hepatitis c is it curable ?
TRANSCRIPT
Hepatitis C: Is it Curable?Hepatitis C: Is it Curable?
Dr. Noor A Abonewair, MRCP(UK)Dr. Noor A Abonewair, MRCP(UK)
Consultant Consultant Physician&GastroenterologistPhysician&Gastroenterologist
KFH, Taif, KSAKFH, Taif, KSA
May 2010May 2010
ObjectivesObjectives
• Discuss Hep C Infection & Current Discuss Hep C Infection & Current TreatmentTreatment
• Describe Hep C Treatment in CorrectionsDescribe Hep C Treatment in Corrections
• Explain New Medications for Hep CExplain New Medications for Hep C
• Outline Challenges Presented by New Outline Challenges Presented by New MedicationsMedications
• Propose Strategies to Address these Propose Strategies to Address these ChallengesChallenges
Hepatitis CHepatitis C• Hepatitis C (HCV) is a Hepatitis C (HCV) is a
flavivirus related to flavivirus related to Yellow Fever and Yellow Fever and West Nile VirusWest Nile Virus
• Most common Most common chronic bloodborne chronic bloodborne infection in the USinfection in the US
• Contagious liver Contagious liver disease causing mild disease causing mild illness to serious, illness to serious, lifelong illness or lifelong illness or deathdeath
Hep C TransmissionHep C Transmission
• Spread by blood to blood contact:Spread by blood to blood contact:– IV drug useIV drug use– Mother to child transmission (about 6%)Mother to child transmission (about 6%)– Can be sexually transmitted but less Can be sexually transmitted but less
commoncommon– Since 1992, screening has limited spread Since 1992, screening has limited spread
through transfusions and transplants through transfusions and transplants • For most, acute infection leads to For most, acute infection leads to
chronic infection chronic infection There is no vaccine for Hepatitis C. There is no vaccine for Hepatitis C. Concomitant HIV infection is thought to Concomitant HIV infection is thought to
increase the risk of transmission.increase the risk of transmission.
Hep C StatisticsHep C Statistics• 3.2 million persons chronically infected3.2 million persons chronically infected• 1.8% prevalence in the free world1.8% prevalence in the free world• Of every 100 people with Hep C Of every 100 people with Hep C
– 75–85 people will develop chronic Hepatitis 75–85 people will develop chronic Hepatitis C infectionC infection
– 60–70 people will go on to develop chronic 60–70 people will go on to develop chronic liver diseaseliver disease
– 5–20 people will go on to develop cirrhosis 5–20 people will go on to develop cirrhosis over 20–30 years over 20–30 years
– 1–5 people will die from cirrhosis or liver 1–5 people will die from cirrhosis or liver cancercancer
• 8000 to 10,000 deaths each year in US8000 to 10,000 deaths each year in US• Majority unaware of infection- not Majority unaware of infection- not
clinically illclinically ill Hepatitis C. Centers for Disease Control & Prevention, 2011.
Hepatitis C. Centers for Disease Control & Prevention, 2011.
Fibrosis & Disease Progression in Hepatitis C. Marcellin, et al. Hepatology, 2002
Hepatitis C ProgressionHepatitis C Progression
Hepatitis C ProgressionHepatitis C Progression• Mechanisms associated with progression of Mechanisms associated with progression of
fibrosis are poorly understood fibrosis are poorly understood • Rate of progression variable but slow in Rate of progression variable but slow in
generalgeneral• Older age, male gender, excessive alcohol Older age, male gender, excessive alcohol
consumption, overweight, and immune consumption, overweight, and immune deficiency associated with more rapid deficiency associated with more rapid progression progression
• Alcohol consumption controlled in correctional Alcohol consumption controlled in correctional environmentenvironment
• Treatment of overweight & HIV is criticalTreatment of overweight & HIV is critical
Fibrosis & Disease Progression in Hepatitis CFibrosis & Disease Progression in Hepatitis C. Marcellin, et al. Hepatology, 2002. Marcellin, et al. Hepatology, 2002
Hepatitis C TrendsHepatitis C Trends
• Most patients infected 20-40 years ago Most patients infected 20-40 years ago before virus identification and screeningbefore virus identification and screening
• Incidence decreasing but number of Incidence decreasing but number of patients developing cirrhosis, cancer & patients developing cirrhosis, cancer & end stage liver disease increasing (peak end stage liver disease increasing (peak 2020 to 2030)2020 to 2030)
• Total cost of care for untreated Hep C will Total cost of care for untreated Hep C will continue to increase over next 20 yearscontinue to increase over next 20 years
• Consensus on when and how Hep C will be Consensus on when and how Hep C will be treated in Corrections is needed nowtreated in Corrections is needed now
People are often asymptomatic after exposure to People are often asymptomatic after exposure to the virus, but about 20% will develop acute the virus, but about 20% will develop acute hepatitis; some of them will experience hepatitis; some of them will experience malaise, weakness and anorexia. malaise, weakness and anorexia.
