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Marc Bourlière, MD
Graham R. Foster, FRCP, PhD
Managing Cirrhotic HCV Patients:
Whom to Treat, How to Treat
This program i...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
About These Slides
 Users are ...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Disclosures
Marc Bourlière, MD,...
Which Cirrhotic Patients
Should be Treated?
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Cirrhosis: A Continuous Spectru...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Severity of Disease Increases N...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Benefits and Challenges of Curr...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Efficacy of Triple Therapy in T...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
CUPIC: High-Risk Patients Less ...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
HCV Decompensated Cirrhosis:
Tr...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
100
NEUTRINO: Virologic Respons...
clinicaloptions.com/hepatitis
HCV Phase III Studies and Approved Agents
QUEST-2: SVR12 by Subtype and Fibrosis
Level With ...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
FISSION: SVR12 by GT and Cirrho...
clinicaloptions.com/hepatitis
AASLD 2013: HCV Investigational Agents
COSMOS: SVR12 in F3/4 GT 1 Pts
Receiving Simeprevir +...
clinicaloptions.com/hepatitis
AASLD 2013: HCV Investigational Agents
Promising IFN-Free Regimens in
Genotype 1 Cirrhotic P...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Take Home Points
 Cirrhotic pa...
Ensuring Informed
Decision-Making When
Treating or Deferring in
Cirrhotic Patients
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Ensuring Informed Decision Maki...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Survival Outcomes in Pts With C...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
CUPIC: Risk–Benefit of Achievin...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Real-life Experience in Cirrhot...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Factors Associated With Hepatic...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Factors Associated With Greater...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Take Home Points
 HCV treatmen...
Optimizing Outcomes in
Patients Who Wish
To Be Treated
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Pretreatment Optimization Strat...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
ENABLE: Eltrombopag Enables HCV...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
On-Treatment Optimization Strat...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Wk 2 Hb Level Predicts Subseque...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
CUPIC: Anemia Management in Cir...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
SVR by RBV Dose Reduction Durin...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Similar SVR When RBV Dose Modif...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
ENABLE: Higher SVR Rates in Pat...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
ENABLE: Safety Considerations i...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Increased Risk of Renal Impairm...
clinicaloptions.com/hepatitis
Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat
Take Home Points
 Hb level sho...
Go Online for More Insights
Into the Management of
Cirrhotic HCV Patients
Downloadable slideset
clinicaloptions.com/treatn...
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Managing cirrhotic HCV patients. Whom to treat, how to treat.2014

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Managing cirrhotic HCV patients. Whom to treat, how to treat.2014

  1. 1. Marc Bourlière, MD Graham R. Foster, FRCP, PhD Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat This program is supported by an educational grant from
  2. 2. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.
  3. 3. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Disclosures Marc Bourlière, MD, has disclosed that he has received consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, GlaxoSmithKline, and Roche. Graham R. Foster, FRCP, PhD, has disclosed that he has received funds for research support from Idenix and Spring Bank; consulting fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Idenix, Janssen, Merck, Novartis, and Roche; and fees for non-CME/CE services received directly from a commercial interest or their agents (eg, speaker bureaus) from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, Novartis, and Roche The following planners and managers, Laura Excell, ND, NP, MS, MA, LPC, NCC; Trace Hutchison, PharmD; Samantha Mattiucci, PharmD, CCMEP; Jan Schultz, RN, MSN, CCMEP; Patricia Staples, MSN, NP-C, CCRN; and Eric D. Peterson, EdM, FACEHP, hereby state that they or their spouse/life partner do not have any financial relationships or relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months.
  4. 4. Which Cirrhotic Patients Should be Treated?
