Improving Treatment Success Rates for HCV in a Managed Care Setting

Transcription

1 Improving Treatment Success Rates for HCV in a Managed Care Setting Bruce R. Bacon, MD James F. King MD Endowed Chair in Gastroenterology Professor of Internal Medicine Division of Gastroenterology and Hepatology Saint Louis University Liver Center Saint Louis University School of Medicine St. Louis, MO

2 Faculty Disclosure The faculty reported the following financial relationships or relationships to products or devices they or their spouse/ life partner have with commercial interests related to the content of this CME activity: Bruce R. Bacon, MD Consultant Fees: Schering Plough/Merck; Gilead Sciences; Three Rivers Pharmaceuticals; Valeant; Vertex; Human Genome Sciences Fees for Non-CME Services Received Directly from a Commercial Interest or their Agents: Schering Plough/Merck; Gilead Sciences; Three Rivers Pharmaceuticals; Novartis; ISIS Contracted Research: Schering Plough/Merck; Roche Laboratories; Gilead Sciences; Bristol-Myers Squibb; Three Rivers Pharmaceuticals; Valeant; Vertex; Human Genome Sciences; Wyeth; Romark Laboratories

3 Objective Assess the clinical challenges of managing patients g g g p with hepatitis C virus (HCV) within a managed care setting

4 Agenda Status update: hepatitis C virus (HCV) in 2011 Complications and mortality of chronic HCV Effect of treatment on long-term morbidity and mortality Importance of adherence Impact of new agents on HCV treatment in managed care Summary

5 HCV Status Update

6 Majority of Patients Infected With HCV Progress to Chronic Disease Incubation Period: Days Average of 45 Days Acutely Infected Persons 20% to 30% Develop Symptoms 75% to 80% of Newly Infected Develop Chronic HCV Infections 60% to 70% of Those With Chronic HCV Infections Develop Chronic Liver Disease 10% to 20% With Chronic Liver Disease Develop Cirrhosis Over 20 to 30 Years Decompensated Cirrhosis 5-year Survival Rate: 50% Hepatocellular Carcinoma: 1-4% per Year 4% Annual Death Rate Post-Cirrhosis Chen SL, Morgan TR. Int J Med Sci. 2006;3: Seeff LB, et al. Hepatology. 2002;36(suppl):S35-S46.

7 HCV Is Nearly 4 Times as Prevalent as HIV and HBV ~ M er Infec cted Numb 1.1 M Undiagnosed Diagnosed ~ M HBV=hepatitis B virus. HCV=hepatitis C virus. HIV=human immunodeficiency virus. Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C Available at: Accessed April 7, 2011.

8 Prevalence of Chronic Hepatitis C Global prevalence: ~170,000,000, cases In the United States: 5 million exposed 3.2 million chronically infected Only 25% of these are aware of their HCV status Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C Accessed April 7, 2011.

9 Majority of Those With Chronic HCV Are Baby Boomers Decade of Birth Milliman Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease Accessed April 7, 2011.

10 Complications and Mortality of Chronic HCV

11 Cirrhosis Due to HCV Expected to Peak Over the Next Decade Numbe er of Patie ents 1,200,000 1,000,000, 800, , , ,000 25% of patients with HCV currently have cirrhosis 37% of patients with HCV are projected to develop cirrhosis by 2020, peaking at 1 million Year Adapted from Davis GL, et al. Gastroenterology. 2010;138:

12 Although a High Number of Men With Chronic HCV are Projected to Develop Cirrhosis. irrhosis eloping C cent Deve Perc Years since infection Age at Infection (Years) Davis GL, et al. Gastroenterology. 2010;138:

13 A Large Number of Women With Chronic HCV Are Projected to Develop Cirrhosis as Well Per rcent Dev veloping Cirrhosis Years since infection 0.5% Age at Infection (Years) Davis GL, et al. Gastroenterology. 2010;138:

14 Complications of Cirrhosis Expected to Increase Over the Next Decade Number of Cases s 160, , , ,000 80,000 60,000 40,000 Decompensated Cirrhosis 20,000 Hepatocellular Cancer Year Davis GL, et al. Gastroenterology. 2010;138:

15 Men With HCV Have a Greater Burden of Disease Than Women Men infected before age 50 show more rapid rates of progression, accounting for 74% of cirrhosis cases in 2009 Women infected before age 50 show slower rates of progression and lower risk for developing chronic infection; only 16% had progressed to cirrhosis by 2009 Cirrhosis Prevalence by Sex and Age at Initial HCV Diagnosis sis V s of Cirrho s With HCV o. of Cases in Patients No 1,200,000 1,000, , , , ,000 Men (age at infection, years) > Women (age at infection, years) > Men Women Davis GL, et al. Gastroenterology. 2010;138:

16 Failure to Achieve SVR Causes Worsening of Liver Disease Cumulat tive Rate of First Clinica al Outcom me (%) SVR=sustain virologic response. Morgan TR, et al. Hepatology. 2010;52: Time (Years)