Up to 85% of those exposed do not clear the virus Up to 85% of those exposed do not clear the virus and go on to develop CHC. Progression of the and go on to develop CHC. Progression of the disease occurs over 20–50 years.disease occurs over 20–50 years.
About 5–30% of people initially infected will About 5–30% of people initially infected will developdevelop
cirrhosis within 20 years and a small percentage cirrhosis within 20 years and a small percentage of these are at high risk of developing of these are at high risk of developing hepatocellular ca. hepatocellular ca.
One third may never progress to cirrhosis or will One third may never progress to cirrhosis or will not progress for at least 50 years. not progress for at least 50 years.
Some people with end-stage liver disease or Some people with end-stage liver disease or hepatocellular ca may require liver hepatocellular ca may require liver transplantation.transplantation.
Six major genetic types of HCV have been identified.Six major genetic types of HCV have been identified.
Genotype 1 (G1)Genotype 1 (G1) is the most common in the UK, and is the most common in the UK, and is found in about 40–50% of cases and in 24% in is found in about 40–50% of cases and in 24% in KSA. KSA.
Genotypes 2 and 3 (G2/3)Genotypes 2 and 3 (G2/3) contribute another 40– contribute another 40–50%, and 50%, and
Genotypes 4, 5 and 6Genotypes 4, 5 and 6 constitute the remainder of constitute the remainder of about 5%. about 5%.
Response to treatment varies between different Response to treatment varies between different genotypes. genotypes.
G1 is relatively more common among people G1 is relatively more common among people infected through blood products, and G2/3 is infected through blood products, and G2/3 is relatively more common among people who inject relatively more common among people who inject themselves with illicit drugs.themselves with illicit drugs.
G 4 is the commonest type in KSA (62%)G 4 is the commonest type in KSA (62%)
HCV: The FACTSHCV: The FACTS
• ~6 million Americans infected with HCV~6 million Americans infected with HCV– Fourfold increase in prevalence expected by Fourfold increase in prevalence expected by
20152015• Most common blood-borne infection in USMost common blood-borne infection in US• Aged 40-59 with greatest prevalenceAged 40-59 with greatest prevalence
– African-Americans 6.1%African-Americans 6.1%• Less than 150,000 people treatedLess than 150,000 people treated• Disease is curabl Disease is curabl • ~ 500,000 infected in KSA, 400,000 at ~ 500,000 infected in KSA, 400,000 at
risk of long-term liver diseaserisk of long-term liver disease• HCV seroprevalence in apparently HCV seroprevalence in apparently
healthy blood donors in KSA about 1.1 %.healthy blood donors in KSA about 1.1 %.
Introduction: Evolution of HCV Therapy Introduction: Evolution of HCV Therapy Unprecedented SuccessUnprecedented Success
40
60
20
80
IFN0
IFNHDD*
IFNRBV
PEG2b
PEG2a
PEG-2bRBV
PEG-2aRBV
% H
CV
-RN
A (
-)
Sustained responseEOT
1990s 2008 . . . *HDD = high dose and longer duration
Current Hepatitis C Current Hepatitis C TreatmentTreatment• PEG-InterferonPEG-Interferon
– Increases expression of proteins that Increases expression of proteins that interfere with Hep C viral replicationinterfere with Hep C viral replication
• RibavirinRibavirin– Enhances the antiviral effect of interferonEnhances the antiviral effect of interferon– Precise mechanism of action uncertainPrecise mechanism of action uncertain
• Treatment lasts for one year; if Treatment lasts for one year; if successful, induces curesuccessful, induces cure
Hepatitis Treatment and Management. Mukherjee, et al. Medscape Reference, 2011
What does curable mean?What does curable mean?