  5. 5. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Cirrhosis: A Continuous Spectrum of Disease ESLD Child-Pugh B Portal hypertension – high risk Cirrhosis – treatment candidate Liver disease is not optimally represented by Child-Pugh stage (A, B, or C) or MELD score
  6. 6. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Severity of Disease Increases Need for HCV Therapy but Also Impairs Response  May not need immediate treatment  BUT • Easier to treat • High likelihood of response Advanced disease/ cirrhosis Mild disease  Greater need for treatment  BUT • Response to current IFN- based therapy may be impaired
  7. 7. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Benefits and Challenges of Currently Approved HCV Therapies  Currently approved HCV regimens are largely interferon-based – Genotype 1 – PegIFN/RBV + boceprevir – PegIFN/RBV + sofosbuvir – Genotype 2 or 3 – PegIFN/RBV or sofosbuvir + RBV – Genotype 4 – PegIFN/RBV ± sofosbuvir  Combination of DAA agent with pegIFN/RBV has dramatically increased rates of SVR  However, cirrhotic patients are at increased risk for hematologic side effects (eg, thrombocytopenia and anemia), other adverse effects of treatment, and worsening liver function – PegIFN/RBV + telaprevir – PegIFN/RBV + simeprevir
  8. 8. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Efficacy of Triple Therapy in Tx-Exp Patients: Clinical Trials vs Real Life* 1. Zeuzem S, et al. N Engl J Med. 2011;364:2417-2428. 2. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. 3. Fontaine H, et al. EASL 2013. Abstract 60. 4. Fontaine H, et al. AFEF 2013. Abstract 26. 5. Vierling JM, et al. DDW 2013. Abstract 869c. Relapsers R EA LIZE[1] EAP[3] R EA LIZE[1] C U PIC[4] C U PIC[4] R ESPO N D 2[2] Null Responders R EA LIZE[1] EAP[3] R EA LIZE[1] C U PIC[4] C U PIC[4] PR O VID E[5] SVR(%) Telaprevir F0-4 F4 F3/4 F4 F0-4 F4 F3/4 F4 *Cross-comparison of studies cannot be carried out 100 80 60 40 20 0 Boceprevir 83 69 84 54 7453 29 41 28 29 19 0
  9. 9. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat CUPIC: High-Risk Patients Less Likely to Achieve SVR  CUPIC enrolled treatment-experienced patients with compensated cirrhosis and notable risk factors – Patients achieved high SVR rates with TVR or BOC plus pegIFN/RBV  Patients with cirrhosis who present with significant risk factors require careful monitoring when treated with pegIFN/RBV Factors Platelet Count ≤ 100,000/mm3 Platelet Count > 100,000/mm3 Albumin < 35 g/L N 37 31 Complications, n (%) 19 (51.4) 5 (16.1) SVR12, n (%) 10 (27.0) 9 (29.0) Albumin ≥ 35 g/L N 74 305 Complications, n (%) 9 (12.2) 19 (6.2) SVR12, n (%) 27 (36.5) 168 (54.9) Fontaine H, et al. AFEF 2013. Abstract 26.
  10. 10. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat HCV Decompensated Cirrhosis: Treatment With PegIFN/RBV  Most in need of treatment (5-yr survival rate: 50%)  SVR rates ranged: – 7% to 16% in genotypes 1-4[1,2] – 44% to 57% in genotypes 2/3 [1,2]  Treatment limitation – Higher risk of infection and deaths related to infection[1] – More frequent adverse effects in Child-Pugh C (MELD > 18)[3]  Treatment benefit – Lower rate of decompensation during follow-up[1,4] – Reduced mortality in responders[1,4] 1. Iacobellis A, et al. J Hepatol. 2007;46:206-212. 2. Iacobellis A, et al. Aliment Pharmacol Ther. 2009;27:1081-1085. 3. Forns X, et al. J Hepatol. 2003;39:389-396. 4. Fattovich G, et al. Gastroenterology. 1997;112:463-472.