17 Mortality Rate Due to HCV in People Over 35 Years 123% increase in HCV mortality rates between Age Year Aging of the high prevalence birth cohort ( ) 1964) may be reflected in declining mortality seen in the age group and an increase in mortality in the age group Wise M, et al. Hepatology. 2008;47:

18 Effect of Treatment on Long-term Morbidity and Mortality

19 Why Treat Chronic Hepatitis C? The disease HCV is common, chronic, and potentially progressive Complications are becoming more common Liver failure Hepatocellular carcinoma (HCC) The treatment Viral cure, or sustained virologic i response (SVR), is achievable SVR associated with histologic improvement and gradual regression of fibrosis i 1 SVR leads to lower risk for liver failure and HCC, and improved survival 2,3 1. Poynard T, et al. Gastroenterology. 2002;122: Craxi A, et al. Clin Liver Dis. 2005;9: Shiratori Y, et al. Ann Intern Med. 2005;142:

20 There Is a Need to Treat More Patients and to Achieve Improved Outcomes Disease burden is high and getting g worse New therapies are becoming available Must increase screening efforts to identify more patients for treatment Increased sustained virologic response (SVR) means improved outcome Adherence leads to an improved SVR McHutchinson JG, et al. Am J Manag Care. 2007;S327-S336.

21 Lower Mortality Results From Improved and Increased HCV Treatment Mo ortality 40% % of Population Treated Increasing SVR Rate Bacchus LI, et al. Clin Gastroenterol Hepatol Mar 10. [Epub ahead of print]

22 Successful Treatment Equals SVR Sustained virologic response (SVR) undetectable plasma HCV RNA 24 Weeks after completion of treatment is the goal of therapy 1,2 Start of Treatment End of Treatment IU/mL) HCV RNA (log 10 SVR Undetectable HCV RNA in Plasma Viral Eradication Wks Post-treatment Weeks 1. Sherman KE, et al. Hepatology. 2007; 46: Ghany MG, et al. Hepatology. 2009;49:

23 SVR Equals Cure Nearly 100% of Patients Who Achieve SVR Remain Undetectable During Long-term Follow-up 1-4 % of Pa atients With SVR Duration of Follow-up 1. Swain MG, et al. Gastroenterology. 2010;139: Gianni EG, et al. Aliment Pharmacol Ther. 2010;31: Maylin S, et al. Gastroenterology. 2008;135: George SL, et al. Hepatology. 2009;49:

24 Histologic Improvement After Successful Anti-HCV Therapy Pretreatment biopsy: Trichrome stain with Ishak stage 3 fibrosis (portal-to-portal p bridging) g) Long-term term, follow-up biopsy obtained from the same patient 57 months after end of treatment: Trichrome stain with Ishak stage 1 fibrosis George S, et al. Hepatology. 2009;49:

25 Patient Characteristics Predictive of SVR Patients with these characteristics may have a higher likelihood of achieving SVR following treatment with pegylated-interferon and ribavirin: Non-African American race 12 1,2 Age <40 years 1 Lower body weight ( 75 kg) 1,2 Absence of insulin resistance 1,2 Normal fasting glucose level 2 Polymorphism in IL-28B gene 3 1. Ghany MG, et al. Hepatology. 2009;49: McHutchison JG, et al. N Engl J Med. 2009;361: Thompson AJ, et al. Gastroenterology. 2010;139:

26 Disease Characteristics Predictive of SVR Patients with these disease characteristics may have a higher likelihood of achieving SVR with pegylated-interferon and ribavirin: Non-genotype 1-HCV 1 Low baseline viral load ( 600,000 IU/mL) 1,2 Absence of bridging g fibrosis/cirrhosis 1,2 Absence of steatosis 2 Elevated baseline ALT (3xULN) 1 1. Ghany MG, et al. Hepatology. 2009;49: McHutchison JG, et al. N Engl J Med. 2009;361: Thompson AJ, et al. Gastroenterology. 2010;139:

27 Viral Kinetics Predict SVR RNA Leve els 91% Achieved SVR 70% Achieved SVR 45% Achieved SVR HCV Weeks After Start of Treatment Undetectable HCV RNA Fried MW, et al. J Hepatol Nov 23. [Epub ahead of print]

28 RVR Predicts SVR HCV RN NA (log 10 IU U/mL) Undetectable HCV RNA in Plasma 91% of patients who reach undetectable HCV RNA at Week 4 achieved SVR Start of Treatment Week 4 of Treatment End of Treatment 24 Weeks Post-treatment RVR=rapid virologic response. Fried MW, et al. J Hepatol Nov 23. [Epub ahead of print]

29 Importance of Adherence to Treatment

30 Adherence to Therapy Is Critically Important to Improving Outcomes Treatment Peg-interferon 1 Ribavirin 2 Dosing Q week BID Protease inhibitor boceprevir 3 TID teleprevir 4 Q8 hours 1. Peginterferon alfa-2a Prescribing Information. Genentech, Inc. February Ribavirin prescribing information. Accessed April 11, Bacon B, et al. N Engl J Med. 2011;364: Jacobson IM, et al. Presented at the 61st AASLD. Boston, MA. October 29-November 2, Abstract 211.

