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HCV Infection: Magnitude of the Problem

CDC. MMWR Morb Mortal Wkly Rep. 1998;47;1-39. NIH Consensus Conference Statement. Available at: http://consensus.nih.gov/2002/ 2002HepatitisC2002116html.htm. Accessed August 19, 2008. Rustgi VK. J Gastroenterol. 2007;42:513-521.

Approximately 3.9 million persons in United States infected

– Approximately 35,000 new cases yearly

– 85% of new cases become chronic

10,000-20,000 HCV-related deaths per year

– Number expected to triple in next 10-20 years

Leading cause of

– Chronic liver disease

– Cirrhosis

– Liver cancer

– Liver transplantation



Lindsay KL. Hepatology. 2002;36(suppl 1):S114-S120.

Goals of HCV Therapy

Primary goal of treatment is to eradicate the virus

Additional goals

– Slow disease progression

– Minimize risk of HCC

– Improve liver histology

– Enhance quality of life

– Prevent transmission of virus

– Reduce extrahepatic manifestations



SVR Rates With Standard IFN

McHutchison J, et al. N Engl J Med. 1998;339:1485-1492. Poynard T, et al. Lancet. 1998;352: 1426-1432.

100

80

60

40

20

0

19

43

6

IFN24 Weeks

IFN48 Weeks

IFN/RBV48 Weeks

SV

R (

%)



Overall GT 1 GT 2/3

SVR With PegIFN: > 50% of GT 1 Patients Do Not Respond PegIFN alfa-2b 1.5 µg/kg/week +

RBV 800 mg/day for 48 weeks[1]

PegIFN alfa-2a 180 µg/week + weight-based RBV (1000 or 1200 mg/day) for 48 weeks[2]

1. Manns M, et al. Lancet. 2001;358:958-965. 2. Fried MW, et al. N Engl J Med. 2002;347:975-982.

42

82

100

80

60

40

20

0

54

SV

R (

%)

n = 348 n = 163n = 511

46

76

56

Overall GT 1 GT 2/3n = 298 n = 140n = 453

Patterns and Predictors of Response



PegIFN/RBV

SVRRVR cEVR

Virologic Responses

Slow virologic response

0

1

2

3

4

5

6

7

8

EVR 2 log10 decline

Limit of detection

Weeks

0 4 12 18 24 30 36 42 48 54 60 66 728 78

HC

V R

NA

(lo

g10

IU

/mL

)



Null response

Suboptimal Virologic Responses

Relapse

Breakthrough

PegIFN/RBV

Partial response 2 log10 decline

Limit of detection

Weeks

0 4 12 18 24 30 36 42 48 54 60 66 728 78

HC

V R

NA

(lo

g10

IU

/mL

)

0

1

2

3

4

5

6

7

8



HCV Treatment: Key Predictors of Response

1995-2000 Current

GT 2 or 3 Absence of fibrosis Low HCV RNA Younger age Female sex Weight

GT 2 or 3 Lack of steatosis Adherence Early response RBV dosage Race

Manns MP, et al. Lancet. 2001;358:958-965. Fried MW, et al. N Engl J Med. 2002;347:975-982. Muir AJ, et al. N Engl J Med. 2004;350:2265-2271. Conjeevaram HS, et al. Gastroenterology. 2006;131:470-477.



Key Principles Regarding Nonresponse Inadequate dosing/treatment

– Patient factors may require higher treatment dosages

Compliance

– Adverse effects can require dose reductions or interruptions

– May be able to maintain treatment through better management of adverse effects

Steatosis

– Insulin resistance can impair response to HCV therapy

– Differences in mechanisms, management according to HCV genotype

Some patients may be inherently resistant to IFN

Preventing Relapse



Key Principles Regarding Relapse

Viral kinetics

– Importance of duration of HCV RNA negativity

– Slow responders may not be treated for adequate duration

– Key for GT 1 patients

RBV dosage

– Inadequate dosage of RBV associated with higher rates of relapse



Retrospective analysis of GT 1 patients receiving 48 weeks of pegIFN alfa-2a + RBV (N = 453)

Longer Duration of Undetectability on Treatment Increases Chance for SVR

HCV RNA Positive

at Week 24

4 12 24Week Became HCV RNA Negative

91

66

45

2

Ferenci P, et al. J Hepatol. 2005;43:425-433.

20

40

60

80

100

SV

R (

%)

0



GT 1 Patients Without RVR Benefit From Longer Therapy

Treatment-Naive Patients Received PegIFN alfa-2a 180 µg/week + RBV 800 mg/day

Sanchez-Tapias JM, et al. Gastroenterology. 2006;131:451-460.

