Chronic Hepatitis C and Project ECHO State of Affairs Spring 2013
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Transcript of Chronic Hepatitis C and Project ECHO State of Affairs Spring 2013.
Chronic Hepatitis C and Chronic Hepatitis C and Project ECHOProject ECHO
State of Affairs State of Affairs Spring 2013Spring 2013
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 InfectionMagnitude 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 VirusGenotypes in the USA
All others1%
Type 310%
Type 217%
Type 172%
McHutchinson JG, et al. N Engl J Med. 1998;339:1485-1492.
Determination of HCV GenotypeINNOLiPA Assay
• HCV genotype
– Best pretreatment predictor of response
– Determines duration of therapy
• All patients should have genotype determined prior to initiating therapy
PCR1a
1b
3a3b
4
2b
2a
5
Illustration by Mitchell L. Shiffman, MD.
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
Adapted from US FDA Antiviral Drugs Advisory Committee Meeting; April 27-28, 2011; Silver Spring, MD.
SV
R (
%)
IFN
6 mos
PegIFN/R
BV
12 mos
IFN
12 mos
IFN/RBV
12 mos
PegIFN
12 mos
2001
1998
2011
Standardinterferon
Ribavirin
Peginterferon
1991
Direct-actingantivirals
PegIFN/RBV/DAA
IFN/RBV
6 mos
616
3442 39
55
70+
0
20
40
60
80
100
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 treatment-
naive 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
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.
0
20
40
60
80
100
SV
R (
%)
Relapsers[3,4] Partial Responders[3,4]
PegIFN + RBV
NullResponders[4,5]
BOC/TVR + pegIFN* + RBV
24-29
7-15
29-40
5
69-83
40-59
63-75
38-44
Treatment Naive[1,2]
*BOC was administered with pegIFN-α2b; TVR was administered with pegIFN-α2a in these trials.
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
1. Boceprevir [US package insert]. July 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444. 3. Telaprevir [US package insert]. October 2012.
*AASLD guidelines state that RGT may be considered with TVR in previous partial responders.
RGT Paradigm With BOC + PegIFN/RBV in Tx-Naive Patients
Indicated for all noncirrhotic treatment-naive patients
BOC + PegIFN/RBV
480 28124
PegIFN/RBV
8 3624
Early response stop at Wk 28; f/u 24 wks
HCV RNA Undetectable Undetectable
480 28124
PegIFN/RBVPegIFN/RBV
8 36
BOC + PegIFN/RBV
24
Slow response extend triple therapy to Wk 36; PR to Wk 48; f/u 24 wks
< 100 IU/mL
< 100 IU/mL
Boceprevir [US package insert]. July 2012. Ghany MG, et al. Hepatology. 2011;54:1433-1444. Boceprevir [EU package insert]. July 2012.
HCV RNA
Detectable Undetectable
RGT With TVR + PegIFN/RBV in Tx-Naive Patients and Previous Relapsers
TVR + PegIFN/RBV
480 24124
eRVR stop at Wk 24, f/u 24 wksPegIFN/RBV
TVR + PegIFN/RBV
480 24124
PegIFN/RBV
HCV RNAUndetectable
Undetectable
Detectable (≤ 1000 IU/mL)
Undetectable or detectable (≤ 1000 IU/mL)
No eRVR extend pegIFN/ RBV to Wk 48; f/u 24 wks
HCV RNA
Indicated for all noncirrhotic treatment-naive pts and previous relapsers*[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.
Undetectable
Undetectable
*AASLD guidelines say RGT “may be considered” for previous partial responders[2] but package inserts recommend 48 wks of therapy.[1,3]
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:
1. Boceprevir [US package insert]. July 2012. 2. Ghany MG, et al. Hepatology. 2011;54:1433-1444.3. Telaprevir [US package insert]. October 2012.
*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.
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
Wk 24 HCV RNA detectable Discontinue pegIFN/RBV
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
Adverse Event, % PR48 (n = 493)
TVR + PR RGT/48*
(n = 1797)
Rash 34 56
Anemia‡ 17 36
Anorectal events 7 29*Pooled results from TVR arms. †Anemia was managed with RBV dose modification; epoetin alfa was not permitted.
Telaprevir [US package insert]. October 2012.