• Sustained viral response (SVR)Sustained viral response (SVR)
• HCV-RNA negative in serumHCV-RNA negative in serum
• HCV-RNA negative in liverHCV-RNA negative in liver
What is a SVR?What is a SVR?
• HCV-RNA undetectable 24 weeks after HCV-RNA undetectable 24 weeks after stopping therapystopping therapy
• Type of therapy not importantType of therapy not important– InterferonInterferon– Interferon + ribavirinInterferon + ribavirin– Newer therapiesNewer therapies– In order to use the word “cure”, this response In order to use the word “cure”, this response
must be durablemust be durable
Criteria for achieving a SVRCriteria for achieving a SVR
• The ability to achieve a SVR is the result of The ability to achieve a SVR is the result of 3 independent steps3 independent steps– The patient must achieve a virologic responseThe patient must achieve a virologic response– The patient must maintain the responseThe patient must maintain the response– The patient must not relapseThe patient must not relapse
• SVR = virologic response - (breakthrough SVR = virologic response - (breakthrough + relapse)+ relapse)
• To overcome To overcome non-responsenon-response and relapse, and relapse, the reasons for failure must be definedthe reasons for failure must be defined
Current SVR Rates with Peg-IFN plus Current SVR Rates with Peg-IFN plus RBVRBV
Genotype Non-1Genotype Non-1Genotype 1Genotype 1
Strader DB et al. Strader DB et al. Hepatology.Hepatology. 2004;39:1147-1171. 2004;39:1147-1171.
42%-46%42%-46%42%-46%42%-46%
76%-82%76%-82%76%-82%76%-82%
48 weeks
24 weeks
Factors Predicting a Response to Factors Predicting a Response to TherapyTherapy
Fixed Variable GenotypeGenotype
Viral load Viral load
Liver histology Liver histology
Rapidity of Rapidity of viral clearanceviral clearance
ALT levelALT level
Duration of infectionDuration of infection
AgeAge
SexSex
RaceRace
Type of therapyType of therapy
– Dose and durationDose and duration
Adherence to therapyAdherence to therapy
Patient SizePatient Size
Hepatic steatosisHepatic steatosis
0
20
40
60
80
100
SV
R (
%)
87%
52%
n=120 n=82
RVR is a strong predictor of RVR is a strong predictor of achieving SVRachieving SVR
Ferenci P, et al. J Hepatol 2005: 43: 425RVR = HCV RNA <50 IU/mL at week 4
PEGASYS 180 g/wk + COPEGUS 1000/1200 mg/day; all genotypes
HCV RNA <50 IU/mL at
week 4
HCV RNA >50IU/ml at
week 4
10
30
50
70
90
Definitions of virological response at week Definitions of virological response at week 4 and week 124 and week 12
HC
V R
NA
dec
reas
e (I
U/m
L)
EOTR SVR
724 48Weeks of therapy
0 12
Undetectable HCV RNA (<50 IU/mL)
0 RVR = undetectable HCV RNA at week 4
cEVR = no RVR but undetectable HCV RNA at week 12
>2 log10
pEVR = no RVR and detectable HCV RNA, but >2 log10 drop at week 12
24
RVR = rapid virological response; cEVR = complete early virological response; pEVR = partial early virological response.
Why aren’t we treating Why aren’t we treating patients?patients?
Real World Experience Showed Limited Real World Experience Showed Limited Impact of Current HCV TreatmentsImpact of Current HCV Treatments
6%
12%
13%
18%
51%
0% 10% 20% 30% 40% 50% 60%
Lost to follow-up
Relapse
SVR
Stopped treatment (side effects)
Nonresponse
5%
11%
13%
34%
37%
0% 10% 20% 30% 40%
Normal ALT
Patient Choice
Alocohol or drug Abuse
Contraindications
Nonadherence
Treated28%
Untreated72%
Yngve Falck-Ytter, MD et al. Annals of Internal Medicine 2002:136:288-292
Based on a retrospective case series of consecutively referred patients at a teaching county hospital in Cleveland, Ohio
n=293
How can we improve cure How can we improve cure rates?rates?