32

45

28

44

All Patients Without RVR GT 1, No RVR

SV

R (

%)

20

40

60

80

100

P = .01 P = .003

149 142165 1610

48 weeks72 weeks

n =



Berg T, et al. Gastroenterology. 2006;130:1086-1097.

Longer Therapy in GT 1 Pts Without cEVR but Week 24 Negative HCV RNA

Pat

ien

ts (

%)

Post Hoc Analysis of Slow Responders Who Completed PegIFN alfa-2a 180 µg/week + RBV 800 mg/day and Follow-up

17

29

64

40

48 weeks (n = 147)72 weeks (n =158)

SVR Relapse

30/47 21/5217/100 31/106

P = .04

P = .02

20

40

60

80

100

0



Dusheiko G, et al. Antivir Ther. 2008;13(suppl 1):23-30.

Ribavirin Is Critical to the Success of HCV Combination Therapy Role of RBV in successful antiviral therapy

– Antiviral activity

– Prevention of relapse

Can we optimize treatment by fine tuning the use of RBV?

– How important is the initial dose of RBV?

– Do we need to maintain the RBV dose for the duration of treatment?



Increase in SVR by Prevention of Relapse With Addition of RBV 48 weeks of treatment with pegIFN alfa-2a ± RBV

SVR RelapseETR

Pat

ien

ts (

%)

56

29

0

20

40

60

80

100

n = 224 453 224 453 132 313

PegIFN alfa-2a 180 µg/week +RBV 1000/1200 mg/day

PegIFN alfa-2a 180 µg/week

51*

19

69

59

P = .01

P < .001

*P value not specified.Fried MW, et al. NEJM. 2002; 347:975-982.



Increased SVR Rate With Higher RBV Starting Dose in Clinical Trials

41

N = 250 271

52

RBV 800 mg/day RBV 1000/1200 mg/day

Hadziyannis S, et al. Ann Intern Med. 2004;140:346-355.

SV

R (

%)

0

20

40

60

80

100

GT 1 patients treated with pegIFN alfa-2a 180 µg/week + RBV for 48 weeks



GT 1 patients treated with pegIFN alfa-2a 180 µg/week + RBV 1000/1200 mg/day

Dose-Dependent Increase in SVR With RBV Dosage > 10 mg/kg/day

Snoeck E, et al. Br J Clin Pharmacol. 2006;62: 699-709.

RBV Dose/Body Weight (mg/kg) Probability of Achieving SVR

5 ~ 0.38

10 ~ 0.38

15 ~0.52

20 ~ 0.75



All patients treated with pegIFN alfa-2a 180 µg/week + RBV 1000/1200 mg/day

Dose-Dependent Increase in Anemia With RBV Dose > 15 mg/kg/day

Snoeck E, et al. Br J Clin Pharmacol 2006; 62: 699-709.

RBV Dose/Body Weight (mg/kg) Incidence of Hemoglobin < 10 g/dL

5 ~ 0.08

10 ~ 0.08

15 ~0.18

17.5 ~ 0.25

20 ~ 0.41



RBV Exposure and SVR: GT 1 and Treatment Completers

Reddy KR, et al. Clin Gastroenterol Hepatol. 2007;5:124-129.

Retrospective analysis of pegIFN alfa-2a/RBV phase III trials

6762

57

33

1922

32

54

0

20

40

60

80

> 97 > 80-97> 60-800-60

100

Pat

ien

ts (

%)

Cumulative RBV Exposure

SVR (P = .006) Relapse



RBV Exposure Weeks 13-48 After Full Exposure During Weeks 1-12

Reddy KR, et al. Clin Gastroenterol Hepatol. 2007;5:124-129.

Retrospective analysis of pegIFN alfa-2a/RBV phase III trials

> 97 > 80-97> 60-800-60

Pat

ien

ts (

%)

Cumulative RBV Exposure

36

52

69 67

8287

83 81

End-of-treatment response SVR (P = .0107)

0

20

40

60

80

100



Steatosis in HCV

1. Younossi ZM, et al. J Clin Gastroenterol. 2004;38:705-709. 2. Asselah T, et al. Gut. 2006;55:123-130. 3. Browning JD, et al. Hepatology. 2004;40:1387-95. 4. Nomura H, et al. Jpn J Med. 1988;27:142-149.