In most subjects, rash was mild to moderate– Severe rash in 4%; discontinuation due to rash in 6% of
subjects
1. Chen EY, et al. AASLD 2012. Abstract 133. 2. Bichoupan K, et al. AASLD 2012. Abstract 1755.
50
40
30
20
10
0
Pat
ien
ts (
%)
n/N =
18
498 GT1 Patients Evaluated[1]
Started Therapy
2217
1169/407
89/407
43/407
Did Not Start
PatientChoice
Wait forBetter
Therapies
MildDisease
Higher Discontinuation Rates in Real-World Settings Than in Clinical Trials
D/CBeforeWk 12
21
40
30
20
10
0
91/498
D/C TVR < 12 wks
58/174
33[2]
21
36/174
174 GT1 Patients StartedTVR-Based Triple Therapy[2]
Due to AEs
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
• 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)
• TVR– Substrate of CYP3A– Inhibitor of CYP3A– Substrate and
inhibitor of P-gp
Medicines That Are Contraindicated With BOC and TVR
1. Boceprevir [package insert]. July 2012. 2. Telaprevir [package insert]. October 2012.
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.
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.
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)
RashGrade 3/SCAR 14 (4.8) 0
Hepatic decompensation 6 (2.0) 6 (2.9)
Blood transfusions 47 (16.1) 13 (6.3)
Hezode C, et al. EASL 2012. Abstract 8.
*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.
Preliminary Real-World Safety Findings: CUPIC—PIs in Patients With Cirrhosis
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 TVR-based triple therapy there are several challenging impediments to universal application for HCV patients
Regimens—Many Challenges
For us—lead-in, response-guided therapy . . .
BOC = 12/dayRBV = 4-7/day
TVR = 6/dayRBV = 4-7/day
Pill Burden Food RequirementFor our patients . . .
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
RGT, lead-in,variable regimen based on
treatment experience,up to 48 wks
Different therapies based on HCV genotype
QD, BID dosing;elimination of RBV;
fixed-dose combinations; no food requirements
No RGT;no pegIFN/RBV lead-in;
shorter regimens
DAA-based regimens effective across genotypes
IFN containing; poor tolerability
IFN sparing, alternative IFNs; agents with fewer adverse
events
Simple Regimen
Short duration, simple, straightforward stopping rules
What Are the Key Elements of an Ideal HCV Regimen?
Pan-Genotypic
Regimen can be used across all genotypes
Highly Effective
High efficacy in traditionally challenging
populations (ie, poor IFN sensitivity, cirrhosis)
Safe and Tolerable
Few or easily manageable adverse
effects
All Oral
PegIFN/RBV replaced with alternate backbone
with low chance of resistance
Easy Dosing
Once daily, low pill burden
HCV Life Cycle and DAA Targets
Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.
Receptor bindingand endocytosis
Fusion and
uncoating
Transportand release
(+) RNATranslation
andpolyprotein processing
RNA replication
Virionassembly
Membranousweb
ER lumen
LD
LDER lumen
LD
NS3/4 protease inhibitors
NS5B polymerase inhibitors
Nucleoside/nucleotideNonnucleoside
*Block replication complex formation, assembly
NS5A* inhibitors
Investigational Agents for HCV
Interferons Antiviral agents
Therapeuticvaccines
Hosttarget
Replication, polyprotein processing and/or assembly
Entry
NS5Bpolymerase inhibitors
NS3protease inhibitors
NS5Areplication complex inhibitors
miRNA-122 Cyclophilin
Cyp
inhibitors
Comparison of DAA Profiles
DAA
PI, 1stGeneration
PI, 2ndGeneration
NS5A InhNuc
NS5B InhNonnuc
NS5B Inh
Resistance Profile
Pangenotypic Efficacy
Efficacy
Adverse Events
Drug–DrugInteractions
Good profile Average profile Least favorable profile
Adapted from: Farnik H, et al. Antivir Ther. 2012;17:771-783.
Regimens With 1 DAA + PegIFN alfa/RBV
Regimens With 2 DAAs + PegIFN alfa/RBV
IFN-Free Regimens
Faldaprevir (BI 201335, PI) Daclatasvir (BMS-790052,
NS5A) Sofosbuvir (GS-7977, NI) Simeprevir (TMC-435, PI) Alisporivir (CYP)
Vaniprevir (MK-7009, PI)
Daclatasvir + asunaprevir Sofosbuvir + RBV Sofosbuvir + GS-5885
(NS5A) (FDC) ± RBV Asunaprevir (PI) +
daclatasvir ABT-450 (PI)/RTV/ABT-
267 (NS5A) (FDC) + ABT-333 (NNI) + RBV
Faldaprevir (PI) + BI 207127 (NNI) + RBV
Investigational HCV Regimensin Phase III Clinical Trials
New IFNs
PegIFN lambda-1a + RBV PegIFN lambda-1a +
daclatasvir + RBV PegIFN lambda-1a + RBV +
TVR
ClinicalTrials.gov. November 27, 2012.