• Make current therapy easier take Make current therapy easier take
• Extend duration of therapyExtend duration of therapy
• Increase dosagesIncrease dosages
• New therapiesNew therapies
• Place more importance of viral kineticsPlace more importance of viral kinetics
• Realize that not one size fits allRealize that not one size fits all
“Tailored” Treatment in Genotype I
Genotype 1 patients with an RVR Genotype 1 patients with an RVR can be treated for 24 weekscan be treated for 24 weeks
0
20
40
60
SV
R (
%)
80
100
PEGASYS 180 g/wk plus COPEGUS 1000/1200 mg/day
88% 91%
1. Jensen D, et al. Hepatology 2006; 43: 9542. Ferenci P, et al. 41st EASL 2006; Abstract 8
G1 = genotype 1RVR = HCV RNA <50 IU/mL at week 4
10
30
50
70
90 84%
24 weeks
Ferenci et al.2
n= 33 56 68
24 weeks 48 weeks
Jensen et al.1
Very high SVR rates with 24 weeks’ Very high SVR rates with 24 weeks’ therapy in genotype 1 patients with an therapy in genotype 1 patients with an RVR and LVLRVR and LVL
0
20
40
60
SV
R (
%)
80
100
24 weeks 48 weeks
93% 96%
n= 27 27
PEGASYS EU SPC, revised 2007(based on: Jensen D, et al. Hepatology 2006; 43: 954)
RVR = HCV RNA <50 IU/mL at week 4LVL (low viral load) ≤800 000 IU/mL; HVL (high viral load) >800 000 IU/mL
10
30
50
70
90 Very few patients with HVL achieve RVR. Of these, 88% achieve SVR with 48 weeks’ PEGASYS + COPEGUS (SD)
PEGASYS 180 g/wk plus COPEGUS 1000/1200 mg/day
High rates of SVR in genotype 4 High rates of SVR in genotype 4 patients with an RVRpatients with an RVR
n= 50 69
86%
58%
Kamal S, et al. Hepatology 2007; Epub ahead of print
Pegylated interferon alfa-2b (12KD) 1.5 g/kg/wk + RBV 10.6 mg/kg/day
Overall48 weeks
SV
R (
%)
0
20
40
60
80
100
RVR24 weeks
RVR = HCV RNA <50 IU/mL at week 4
10
30
50
70
90
Optimising outcomes in genotype 1/4Optimising outcomes in genotype 1/4
• Patients with a LVL who achieve an RVR Patients with a LVL who achieve an RVR may be candidates for shorter treatment may be candidates for shorter treatment durationduration
• Patients with a cEVR achieve high SVR Patients with a cEVR achieve high SVR rates with 48 weeksrates with 48 weeks’’ therapy therapy
• Slow responders who do not achieve Slow responders who do not achieve HCV RNA negativity by week 4 or 12 may HCV RNA negativity by week 4 or 12 may be candidates for treatment be candidates for treatment intensification (longer duration, higher intensification (longer duration, higher doses)doses)
Extending treatment durationExtending treatment duration
• Three studies have investigated 72 Three studies have investigated 72 weeksweeks’’ treatment duration with PEGASYS treatment duration with PEGASYS plus COPEGUSplus COPEGUS11––33
– Two of these studies used low-dose COPEGUS Two of these studies used low-dose COPEGUS 800 mg/day 800 mg/day1,21,2
– One study used standard-dose COPEGUS One study used standard-dose COPEGUS 1000/1200 mg/day1000/1200 mg/day33
1. Sánchez-Tapias J, et al. Gastroenterology 2006; 131: 4512. Berg T, et al. Gastroenterology 2006; 130: 1086
3. Ferenci P, et al. 57th AASLD 2006; Abstract 390
Ferenci et al.G1/4RBV 1000/1200 mg
Study designs: summaryStudy designs: summary
48 weeks72 weeks
48 weeks72 weeks
48 weeks72 weeks
RVR
RVR
NR
12Week
Berg et al.G1 onlyRBV 800 mg
Sánchez-Tapias et al.All genotypesRBV 800 mg
Randomisation
48 724 0
1. Berg T, et al. Gastroenterology 2006; 130: 1086 2. Sánchez-Tapias J, et al. Gastroenterology 2006; 131: 451
3. Ferenci P, et al. 57th AASLD 2006; Abstract 390
Proportion of patients with complete Proportion of patients with complete or partial EVRor partial EVR
StudyStudy complete EVRcomplete EVR partial EVRpartial EVR
