HCV Case Study. Optimizing Outcomes with Current Therapies

HCV Case Study

Program Disclosure

• This activity has been planned and implemented in

accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education

(ACCME) through the sponsorship of Annenberg Center for Health Sciences at Eisenhower and the Chronic Liver Disease Foundation. Annenberg Center for Health Sciences at

Eisenhower is accredited by the ACCME to provide continuing medical education for physicians.

• This program is supported by educational grants from

Learning Objectives

• Describe current approaches to managing adverse events associated with current chronic hepatitis C treatments

• Optimize treatment results for patients with chronic hepatitis C utilizing current therapies

• 45 year old African American female

• History/risk factors

– BMI=32

• CHC diagnosed in 2002

• Treated with Peg-IFN/RBV in 2007

– Tolerability issues: fatigue, anemia, neutropenia, alopecia,

anxiety, depression after 6 months (treated with paroxetine)

Jackie: Disease Characteristics

• Prior relapser (early virologic response)

• Genotype 1a

• IL28B CT

• METAVIR F1 in 2007

Jackie: Baseline Labs

• Hemoglobin 12.1 g/dL • Neutrophils 1300 cells/mm3 • Platelets 200,000 cells/mm3 • Serum creatinine 0.9 mg/dL • AST/ALT 73/56 IU/L • Albumin 4.1 g/dL • Bilirubin 0.8 mg/dL • INR 0.9

Clinical Decision #1

• Would you reassess stage of fibrosis before retreatment and, if so, how?

1. No, I don’t believe it is necessary

2. Yes, I would re-biopsy the patient

Clinical Question

• Which of the following statements is most accurate?

1. Jackie has a low likelihood of success because she is African

American and IL28B CT.

2. Jackie has a very high likelihood of success because she is a

prior relapser.

3. If restaging shows cirrhosis, Jackie has a very low chance of

success.

4. Treatment is contraindicated for Jackie since she developed

86% 59% 32% 22% 15% 5% 0 20 40 60 80 100

REALIZE: SVR by Response to Previous

Peg-IFN/RBV Therapy

All Patients % SV R All T12/PR48 Placebo/PR48

Relapsers Partial Responders Null Responders

72% 46% 31% 7% 0 20 40 60 80 100 % SV R BOC* PR

Prior Relapsers Partial Responders

*Response Guided Therapy and 48 Week Arms Combined

150/208 16/51 53/115 _2/29

RESPOND 2: SVR by Response to Previous

Peg-IFN/RBV Therapy

Prior Response Trumps Other Pretreatment

Baseline Factors

• Ethnicity

• IL28B Genotype

• Baseline Viral Load

• Fibrosis Score

Jackie: On Treatment Labs

Hemoglobin (g/dL) Neutrophil Count (cells/mm3₎ HCV RNA (IU/mL) Baseline 12.1 1300 18,000,000 TW2 11.0 1100 3,300 TW4 9.5 900 Undetectable

Clinical Decision #2

• How would you manage Jackie’s anemia?

1. No change to treatment

2. Add EPO

3. Reduce RBV from 1200 mg to 1000 mg

4. Reduce RBV from 1200 mg to 600 mg

82 72 10 82 71 10 0 10 20 30 40 50 60 70 80 90 100

EOT Response SVR Relapse

% o f Pati en ts

RBV DR Arm EPO Arm

203/ 249 ₁₉₆ 19/ 178/ 249 178/ 251 205/ 251 ₁₉₇ 19/

Patients Randomized When Hb <10 g/dL

Boceprevir: No Difference in SVR Rate in Anemic

Patients Undergoing RBV DR vs EPO Use

Adapted from Poordad F et al. Abstract 1419. Poster presented at the 47th Annual Meeting of the European Association for the Study of the Liver. April 2012, Barcelona, Spain.

70 64 79 82 71 71 68 70 88 71 0 10 20 30 40 50 60 70 80 90 100 ≤4 Wks >4-8 Wks >8-12 Wks >12-16Wks >16 Wks SVR ( % ; 95 % C I)

Timing of the Start of Anemia Management

RBV DR EPO Use 38/ 54 39/ 55 58/ 90 60/ 88 49/ 62 47/ 67 18/ 22 15/ 17 15/ 21 17/ 24

SVR Rates Did Not Vary with the

Start Time of Anemia Management

Adapted from Sulkowski MS et al. Abstract 1162. Poster presented at the 47th Annual Meeting of the European Association for the Study of the Liver. April 21, 2012, Barcelona, Spain.

0 10 20 30 40 50 60 70 80 90

Any Dose reduction Received ≤600 mg/day Received 800-1000 mg/day Never reduced T12PR PR 74% 74% 75% 79% 47% 42% 54% 46% SVR , n /N (% ) RBV Dose Reductions 329/ 446 291/ 395 38/ 51 346/ 439 29/ 62 16/ 38 13/ 24 134/ 292

SVR Rates in Treatment Naïve Patients

by RBV Dose/Day

Jackie: On Treatment Labs

Hemoglobin (g/dL) Neutrophil Count (cells/mm3₎ HCV RNA (IU/mL) Action Baseline 12.1 1300 18,000,000 TW2 11.0 1100 3,300 TW4 9.5 900 Undetectable Decreased RBV (1200 to 600 mg/day) TW6 10.0 850 Undetectable TW8 10.4 900 Undetectable TW12 10.9 900 Undetectable Increased RBV (600 to 800 mg/day) TW16 11.5 1050 Undetectable Increased RBV (800 to 1000 mg/day)

Conclusions

• Many chronic hepatitis c patients are good candidates for treatment today

• Treatment outcomes with current treatments can be optimized with appropriate management/interventions