  11. 11. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat 100 NEUTRINO: Virologic Response by Cirrhosis Status With Sofosbuvir + P/R Lawitz E, et al. N Engl J Med. 2013;368:1878-1887.  Open-label, single-arm, phase III study  Sofosbuvir 400 mg QD + PegIFN/RBV for 12 wks  Treatment-naive patients with GT 1/4/5/6 HCV – 17% cirrhosis; platelets ≥ 90,000/mm3 – 89% GT 1, 9% GT 4, < 1% GT 5, 2% GT 6 SVR12(%) 92 80 252/ 273 43/54 80 60 40 20 0 n/N = GT 1/4/5/6 CirrhoticNoncirrhotic
  12. 12. clinicaloptions.com/hepatitis HCV Phase III Studies and Approved Agents QUEST-2: SVR12 by Subtype and Fibrosis Level With Simeprevir + PegIFN/RBV RGT  Randomized, double-blind, placebo-controlled phase III trial in GT 1 treatment- naive patients  Treatment regimens: – Placebo + pegIFN/RBV for 12 wks, followed by pegIFN/RBV for 36 wks – Simeprevir + pegIFN/RBV for 12 wks, followed by pegIFN/RBV for 12-36 wks (RGT) Manns M, et al. EASL 2013. Abstract 1413. No Cirrhosis Cirrhosis SMV + pegIFN/RBV PegIFN/RBV 189/ 231 61/ 119 11/ 17 6/ 15 n/N = 100 80 60 40 20 0 SVR12(%) 82 65 51 40
  13. 13. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat FISSION: SVR12 by GT and Cirrhosis Status With SOF + RBV vs PegIFN/RBV  Randomized, controlled, open-label phase III noninferiority trial  Sofosbuvir + RBV for 12 wks vs pegIFN + RBV for 24 wks  Treatment-naive patients with GT 2/3 HCV – 20% to 21% cirrhosis; platelets > 75,000/mm3 ;28% GT 2, 72% GT 3 Lawitz E, et al. N Engl J Med. 2013;368:1878-1887. Gane E, et al. AASLD 2013. Abstract 5. GT 2 GT 3 SVR12(%) No Cirrhosis No CirrhosisCirrhosis Cirrhosis 58/59 44/54 10/11 8/13 •89/145 99/139 •13/38 11/37n/N = 100 80 60 40 20 0 98 82 91 62 61 71 34 30 Sofosbuvir + RBV PegIFN + RBV
  14. 14. clinicaloptions.com/hepatitis AASLD 2013: HCV Investigational Agents COSMOS: SVR12 in F3/4 GT 1 Pts Receiving Simeprevir + Sofosbuvir ± RBV Lawitz E, et al. EASL 2014. Abstract 165.  Open-label, randomized phase IIa study of simeprevir + sofosbuvir with or without RBV for 12 or 24 wks in cirrhotic and noncirrhotic GT 1 treatment naive or previous null responders  Primary endpoint: SVR12 SMV/SOF ± RBV SMV/SOF + RBV SMV/SOF + RBV SMV/SOF SMV/SOF 24 Wks 12 Wks Overall 16/16 12/12 6/6 9/9 15/16 10/11 7/7 6/7 44/45 37/39 F3 fibrosis F4 fibrosis SVR12(%) 100 80 60 40 20 0 100 100 100 100 100 94 91 98 86 95 n/N =
  15. 15. clinicaloptions.com/hepatitis AASLD 2013: HCV Investigational Agents Promising IFN-Free Regimens in Genotype 1 Cirrhotic Patients Regimen SVR12, % Tx Naive Tx Exp PI Failure Sofosbuvir + ledipasvir[1,2] --- 70 (N = 10) 91 (N = 11) Sofosbuvir + ledipasvir + RBV[1,2] --- 100 (N = 25) 100 (N = 11) Sofosbuvir + ledipasvir + GS-9669[1] --- 100 (N = 26) --- Daclatasvir + asunaprevir[3] * 90 (N = 203)† 82 (N = 205)† --- Daclatasvir + asunaprevir + BMS-791325 75 mg[4] 94 (N = 16) --- --- Daclatasvir + asunaprevir + BMS-791325 150 mg[4] 89 (N = 18) --- --- ABT-450/ritonavir/ombitasvir + dasabuvir + RBV[5] 94 (N = 86) 87-97 (N = 122) --- ABT-450/ritonavir/ombitasvir + dasabuvir + RBV[5] * 95 (N = 74) 95-100 (N = 98) --- 1. Gane EJ, et al. AASLD 2013. Abstract 73. 2. Lawitz. E et al. AASLD 2013, Abstract 215. 3. Manns M, et al. EASL 2014. Abstract 166. 4. Everson GT, et al. Gastroenterol. 2014;146:420-429. 5. Poordad F, et al. N Engl J Med. 2014;[Epub ahead of print]. *Treatment duration: 24 weeks; all others 12 weeks. † Genotype 1b HCV-infected patients only