Berg et al.Berg et al.11 166/455 166/455 (36(36%)%) 92/455 (20%)92/455 (20%)
TeraVic-4TeraVic-422 132/326 132/326 (40(40%)%) 56/326 (1756/326 (17%)%)
Ferenci et al.Ferenci et al.** 106/184 106/184 (58%)(58%) 41/184 (2241/184 (22%)%)
complete EVR = no RVR but HCV RNA <50 IU/mL at week 12partial EVR = no RVR and >2 log10 drop but HCV RNA >50 IU/mL at week 12* Includes small number (<10%) of G4 patients
Sánchez-Tapias JM, et al. APASL 2007; Abstract 0-196
No consistent improvement with 72 No consistent improvement with 72 weeks’ therapy in G1 patients with a weeks’ therapy in G1 patients with a complete EVRcomplete EVR
Complete EVR = no RVR but HCV RNA <50 IU/mL at week 12* Includes small number (<10%) of G4 patients
78%
87%
Ferenci et al.* RBV 1000/1200 mg/day
77%70%
Berg et al. RBV 800 mg/day
SV
R (
%)
52%61%
0
10
20
30
40
50
60
70
80
90
100
n= 79 87 58 74 60 46
TeraVic-4 RBV 800 mg/day
48 weeks72 weeks
Sánchez-Tapias JM, et al. APASL 2007; Abstract 0-196
Consistent improvement with 72 Consistent improvement with 72 weeks’ therapy in G1 patients with a weeks’ therapy in G1 patients with a partial EVRpartial EVR
partial EVR = no RVR and >2 log10 drop but HCV RNA >50 IU/mL at week 12* Includes small number (<10%) of G4 patients
SV
R (
%)
16%
44%
0
10
20
30
40
50
60
70
80
90
100
n= 46 46 31 25 25 16
TeraVic-4 RBV 800 mg/day
33%
46%
Berg et al. RBV 800 mg/day
52%
69%
Ferenci et al.* RBV 1000/1200 mg/day
48 weeks72 weeks
Sánchez-Tapias JM, et al. APASL 2007; Abstract 0-196
Extending treatment duration: Extending treatment duration: summarysummary
• Genotype 1 patients with a partial EVR Genotype 1 patients with a partial EVR (no RVR and detectable HCV RNA but >2 (no RVR and detectable HCV RNA but >2 loglog1010 drop at week 12) gain considerable drop at week 12) gain considerable benefit from extension of therapy from 48 benefit from extension of therapy from 48 to 72 weeksto 72 weeks
• The proportion of genotype 1 patients The proportion of genotype 1 patients that benefit from extended therapy is that benefit from extended therapy is small but significantsmall but significant
• These results need to be confirmed in These results need to be confirmed in randomised trialsrandomised trials
Possible Treatment Algorithm Possible Treatment Algorithm Viral Kinetics in Genotype 1Viral Kinetics in Genotype 1
Week 4Week 4
RVRRVRWk 12Wk 12
HCV RNAHCV RNASignificantSignificant
AEsAEsDuration of Duration of
TherapyTherapy
YESYES UndetectablUndetectablee
NoNo 48 wk48 wk
NONO UndetectablUndetectablee
NoNo 48 wk48 wk
YESYES UndetectablUndetectablee
YesYes Consider d/c Consider d/c at 24 wkat 24 wk
NONO Present*Present* NoNo Consider Consider
72 wk72 wkDavis GL. Davis GL. HepatologyHepatology. 2006;43:909. 2006;43:909*Patient subsequently becomes HCV RNA negative between wk 12 and wk 24
““Tailored” Treatment in Tailored” Treatment in Genotypes 2 and 3Genotypes 2 and 3
RVR is a strong predictor RVR is a strong predictor of SVR in genotype 2/3of SVR in genotype 2/3
PEGASYS 180 g/wk plus COPEGUS 800 mg/day for 24 weeks
SVR: 90% (370/410)
RVR, HVL: 42%
No RVR: 34%
RVR, LVL:24%
SVR: 49% (105/215) SVR: 94%
(141/150)
SVR: 88% (229/260)
Data from ACCELERATE. Roche data on file
<50 IU/mL at week 4 (RVR) and LVL (≤800 000 IU/mL)
<50 IU/mL at week 4 (RVR) and HVL (>800 000 IU/mL)
>50 IU/mL at week 4 (No RVR)
HCV RNA response:
ACCELERATE Study DesignACCELERATE Study DesignGenotypes 2 and 3Genotypes 2 and 3
Ra
nd
om
ize Follow-up
Follow-up
Shiffman et al. NEJM 2007
Peg-IFN α-2a (180 g/wk)
+ RBV (800 mg/d)
Peg-IFN α-2a (180 g/wk) + RBV (800 mg/d)