No steatosis (41%)

Steatosis (41%)

NASH (18%)

Steatosis a common comorbidity of HCV

– Found in 50% to 60% of HCV-infected patients[1,2] vs 14% to 30% in general population[3,4]

Proportion of Patients With Fatty Liver Disease Among 121 HCV-Infected Individuals With Available Liver Biopsies[1]



Metabolic Syndrome in HCV

Having at least 3 of the following conditions

– Abdominal circumference > 40" for men or > 35" for women

– Elevated triglycerides (≥ 150 mg/dL)

– Low levels of high density lipoprotein (< 40 mg/dL in men and < 50 mg/dL in women)

– Hypertension (blood pressure ≥ 130 mm Hg systolic or≥ 85 mm Hg diastolic)

– Hyperglycemia (fasting glucose ≥ 100 mg/dL)

Torpy JM, et al. JAMA. 2006;295:850.



2 Types of Steatosis in Hepatitis C

GT 3

Alcohol

Metabolic steatosis Insulin resistance

Viral steatosis (viremia)

HCV

Rubbia-Brandt L, et al. J Hepatol. 2000;33:106-115. Adinolfi LE, et al. Hepatology. 2001;33:1358-1364. Serfaty L, et al. Am J Gastroenterol. 2002;97:1807-1812. Monto A, et al. Hepatology. 2002;36:729-736. Poynard T, et al. Hepatology. 2003;38:75-85.

Steatosis

Overweight

Diabetes



Calculation of Insulin Resistance

HOMA

– Convert glucose in mg/dL to mmol/L, divide glucose by 18

– Values > 1.8-2.0 are consistent with insulin resistance

QUICKI

– Fasting insulin (µU/L) fasting glucose (mg/dL)

– Take log, then 1/

– Values < 0.35 are consistent with insulin resistance

Rough estimate: multiply fasting insulin glucose: values > 700 are typically consistent with insulin resistance

Fasting insulin (µU/L) fasting glucose (mmol/L)

22.5



462 HCV nondiabetic patients: HOMA-IR > 3 in 35%

*Age, sex, BMI, inflammation and fibrosis matched.

5

35

HO

MA

-IR

> 3

(%

)

P < .001

0

10

20

30

40

HBV (n = 80)*HCV (n = 240)

Insulin Resistance Common in Nondiabetic HCV Patients

Moucari R, et al. Gastroenterology. 2008;134:416-423.



Insulin Resistance and SVR in HCV GT 1 Patients

33

61

0

20

40

60

80

100

SV

R (

%)

With Insulin Resistance Without Insulin Resistance

Romero-Gomez M, et al. Gastroenterology. 2005;128:636-641.

P = .007



Response: 17.6%

Effect of Weight Loss on Antiviral Response

32 treatment-naive GT 1HCV patients with

metabolic syndrome

15 patients on low-calorie diet:

10% ↓ in BMI17 control patients

Response: 60.0%

pegIFN alfa-2b + RBV

HOMA: 4.86-3.45

(P = .0018)

Tarantino G, et al. Gut. 2006;55:585.

Retreatment Options for Patients With Previous

Treatment Failure



PegIFN + RBV in Previous Standard IFN Nonresponders

NR: IFN + RBV

10-15

SV

R (

%)

Previous HCV RNA reduction predicts

response;high relapse rate

(> 50%) in responders

0

20

40

60

80

100

Jacobson IM, et al. Am J Gastroenterol. 2005;100:2453-2462. Lawitz E, et al. DDW 2003. Abstract 9. Shiffman ML, et al. Gastroenterology. 2004;126:1015-1023. Gross J,

et al. Hepatology. 2005;42:220A. Krawitt EL, et al. J Hepatol. 2005;43:243-249.

Relapse: IFN + RBV

40-50

NR: IFN

25-30



Outcomes in Nonresponders to IFN-Based TherapyStudy Treatment GT N (Previous

Treatment)SVR Rate

(Previous Treatment)

Jacobson[1] PegIFN alfa-2b+ RBV x 48 weeks

1 (89%)2/3 (9%)

47 (IFN)219 (IFN/RBV)

21% (IFN)8% (IFN/RBV)

Sherman[2] PegIFN alfa-2a+ RBV x 48 weeks

1 36 (IFN)148 (IFN/RBV)


2/3 9 (IFN)19 (IFN/RBV)


RENEW[3] PegIFN alfa-2b 1.5 or 3.0 µg/kg/week + RBV

1 (91%) 704 (IFN/RBV) 12% 17%

HALT-C[4] PegIFN alfa-2a + RBV x 48 weeks

All 604 18%

EPIC3[5] PegIFN alfa-2b+ RBV x 48 weeks

1 (81%)2/3 (15%)

903 18%

1. Jacobson IM, et al. Am J Gastroenterol. 2005;100:2453-2462. 2. Sherman M, et al. Gut. 2006;55:1631-1638. 3. Gross J, et al. AASLD 2005. Abstract 60. 4. Shiffman ML, et al. Gastroenterology. 2004;126:1015-1023. 5. Poynard T, et al. EASL 2008. Abstract 988.