  16. 16. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Take Home Points  Cirrhotic patients are the most in need for HCV treatment  Child-Pugh A patients should be strongly advised to undergo therapy  More advanced cirrhosis should be treated with caution on a case-by-case basis  Newest DAA + pegIFN/RBV combinations increase SVR in cirrhotic patients  IFN-free DAA regimens demonstrate significant potency in cirrhotic patients
  17. 17. Ensuring Informed Decision-Making When Treating or Deferring in Cirrhotic Patients
  18. 18. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Ensuring Informed Decision Making for Cirrhotic Patients  Patients should be fully informed of the potential risks of treatment or deferral Strategy Potential Benefits Potential Risks Immediate treatment  SVR and prevention of disease progression  Serious adverse events (death, infection, severe hepatic decompensation) Deferring treatment  Achieving SVR with a future regimen with fewer adverse events  Liver-related mortality  Need for liver transplantation  Liver failure  Development of HCC
  19. 19. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Survival Outcomes in Pts With CHC and Advanced Fibrosis With/Without SVR Van der Meer AJ, et al. JAMA. 2012;308:2584-2593. 30 20 10 0 0 All-Cause Mortality(%) 1 2 3 4 5 6 7 8 9 10 Yrs All-Cause Mortality P < .001 Without SVR With SVR Pts at Risk, n Without SVR With SVR 405 192 393 181 382 168 363 162 344 155 317 144 295 125 250 88 207 56 164 40 135 28 30 20 10 0 0 Liver-Related MortalityorLiver Transplantation(%) 1 2 3 4 5 6 7 8 9 10 Yrs Liver-Related Mortality or Liver Transplantation P < .001 Without SVR With SVR Pts at Risk, n Without SVR With SVR 405 192 392 181 380 168 358 162 334 155 305 144 277 125 229 88 187 56 146 40 119 28 30 20 10 0 0 Hepatocellular Carcinoma(%) 1 2 3 4 5 6 7 8 9 10 Yrs Hepatocellular Carcinoma P < .001 Without SVR With SVR Pts at Risk, n Without SVR With SVR 405 192 390 181 375 167 349 161 326 152 294 142 269 124 229 86 191 54 151 39 122 27 30 20 10 0 0 LiverFailure(%) 1 2 3 4 5 6 7 8 9 10 Yrs Liver Failure P < .001 Without SVR With SVR Pts at Risk, n Without SVR With SVR 405 192 384 180 361 166 337 160 314 152 288 141 259 123 216 88 184 56 143 40 113 28
  20. 20. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat CUPIC: Risk–Benefit of Achieving SVR12 vs Developing Serious Complications Platelet Count ≤ 100,000/mm3 Platelet Count > 100,000/mm3 Albumin < 35 g/L Serious AEs >> SVR SVR > Serious AEs Albumin ≥ 35 g/L SVR > Serious AEs SVR >> Serious AEs Fontaine H, et al. AFEF 2013. Abstract 26.
  21. 21. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Real-life Experience in Cirrhotic Patients  33 cirrhotic patients received TVR and 15 received BOC  Almost all patients (22/23; 96%) with Child-Pugh score > 5 and/or baseline platelets < 110,000/µL (Group A/B) had either treatment failure or SAE Outcome, % Group A Platelets < 110,000/µL and Child-Pugh > 5 (n = 7) Group B Platelets < 110,000/µL or Child-Pugh > 5 (n = 16) Group C Platelets ≥ 110,000/µL and Child-Pugh = 5 (n = 20) Treatment failure 100 69 30 SAE 57 63 25 Treatment failure or SAE 100 94 50 Massoumy B, et al. EASL 2013. Abstract 857.