Randomized (1:1), open-label study; 132 centers; n = 1469; HCV 2/3
Weeks0 16 24 40 48
ACCELERATE: 24 weeks is more ACCELERATE: 24 weeks is more effective than 16 weeks in genotype effective than 16 weeks in genotype 2/3 patients2/3 patients
Standard analysis
SV
R (
%)
n=679 n=630
65%
76%
0
20
40
60
80
100
10
30
50
70
90
16 weeks 24 weeks
PEGASYS 180 g/wk plus COPEGUS 800 mg/day
Shiffman M, et al. N Engl J Med 2007; 357: 124
ACCELERATE StudyACCELERATE StudyImpact of RVRImpact of RVR
8084
26 28
91 89
58
43
0
100
HCV-2 HCV-3 HCV-2 HCV-3
SV
R (
%)
Peg-IFN -2a + RBV16 wk24 wk
n = 244 213 217 197 96 86 109 129
Patients With an RVR Patients Without an RVR
Overall 24 vs 16 weeksRVR +: 90 vs 82%, P = 0.0007RVR -: 49 vs 27%, P <0.001Shiffman et al. NEJM 2007
Very high SVR rates with shorter Very high SVR rates with shorter duration in G2/3 patients with an RVR duration in G2/3 patients with an RVR and LVLand LVL
16 weeks PEGASYS plus COPEGUS24 weeks PEGASYS plus COPEGUS
n=123 n=101 n=295 n=260 n=49n=43
≤400 000 IU/mL 400–800 000 IU/mL >800 000 IU/mL
90%84%
78%
95%92% 88%
SV
R (
%)
0
20
40
60
80
100
Standard analysis Shiffman M, et al. 57th AASLD 2006; Abstract 340
Optimising outcomes in genotype 2/3: Optimising outcomes in genotype 2/3: conclusionconclusion
• Patients with an RVR achieve high SVR Patients with an RVR achieve high SVR rates >90% rates >90% with a shorter durationwith a shorter duration
• Patients without an RVR achieved an SVR Patients without an RVR achieved an SVR of 49% with 24 weeksof 49% with 24 weeks
• The possibility of improving SVR in non-The possibility of improving SVR in non-RVR patients by intensifying treatment RVR patients by intensifying treatment (longer duration/higher RBV doses) will be (longer duration/higher RBV doses) will be explored in a prospective trial (NCORE explored in a prospective trial (NCORE 2/3 study; N=400)2/3 study; N=400)
How can we improve current How can we improve current responceresponce??
• Not one size fits all use of current Not one size fits all use of current therapiestherapies
• Newer interferons (Albinterferon)Newer interferons (Albinterferon)
• New therapiesNew therapies– Protease inhibitors (Telaprevir)Protease inhibitors (Telaprevir)– Polymerase inhibitorsPolymerase inhibitors– Nitazoxanide (unknown mechanism, Nitazoxanide (unknown mechanism,
antiviral, antiparasitic, now in phase II in antiviral, antiparasitic, now in phase II in G4 in Egypt)G4 in Egypt)
New Hepatitis C TreatmentNew Hepatitis C Treatment
• FDA recently approved two new protease FDA recently approved two new protease inhibitors for treatment of Hep Cinhibitors for treatment of Hep C– BoceprevirBoceprevir– TelaprevirTelaprevir
• Are added to, do not replace, original therapyAre added to, do not replace, original therapy• Indications: Indications:
– treatment of chronic Hep C genotype 1 treatment of chronic Hep C genotype 1 – with compensated liver disease, including with compensated liver disease, including
cirrhosiscirrhosis– previously untreated or who have failed previous previously untreated or who have failed previous
interferon and ribavirin therapy.interferon and ribavirin therapy.
New Hepatitis C TreatmentNew Hepatitis C Treatment
• In previously untreated patients, 79% of In previously untreated patients, 79% of those receiving telaprevir experienced a those receiving telaprevir experienced a sustained virologic response (SVR) sustained virologic response (SVR) compared with less than 50% with compared with less than 50% with peginterferon alfa and ribavirin treatment peginterferon alfa and ribavirin treatment alone. alone.