Outcomes in Nonresponders to PegIFN/RBVStudy Treatment GT N (Previous Treatment) SVR Rate


REPEAT[1] PegIFN alfa-2a + RBV x 48 weeks

1 (> 90%) 473 8%

PegIFN alfa-2a + RBV x 72 weeks

1 (> 90%) 469 16%

DIRECT[2] CIFN 9 µg/day + RBV

1 (95%) 245 5.3% at Week 12

CIFN 15 µg/day + RBV

1 (96%) 242 9.5% at Week 12

Nelson[3] AlbIFN + RBV 1 (> 90%) 115 (63% to 91% of patients previously

received pegIFN/RBV)

11% (GT 1 patients previously treated with

pegIFN/RBV)

EPIC3[4] PegIFN alfa-2b + RBV x 48 weeks

1 (81%)2/3 (15%)

196 (PegIFN alfa-2a)280 (PegIFN alfa-2b)

6% (PegIFN alfa-2a)7% (PegIFN alfa-2b)

1. Jensen DM, et al. AASLD 2007. Abstract LB4. 2. Bacon B, et al. AASLD 2007. Abstract 168. 3. Nelson DR, et al. AASLD 2007. Abstract 51. 4. Poynard T, et al. EASL 2008. Abstract 988.



Outcomes in Relapsers to IFN-Based TherapyStudy Treatment GT N (Previous

Treatment)SVR Rate


Jacobsonl[1] PegIFN alfa-2b+ RBV x 48 weeks

1 (89%)2/3 (9%)

55 (IFN/RBV) 42%

Sherman[2] PegIFN alfa-2a+ RBV x 48 weeks

1 15 (IFN)54 (IFN/RBV)


2/3 8 (IFN)23 (IFN/RBV)



1 (81%)2/3 (15%)

300 43%

1. Jacobson IM, et al. Am J Gastroenterol. 2005;100:2453-2462. 2. Sherman M, et al. Gut. 2006;55:1631-1638. 3. Gross J, et al. AASLD 2005. Abstract 60.



Study Treatment GT N (Previous Treatment)

SVR Rate(Previous Treatment)

Kaiser[1] CIFN 9 µg/day+ RBV x 72 weeks

1 120 69%

PegIFN alfa-2a+ RBV x 72 weeks

42%


1 (81%)2/3 (15%)

164 (PegIFN alfa-2a)180 (PegIFN alfa-2b)

34% (PegIFN alfa-2a)32% (PegIFN alfa-2b)

Outcomes in Relapsers to PegIFN-Based Therapy

1. Kaiser S, et al. AASLD 2007. Abstract 1310. 2. Gross J, et al. AASLD 2005. Abstract 60.



Bacon B, et al. AASLD 2007. Abstract 168.

DIRECT: SVR12 Rates With CIFN + RBV in PegIFN/RBV Nonresponders

9.5

No Treatment(n = 172)

SV

R12

(%

)

0

20

40

60

80

100

5.3

9 µg CIFN + RBV

(n = 245)

15 µg CIFN + RBV

(n = 242)

Modified ITT*

P = .002

0

*Patients with at least 12 weeks of viral negativity after end of treatment; RBV dosed at 1000-1200 mg/day.

P < .001



Jensen D, et al. AASLD 2007. Abstract LB4.

Patients with chronic HCV infection not

responsive topegIFN alfa-2b/

RBV therapy

PegIFN alfa-2a 180 µg/week + RBV 1000/1200 mg/day

(n = 317)

Week 48 Week 96 Week 72


(n = 156)


(n = 156)


(n = 313)

PegIFN alfa-2a360 µg/week + RBV1000/1200 mg/day

PegIFN alfa-2a360 µg/week + RBV1000/1200 mg/day

Week 12

Follow-up

Follow-up

Follow-up

Follow-up

Randomization 2:1:1:2

REPEAT: PegIFN alfa-2a Treatment of PegIFN alfa-2b Nonresponders



REPEAT: 72-Week Treatment Duration Associated With Higher SVR Rate


Pooled 72 weeks (n = 473) vs 48 weeks (n = 469)

168

72 Weeks(360/180 µg and 180 µg)

48 Weeks(360/180 µg and 180 µg)

SV

R (

%)

0

20

40

60

80

100

P = .0006

Modified ITT*

*Patients randomized who received at least 1 dose of study medication.