  22. 22. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Factors Associated With Hepatic Decompensation During P/R Therapy  In retrospective cohort study, 68 pts with HCV-associated liver cirrhosis treated with pegIFN/RBV – Mean age: 51 yrs; baseline MELD: 9.2 (5-20)  Hepatic decompensation observed in 36.8% of patients  Baseline MELD score associated with hepatic decompensation in multivariate analysis: OR: 1.56 (1.18-2.07; P = .002) Dultz G, et al. PLoS One. 2013;8:e71262. 100 80 60 0 6 Frequencyof Decompensation(%) 40 20 8 10 12 14 16 18 20 MELD Score 22% 59% 83%
  23. 23. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Factors Associated With Greater Benefit or Greater Risk of Treatment in Cirrhotics Factors Associated With Greater Benefit of Therapy Factors Associated With Greater Risks of Therapy  ↓ Child-Pugh score  ↓ MELD score  ↑ Platelet count  ↑ Albumin level  ↓ Age  ↑ Child-Pugh score  ↑ MELD score  ↓ Platelet count  ↓ Albumin level  ↑ Age
  24. 24. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Take Home Points  HCV treatment in cirrhotic patients is associated with high rates of treatment-related adverse events and lower response rates than in patients with less advanced disease  However, immediate treatment could lead to SVR and prevent disease progression  For every patient, an informed choice is critical
  25. 25. Optimizing Outcomes in Patients Who Wish To Be Treated
  26. 26. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Pretreatment Optimization Strategies  Lifestyle changes  Pretreatment initiation of eltrombopag  Ultrasound to exclude ascites  Check recent endoscopy report  Consider antibiotics in cirrhotic patients with upper gastrointestinal bleeding[1] 1. Chavez-Tapia NC, et al. Cochrane Database Syst Rev. 2010;9:CD002907.
  27. 27. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat ENABLE: Eltrombopag Enables HCV Tx Initiation Through Higher Platelet Counts  Patients with platelet counts < 75,000/µL received open-label eltrombopag in a dose-escalating fashion dependent on platelet response for 2-9 wks until platelet counts increased sufficiently to initiate antiviral therapy 773/ 805 694/ 715 ENABLE-1 (90,000/µL) ENABLE-2 (100,000/µL) 9697100 80 60 40 20 0 PatientsAchievingRequired PlateletThreshold(%) Afdhal NH, et al. Gastroenterology. 2014;146:442-452. Adverse Event, % ENABLE-1 (N = 715) ENABLE-2 (N = 805) Any 37 34 Grade ≥ 3 adverse events 2 3  Blood bilirubin level increased < 1 < 1  Hepatic neoplasm malignant <1 <1 Serious adverse events 1 1  Hepatic neoplasm malignant < 1 < 1
  28. 28. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat On-Treatment Optimization Strategies  Anemia management – RBV dose reductions – Addition of erythropoietin – Transfusions  Management of thrombocytopenia – On-treatment initiation of eltrombopag  Monitoring of renal function
  29. 29. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Wk 2 Hb Level Predicts Subsequent Onset of Anemia (REALIZE: TVR + PegIFN/RBV) PtsWithAnemiaAfterWk2(%) 10/13 19/4832/60 15/59 7/5818/27 < 11 11 to < 12 12 to < 30 13 to <14 14 to 15 ≥ 15 Hb at Wk 2 (g/dL) Proportion of Patients With Occurrence of Hb < 10 g/dL After Wk 2 According to Hb Level at Wk 2 Zeuzem S, et al. J Hepatol. 2014;[Epub ahead of print]. 100 80 60 40 20 0 77 67 53 40 25 12
  30. 30. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat CUPIC: Anemia Management in Cirrhotics According to Age 22/ 221 Grade 3/4 Anemia Transfusions 10 100 80 60 40 20 0 Patients(%) Hezode C, et al. AASLD 2013. Abstract 1845. < 65 yrs ≥ 65 yrs 21 16/ 78 26/ 221 12 35 27/ 78 106/ 221 48 81 63/ 78 EPO P = .028 P < .001 P < .001 Grade 3/4 Anemia Transfusions 7 100 80 60 40 20 0 18 8/ 44 16/ 168 10 20 9/ 44 89/ 168 53 68 30/ 44 EPO P = .032 P ≤ .063 P = .088 Telaprevir Boceprevir 11/168
  31. 31. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat SVR by RBV Dose Reduction During First 4 Wks of Tx and HCV RNA Status  Retrospective analysis of ADVANCE/ILLUMINATE studies of TVR + pegIFN/RBV  SVR rates in pts with vs without RBV dose reduction between Wks 0-4 of Tx, analyzed by whether HCV RNA was detectable or undetectable 120/ 176 40/ 45 Undetectable HCV RNA Detectable HCV RNA 68 89 100 80 60 40 20 0 SVR(%) Sulkowski MS, et al. EASL 2012. Abstract 1162. 347/ 405 86 168/ 259 65 RBV dose reduction No RBV dose reduction
  32. 32. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Similar SVR When RBV Dose Modification or EPO Used to Manage Anemia on BOC  500/687 treatment-naive GT 1 pts on BOC-based therapy developed anemia (Hb ≤ 10 g/dL or expected to reach that nadir before next visit)  Randomized to EPO (40,000 units/wk SC) or RBV dose reduction (by 200-400 mg/day) 178/ 251 178/ 249 RBV Dose Reduction EPO Use 71 72 100 80 60 40 20 0 SVR(%) Poordad F, et al. Gastroenterology. 2013;145:1035-1044.
