at each
clinic:
– Hepatologist
– Psychiatrist
– Pharm D
Project ECHO- Utah
Opportunity for replication in other diseases
-Faculty mentors identified in the following areas
Child and Adolescent Psychiatry
Inflammatory Bowel Disease
Cognitive Dysfunction in the Aged
Eating Disorders
Solid Organ Transplant
Pain Management
Rheumatoid Arthritis
Chronic Kidney Disease
HIV Treatment
Project ECHO
Primary Care Providers bringing value
driven specialty care to patients and
communities through today’s technology