All treated patients (N = 942)

Yes:17%

(157/942)

No:83%

(785/942)

HCV RNA < 50 IU/mL at Week 12?

53

36

68

34

0

20

40

60

80

100

360/180 µg; 72 weeks 360/180 µg; 48 weeks 180 µg; 72 weeks 180 µg; 48 weeks

5 2 3 60

20

40

60

80

100


REPEAT: Predictive Value of HCV RNA < 50 IU/mL at Week 12



EPIC3: SVR by Previous Treatment and Response

0

20

40

PegIFN -2a + RBV (n = 375)

All(N = 2293)

Pat

ien

ts (

%)

60

IFN/RBV(n = 1423)

PegIFN -2b + RBV (n = 488)

All Previous nonresponders Previous relapsers

34

6

18

32

7

17

43

18

25

38

14

22

Poynard T, et al. EASL 2008. Abstract 988.Previous Regimen

PegIFN alfa-2b 1.5 µg/kg/week + Weight-Based RBV 800-1400 mg/day for 48 Weeks



Poynard T, et al. EASL 2008. Abstract 988.

EPIC3: Predictors of SVR

HCV GT

– GT 2/3 vs GT 1: OR = 4.9 (P < .0001)

Baseline METAVIR fibrosis score

– F2 vs F4: OR = 2.2 (P < .0001)

– F3 vs F4: OR = 1.4 (P = .0183)

Baseline HCV RNA

– ≤ 600,000 IU/mL vs > 600,000 IU/mL: OR = 1.9 (P < .0001)

Previous treatment

– IFN + RBV vs pegIFN + RBV: OR = 2.0 (P < .0001)

Previous treatment response

– Relapser vs nonresponder: OR = 3.8 (P < .0001)

Maintenance Therapy



49% of patients did not achieve 4-year event-free survival

COPILOT: Event-Free Survival With and Primary Endpoints (ITT)

Afdhal N, et al. EASL 2008. Abstract 3.

Primary endpoints more common in both colchicine and pegIFN arms in patients with portal HTN (32% and 23%, respectively) vs without portal HTN (9% and 13%, respectively)

Primary Endpoints at Year 4

0

10

20

Death OLT VaricealBleed

CTP > 2

Eve

nts

(N

o.)

Colchicine 0.6 mg twice daily (n = 55)

PegIFN alfa-2b 0.5 µg/kg/week (n = 51)

HCC

30

4 41 1

10

1

2723

13

22



HALT-C: Long-term Maintenance Therapy Study Design

Di Bisceglie A, et al. AASLD 2007. Abstract LB1.

Chronic HCV-infectedpatients with advanced

fibrosis/cirrhosisand previous nonresponse

to pegIFN/RBV

(N = 1050)

Liver biopsyLiver biopsy(1.5 years)

Liver biopsy(3.5 years)

PegIFN alfa-2a 90 µg/week(n = 517)

No treatment(n = 533)



*17% discontinued at 1.0 year and 30% discontinued at 3.5 years.

HALT-C: Long-term PegIFN alfa-2a 90 μg/week in Nonresponders No reduction in fibrosis and no difference between arms No significant difference between arms in any primary outcome

– 34.1% vs 33.8% (HR: 1.01; 95% CI: 0.81-1.26)

Di Bisceglie A, et al. AASLD 2007. Abstract LB1.

Death Decompensation HCC Increasein Fibrosis

4.613.2

3.2

31.9

6.614.3

2.8

28.2

No treatment (n = 533) PegIFN alfa-2a 90 µg/week (n = 517)*

Pat

ien

ts (

%)

Outcomes at 3.5 Years

0

20

40

60

80

100(P = NS for all comparisons)



HALT-C: Impact of Viral Suppression on Outcomes Magnitude of viral suppression during lead-in associated with a reduction in clinical

outcomes but not in fibrosis progression

Shiffman ML, et al. EASL 2008. Abstract 144.