31 Self-reported Adherence to Treatment With Peg-IFN and RBV Patients (%) (n=369) (n=348) (n=327) (n=208) (n=170) Weeks on Treatment Smith SR, et al. Ann Pharmacother. 2007;41:

32 A Multidisciplinary Approach Is Required to Enhance Patient Adherence Educate and empower patients about disease state Anticipate and manage medication side effects Identify financial and psychosocial resources Increased adherence, which results in effective treatment Improve Dosing Strategies Gujral H, et al. Clev Clin J Med. 2004;71:S33-S37.

33 Impact of New Agents on HCV Treatment in Managed Care

34 HCV Treatment Continues to Evolve Infergen 10/97 Rebetol 6/98 PegIntron 1/01 Copegus 12/02 Pegasys 10/02 Single-source Ribavirin 1/03 Ribasphere 4/04 Expected telepravir and boceprivir review Prior to

35 Current and Emerging Therapies Will Be Combined to Increase SVR Newer agents such as the oral protease inhibitors are emerging However, treatment regimens will continue to rely on interferon and ribavirin (RBV) for at least another few years Regardless of the regimen, patients must be adherent for efficacy and to prevent/limit resistance Asselah T, Marcellin P. Liver Int. 201;(31 Suppl 1):68-77.

36 Ribavirin Is Critical to the Success of HCV Combination Therapy RBV will continue to play an important role in successful antiviral therapy Antiviral and immunomodulatory activity Reduced d likelihood lih 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 ftreatment? t t? Dusheiko G, et al. Antivir Ther. 2008;13(suppl 1):23-30.

37 Cumulative RBV Exposure >60% of the Initially-assigned Dose Treatment Weeks 0-12 vs Weeks 0-48 Sulkowski M, et al. J Hepatol. 2008; 48:S370. Sulkowski M, et al. Gastroenterol. 2010; 139:

38 Milestones in IFN-based HCV Therapy SV VR (%) RBV in Combination With Interferon- Led to Marked Improvements in SVR Rate* 1990s IFNα-2b 24 wks PegIFNα-2a 48 wks IFNα-2b+RBV 24 wks 2000s PegIFNα-2b + RBV 48 wks IFNa-2b=interferon alpha-2b. PegIFNa-2a=peglyated interferon alpha-2a. RBV=ribavirin. SVR=sustained virologic response. *In patients infected with HCV genotype 1, high viral load. Hayashi N, et al. J Gastroenterol. 2006;41:17-27.

39 Reduction of RBV Dose Associated With Stepwise Increase in Relapse Rate Mean RBV Dose Significantly ifi Correlated With Relapse (P<.0001) se (%) Relaps Mean RBV Dose (mg/kg/d) Hiramatsu N, et al. J Vir Hepat. 2009;16:

40 RBV Is Critical for Protease Inhibitor Combination Therapy PROVE-2 1 PROVE-3 2 SPRINT-1 3 SVR (%) % 24% 53 29% T12PR12 (n=82) T12P12 (n=78) T24PR48 (n=13) T24P24 (n=111) PBR48 (n=103) PBLowR48 (n=59) PROVE=Protease Inhibition for Viral Evaluation. SPRINT=Serine Protease Inhibitor Therapy. 1. Hezode C, et al. N Engl J Med. 2009;360: McHutchison JG, et al. N Engl J Med. 2010;362: Kwo P, et al. Lancet. 2010; 376: = Telaprevir + Peg-Interferon + Ribavirin = Telaprevir + Peg-Interferon = Boceprevir + Peg-Interferon + Ribavirin = Boceprevir + Peg-Interferon + Low-dose Ribavirin (400mg-1000mg/d)

41 Impact of Newer Agents on HCV Treatment in Managed Care Approval of new agents such as the oral protease inhibitors will require HCV treatment guidelines to be updated New guidelines will require managed care reimbursement algorithms to be created to define eligibility criteria Stakeholders should work to reduce the lag following approval of these new agents, the revision HCV practice guidelines, and subsequent managed care reimbursement guidance McHutchinson JG, et al. Am J Manag Care. 2007;S327-S336.

42 Summary

43 Summary Prevalence of HCV increasing Disease burden can be reduced through better patient identification and treatment designed to increase SVR Increased SVR equals improved outcomes Adherence is critical for increasing SVR Regimens that combine ribavirin with a protease inhibitor improve SVR Availability of new agents will require treatment guidelines and managed care reimbursement algorithms to be revised