  33. 33. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat ENABLE: Higher SVR Rates in Patients Receiving Eltrombopag vs Placebo  Patients randomized 2:1 to either placebo or eltrombopag + pegIFN alfa-2a (ENABLE-1) or placebo or eltrombopag + pegIFN alfa-2b (ENABLE-2)  Higher platelet counts in eltrombopag arms vs placebo by Wk 2 of treatment, enabling full dose of pegIFN to be maintained – ENABLE-1: 11,000/µL vs 79,000/µL 0 20 40 80 100 SVR(%) 60 32/ 232 14 ENABLE-1 ENABLE-2 103/ 449 33/ 252 96/ 506 23 13 19 Placebo Eltrombopag n/N = P = .0064 P = .0202 Afdhal NH, et al. Gastroenterology. 2014;146:442-452. – ENABLE-2: 124,000/µL vs 89,500/µL
  34. 34. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat ENABLE: Safety Considerations in Antiviral Phase  Greater proportion of placebo pts D/C HCV treatment due to AEs (27% vs 19%)  Cataracts more common in eltrombopag arm vs placebo for ENABLE-1 (8% vs 3%) but similar for ENABLE-2 (7% vs 6%)  Hepatic decompensation (ascites, hepatic encephalopathy, variceal hemorrhage, or spontaneous bacterial peritonitis) more common in eltrombopag vs placebo-treated pts (10% vs 5%)  Boxed warning: eltrombopag in combination with IFN + RBV may increase risk of hepatic decompensation 1. Afdhal NH, et al. Gastroenterology. 2014;146:442-452. AE, %[1] ENABLE-1 ENABLE-2 Placebo (n = 232) Eltrombopag (n = 449) Placebo (n = 252) Eltrombopag (n = 506) Any 97 96 93 94 Grade ≥ 3 AE 56 51 51 48 Serious AE 15 20 15 20
  35. 35. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Increased Risk of Renal Impairment With Triple Therapy Containing TVR or BOC  Observational study of 1185 patients with GFR data at baseline  Results emphasize that renal function must be assessed during treatment PR BOC PR 4.7 (10/211) 0.9 (1/109) 100 80 60 40 20 0 RenalImpairmentatWk12in PtsWithNormalRenal FunctionatBaseline(%) Mauss S, et al. EASL 2013. Abstract 872. 6.6 (38/575) TVR PR P = .0753 P = .0188 Risk Factor for Renal Insufficiency P Value Age < .001 Hypertension < .001 Diabetes < .05 Triple therapy < .05
  36. 36. clinicaloptions.com/hepatitis Managing Cirrhotic HCV Patients: Whom to Treat, How to Treat Take Home Points  Hb level should be frequently assess during treatment and anemia should be treated as early as possible – EPO and RBV dose reductions for anemia lead to similar SVR rates in BOC-treated patients  In HCV patients with platelet counts < 70,000/µL, eltrombopag may increase platelet counts to levels that allow HCV therapy to be initiated and may allow for higher SVR rates with a reduced need for pegIFN dose reductions  Renal function must be assessed during treatment
  37. 37. Go Online for More Insights Into the Management of Cirrhotic HCV Patients Downloadable slideset clinicaloptions.com/treatnow

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