0

20

40

60

80

100

< 2(n = 210)

2-4(n = 80)

> 4(n = 88)

Log10 Decline in HCV RNA During Lead-in

Log10 Decline in HCV RNA During Maintenance

Ou

tco

mes

(%

)

< 1 1-2 2-4 > 4

Outcomes During Maintenance Phase

60

80

100

0

20

40

273 46 24 35152 26 9 23

Fibrosis (n = 210) (P = .67)Clinical (n = 378) (P = .78)

Pat

ien

ts (

%)

Log10 Decline in HCV RNA During Maintenance

n

> 4 or (-)2-41-2< 1

Future Options for Retreatment



AlbIFN alfa-2b/RBV in Previous Nonresponders

Nelson D, et al. AASLD 2007. Abstract 51.

Nonresponders to previous IFN-based

regimens(N = 115)

AlbIFN alfa-2b 1200 µg every 4 weeks + RBV 1000-1200 mg/day

(n = 24)

48 or 72 weeks*

AlbIFN alfa-2b 900 µg every 2 weeks+ RBV 1000-1200 mg/day

(n = 23)AlbIFN alfa-2b 1200 µg every 2 weeks

+ RBV 1000-1200 mg/day(n = 24)

AlbIFN alfa-2b 1500 µg every 2 weeks+ RBV 1000-1200 mg/day

(n = 22)AlbIFN alfa-2b 1800 µg every 2 weeks

+ RBV 1000-1200 mg/day(n = 22)

*6 patients with slow virologic response had treatment extension to 72 weeks.

24-week follow-up



Overall SVR rate: 17.4%

GT1, pegIFN + RBV nonresponder SVR rate: 10.7%

SVR, % (n/N)

AlbIFN alfa-2b + RBV*

Every 4 Weeks Every 2 Weeks

1200 µg 900 µg 1200 µg 1500 µg 1800 µg

All patients 25 (6/24) 30 (7/23) 13 (3/24) 9 (2/22) 9 (2/22)

GT1, pegIFN/RBV nonresponders

15 (2/13) 15 (2/13) 13 (2/16) 7 (1/15) 6 (1/18)

Nelson D, et al. AASLD 2007. Abstract 51.

*RBV 1000-1200 mg/day based on body weight.

AlbIFN Retreatment of IFN/RBV and PegIFN/RBV Nonresponders



Boceprevir + PegIFN/RBV: Phase II Nonresponder Study, GT 1

Patients With Detectable HCV RNA or < 2 log10 Decline in HCV RNA at ≥ 12 Weeks of Previous PegIFN + RBV (N = 357)

SV

R (

%)

27-14

PegIFN alfa-2b + RBV Boceprevir* + PegIFN alfa-2b + RBV (Various Arms)

0

20

40

60

80

100

*100, 200, 400, and 800 mg TID.

Schiff E, et al. EASL 2008. Abstract 104.

Response dependent on IFN responsiveness



Telaprevir + PegIFN alfa-2a + RBV in Nonresponders or Relapsers Open-label treatment of patients from control arms of PROVE1-3 trials

Poordad F, et al. EASL 2008. Abstract 1000.

0

20

40

60

80

100

Un

det

ecta

ble

HC

V R

NA

, <

10 IU

/mL

(%

)

Week 4 (RVR)

33

50

79

Week 4 Null Responder*

Week 12 Null Responder†

Partial Responder‡

Week 20 Breakthrough

Relapser

67

100 10089

100 100 100

80

100100 100

Week 8 Week 12

*< 1 log10 drop at Week 4. †< 2 log10 drop at Week 12. ‡≥ 2 log10 drop at Week 12; detectable HCV RNA at Week 24.

Summary and Management Strategies



Principles of Retreatment

Relapsers good candidates for retreatment

– Better chance of response when compared with nonresponders

Nonresponders to suboptimal therapy (ie, standard IFN) more likely to respond to retreatment vs those previously treated with pegIFN/RBV

Nonresponders with negative predictors of response (ie, advanced fibrosis, insulin resistance) may not be good candidates for retreatment

Maintenance therapy has not been shown to be effective for reducing fibrosis progression, other disease outcomes

Promising results with new compounds, even in the setting of null response



Key Questions for HCV Patients Facing Retreatment1. What were you treated with, at what dosage, and for how

long?

2. What type of response did you have?

3. What is your GT?

4. Did you require dose reductions or treatment interruptions during previous therapy? What adverse effects caused these interruptions/dose reductions?

5. Were you overweight during previous courses of therapy?

6. Were there adherence issues?

7. Do you have any significant comorbidities/other conditions that may affect your response to treatment?

8. Did you have a good support system during previous courses of treatment? What do you have now?

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