Alternative Dosing
TVR BID (approved PI)
On Hold
Daclatasvir Plus Sofosbuvir ± RBV in Treatment-Naive GT1 or 2/3 Patients
• No impact of RBV on viral response
Treatment-naive, noncirrhotic
patients
GT1a or 1b (n = 44)
GT2 or 3 (n = 44)
Daclatasvir + SofosbuvirSofosbuvir
Daclatasvir + Sofosbuvir
Daclatasvir + Sofosbuvir + RBV
Wk 1 Wk 24
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.
GT1
93
100
100
GT2/3
88
100
93
SVR24, %
Treat Now vs Wait: Many Issues to Consider
Treat now•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
Defer•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?
Hepatitis C Virus (HCV) Infection
• 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.
Tota
l No.
Infe
cted
(mill
ions
)
DiagnosedUndiagnosed 2.7 to 3.9 Million1
75% Unaware of Infection
1.1 Million1
21% Unaware of Infection~800,000 to 1.4 Million1
65% Unaware of Infection
HIV HBV HCV
4
3
2
1
0
You Are the First Line for HCV Screening
x 2000 patients(average patient load for PCP2)
Average PCP has 40 patients with HCV
in his/her practice2*
2%(US prevalence of HCV1)
One in 30 baby boomers in the US has HCV (3.25%); however certain One in 30 baby boomers in the US has HCV (3.25%); however certain areas have a higher prevalence of the disease.areas have a higher prevalence of the disease.3,43,4
*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.
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.
Chronic HCV Infection May Result in Liver Cirrhosis, HCC, and Liver-Related Death
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
Fibrosis Cirrhosis Hepatocellular Carcinoma
(with cirrhosis)
The rate of progression of liver fibrosis accelerates as fibrosis advancesand can vary from patient to patient5,6
Year
Nu
mb
er o
f P
atie
nts
1,200,000
1,000,000
800,000
600,000
400,000
0
200,000
1990 2000 2010 2020 2030
25%of patients with HCV
currently have cirrhosis
25%of patients with HCV
currently have cirrhosis
37%of patients with HCV are projected
to develop cirrhosis by 2020, peaking at 1 million
37%of patients with HCV are projected
to develop cirrhosis by 2020, peaking at 1 million
Adapted from Davis GL, et al. Gastroenterology 2010;138:513-21. 1. McGarry LJ. Hepatology. 2012;55(5):1344-55.
Although the Peak of Infections Occurred Decades Ago, Complications From HCV Will Continue to Increase as Chronic HCV Progresses
An estimated 33% of undiagnosed baby boomers with HCV currently have advanced fibrosis (F3-F4, bridging fibrosis to cirrhosis)1
SmokingHCV
Decrease in Life Expectancy With Chronic HCV Is Similar to the Decrease Due to Smoking
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.
Lif
e E
xpec
tan
cy (
Yea
rs)
Average30
40
50
60
70
80
90 8 to 12 8 to 12 year year
reductionreduction11
8 to 12 8 to 12 year year
reductionreduction11
13 to 14 13 to 14 year year
reductionreduction22
13 to 14 13 to 14 year year
reductionreduction22
Studies Have Shown a Decreased Rate of Liver Complications in Patients Who Achieved SVR With
Peg-IFN/RBV*
• 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
Rates of Liver-Related Complications (%)
*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.
Patients With SVR (n=140)
Nonresponders (n=309)
DecompensatedLiver Disease†
LiverTransplantation
HCC Liver-RelatedDeath
13.9%
9.1%11.0%
6.8%
02468
101214161820
1.4% 1.4%0.7% 0.7%
Rat
es (
%)
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
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n (m
illio
ns)
Birth Year Group
0
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
1990+1980s1970s1960s1950s1940s1930s1920s<1920
Baby Boomers (Those Born From 1945 Through 1965) Account for 82% of HCV Cases in the United States1
1. Smith BD, et al. Hepatology. 2011; 54(4):554A.2. 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.
$/QALY
Comparison of HCV Cost-Effectiveness With Other Routine Preventive Services
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
Breast CA,aged 40+
60,000
50,000
40,000
30,000
20,000
10,000
0
$/Q
AL
Y
Colorectal,aged 50+
Flu,aged 50+
Hypertension,aged 18+
HCV testing,1945-1965
HIV testing,aged 13-64
Cholesterolscreening
QALY= quality-adjusted life year.
› 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
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 ECHOExtension 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 Diabetes Child Psychiatry – Asthma Chronic Pain 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 Pain Management
Inflammatory Bowel Disease Rheumatoid Arthritis
Cognitive Dysfunction in the Aged Chronic Kidney Disease
Eating Disorders HIV Treatment
Solid Organ Transplant
Project ECHO
Primary Care Providers bringing value driven specialty care to patients and
communities through today’s technology