• Cure rate for patients treated with telaprevir Cure rate for patients treated with telaprevir across all studies, and across all patient across all studies, and across all patient groups, was between 20-45% higher than groups, was between 20-45% higher than current regimen.current regimen.
• Course of treatment decreased from 48 Course of treatment decreased from 48 weeks to 24 weeks.weeks to 24 weeks.
US Food and Drug Administration (FDA). FDA approves Incivek for hepatitis C. May 23, 2011.
Challenges of New Challenges of New TreatmentTreatment• Cannot be given alone or resistance will Cannot be given alone or resistance will
developdevelop• Same side effects plus additional side effectsSame side effects plus additional side effects
– AnemiaAnemia– NeutropeniaNeutropenia– ThrombocytopeniaThrombocytopenia– Severe RashSevere Rash
• Logistical Challenges in the correctional Logistical Challenges in the correctional environment:environment:– Must be given at same time every dayMust be given at same time every day– Must be given with fatty food (e.g., ice cream)Must be given with fatty food (e.g., ice cream)
Cost of New TreatmentCost of New Treatment• Both boceprevir and telaprevir are Both boceprevir and telaprevir are
priced for curepriced for cure
• $45,000 to $75,000 per patient$45,000 to $75,000 per patient
• Prevalence of Hep C higher in Prevalence of Hep C higher in correctional patient populationcorrectional patient population
• In Delaware, 800/7000 patients with In Delaware, 800/7000 patients with Hep CHep C
• Treatment of entire population with new Treatment of entire population with new regimen would cost up to $60,000,000. regimen would cost up to $60,000,000.
• Entire healthcare budget = Entire healthcare budget = $55,000,000.$55,000,000.
Strategies for Hep C Strategies for Hep C TreatmentTreatment• The Federal Bureau of Prisons uses the The Federal Bureau of Prisons uses the
following criteria for limiting Hep C following criteria for limiting Hep C treatmenttreatment– PEG-interferon contraindicatedPEG-interferon contraindicated– Incarceration period insufficient for Incarceration period insufficient for
treatmenttreatment– Inmate has unstable medical or mental Inmate has unstable medical or mental
health conditionhealth condition– Patient refuses treatmentPatient refuses treatment
Strategies for Hep C Strategies for Hep C TreatmentTreatment• Monitoring early stages of Hep C rather Monitoring early stages of Hep C rather
than treatment acceptable and occurs in than treatment acceptable and occurs in free worldfree world
• Treatment based on progression:Treatment based on progression:– Liver function testsLiver function tests– Liver biopsyLiver biopsy– Other factors: age, co-infection with HIV, etc.Other factors: age, co-infection with HIV, etc.
• Monitor patients with earlier stages of Monitor patients with earlier stages of fibrosis & sentences under 5 years & fibrosis & sentences under 5 years & coordinate with community providers for coordinate with community providers for potential treatment potential treatment
Consensus on Use of New Consensus on Use of New MedicationsMedications
• If fibrosis progression indicates treatment, If fibrosis progression indicates treatment, patients are tried on current therapy firstpatients are tried on current therapy first
• If therapy found to be futile at 12 weeks, If therapy found to be futile at 12 weeks, patients are tried on new medical regimen, patients are tried on new medical regimen, provided there are no contraindicationsprovided there are no contraindications
• As with current practice, patients should be As with current practice, patients should be involved in the decision to treat whether involved in the decision to treat whether using old or new regimenusing old or new regimen
CONCLLSIONCONCLLSION
Hepatitis C: Is it curable?Hepatitis C: Is it curable?
• Current published data supports the Current published data supports the opinion that it is curableopinion that it is curable
• Small amounts of virus may remain Small amounts of virus may remain in the liver after SVRin the liver after SVR– They also may be present in a normal They also may be present in a normal
populationpopulation
• Current therapies are effective and Current therapies are effective and improving improving
Hepatitis C: Is it curable?Hepatitis C: Is it curable?
• Disseminating this information to the Disseminating this information to the community of patients and health community of patients and health care providers at all levels may care providers at all levels may increase treatment ratesincrease treatment rates
• Very important message to take Very important message to take home is YES Hepatitis C is curablehome is YES Hepatitis C is curable
