After the Cure: Looking Ahead in HCV Management. Nancy Reau, MD

Transcription

1 After the Cure: Looking Ahead in HCV Management Nancy Reau, MD

2 Objectives 1. Discuss current recommendations in HCV screening, performance and limitations 2. Discuss linkage to care, hurdles and strategies for improvement 3. Discuss impact of cost on access to HCV therapy 4. Identify difficult populations to treat

3 Hepatitis C is the Most Common Blood-Borne Chronic Viral Infection in US Unaware of Infection Aware of Infection ~3,300,000 Prevalence (N) ,475, ~1,100,000 ~1,100, , , , ,000 HIV/AIDS HBV HCV 825,000 Adapted from Colvin HM, Mitchell AE. Hepatitis and liver cancer: A national strategy for prevention and control of hepatitis B and C. Washington, DC: The National Academies Press; 2010.

4 Identifying Priorities to Improve Outcomes 100% HCV Care Cascade Unaware of diagnosis 50% 32 38% 20 23% 12 18% 7 11% 5 6% Holmberg SD, et al. N Engl J Med. 2013:368(20):

5 Identifying Priorities to Improve Outcomes 100% HCV Care Cascade Eliminated by Effective Therapy Unaware of diagnosis 50% 32 38% 20 23% 12 18% 7 11% 5 6% Holmberg SD, et al. N Engl J Med. 2013:368(20):

6 Definition of Difficult Has Changed Renal Failure Drug Drug interactions Decompensated cirrhosis DAA failure 6

7 Identifying Priorities to Improve Outcomes 100% 50% HCV Care Cascade Unaware of diagnosis Screen + Confirm + Communicate 32 38% 20 23% 12 18% 7 11% 5 6% Holmberg SD, et al. N Engl J Med. 2013:368(20):

8 Evolution of Screening 1998, the Centers for Disease Control and Prevention published risk-based screening recommendations 45% to 85% of those infected remain unaware of their HCV status 72% of HCV-positive injection drug users are unaware MMWR Recomm Rep 2012;61(RR-4): mmwrhtml/rr6104a1.htm

9 Evolution of Screening CDC Screening Recommendations All adults born during should have 1-time testing without prior ascertainment of HCV risk All persons identified with HCV should receive: Alcohol screening Intervention as clinically indicated Referral to appropriate care Endorsed by USFPTF and CMS CDC = Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report (MMWR). 2012;61(RR04):1-18.

10 Real-World Findings of the Burden of HCV in the US CDC analysis ~9.8 million HCV-related tests from ,207 positive HCV RNA 186,416 (68.2%) were born from Stage Fibrosis Before After 1965 All None 1.2% 9% 55% 19.5% Moderate 20% 39% 28.5% 35% Severe 38% 26% 6.7% 22% Cirrhosis 36% 21% 4% 18% Missing 5% 4.5% 5.5% 4.8% Total 8,521 86,741 29, ,076 81% with advanced fibrosis were from birth cohort Klevens M, et al. CROI Abstract 145.

11 HCV Screening of Birth Cohort Increased After CDC Call to Action; Screening Rate Fell in Non-Boomers Nationwide Medivo Lab Exchange Database Smyth C, et al. Abstract 1447 AASLD 2014

12 Acute Hepatitis C is Increasing Reported cases of acute, hepatitis C United States, Rate per 100, Rate per 100, April 24, 2015 CDC Health Alert

13 No. of Cases Per 100,000 Population Increases in HCV Infection among young persons who inject drugs (< 30 years old) Nonurban Urban * MMWR Morb Mortal Wkly Rep. 2015;64:453-8.

14 Incidence of sexually transmitted hepatitis C virus infection in HIV-positive men who have sex with men HCV seroconversion increased from an estimated rate of: 1991: 0.42/100 person-years to 2010: 1.09/100 person-years and 2012: 1.34/100 person-years Infections were attributable to high-risk behaviors including traumatic sex and sex while on methamphetamines Hagan H et al. AIDS 2015 Could PrEP work for HCV?

15 Number of Prisoners Estimated Prevalence of HCV in Federal and State Prisons and Local Jails In 2006, of the 10.7 million people Incarcerated at any point, an estimated 1.9 million were HCV-positive In 1997, of the 9.6 million people Incarcerated at any point, million were HCV-positive Adapted from: Rich JD, et al. N Engl J Med 2014; 370(20):

16 From: Prevention of Hepatitis C by Screening and Treatment in U.S. Prisons Ann Intern Med. Published online November 24, doi: /m Date of download: 11/24/2015 Copyright American College of Physicians. All rights reserved.

17 Confirmation Data 1/3 rd patients who screen positive fail to receive confirmation testing Rates best in continuity clinics

18 HCV Can Be Eliminated No non-human reservoir Simple and accurate diagnostic tools Transmission can be prevented Infection can be cleared from host Highly effective, safe drugs exists given for a finite period of time

19 HCV Projected To Be A Rare Disease By 2036 Estimated HCV prevalence in the US from Our study underscores the need for more aggressive screening strategies to reduce the burden of HCV infection. Screening strategies that work today may not work tomorrow Ann Intern Med. 2014;161:

20 # Screened for one Positive Newly Dx It will be more difficult to diagnose new cases as diagnosis rate increases and prevalence decreases 10,000 1, US General Population US Baby Boomers 1 0% 1% 2% 3% 4% 5% 6% 7% 8% 9% 10% HCV Prevalence Focused screening strategies will allow for more efficient diagnosis of HCV infected patients Wedemeyer H, Duberg AS, Buti M, Rosenberg WM, Frankova S, Esmat G, et al. Strategies to manage hepatitis C virus (HCV) disease burden. J Viral Hepat 2014;21 Suppl 1:

21 The Reality In contrast to vaccination, curative efforts require identification HCV concentrates in marginalized groups Restriction on therapy will prevent elimination

22 Total Individuals (000) US HCV infected population (Individuals in 000s) 3,500 3,200 3,000 2,500 2,000 1,500 PWID, Homeless, Immigrants, Incarcerated, & Veterans 1,600 1, % 4% Viremic HCV Infections Diagnosed Treated 63 Prevalence: Denniston MM, Jiles RB, Drobeniuc J, Klevens RM, Ward JW, McQuillan GM, Holmberg SD. Ann Intern Med 2014 March 4;160(5): Chak E, Talal A, Sherman KE, Schiff E, Saab S. Liver Int 2011;31(8): Diagnosed: Denniston MM, Klevens RM, McQuillan GM, Jiles RB. Hepatology 2012 June;55(6): Treated: Razavi H, Elkhoury AC, Elbasha E, Estes C, Pasini K, Poynard T, Kumar R. Hepatology 2013 June;57(6):

23 Identifying Priorities to Improve Outcomes 100% HCV Care Cascade Unaware of diagnosis 50% 32 38% 20 23% 12 18% 7 11% 5 6% Holmberg SD, et al. N Engl J Med. 2013:368(20):

24 Barriers to HCV Treatment Factors related to receiving HCV treatment High education level of the patients (P = 0.004) Advanced fibrosis (P < 0.001) Care at a Center of Excellence (P = 0.009) Liver Int Feb;35(2):401-8.

25 Why Not Treat? Adherence Contraindications Undervalued Access

26 Factors Associated with Nonadherence Hypertension, Dyslipidemia, Type 2 diabetes Young age Low self-efficacy Perceptions of their illness Economic Perceived barriers to taking medicines High depressive symptoms Negative expectations NOT low socioeconomic status Value Health Mar;18(2): Patient Prefer Adherence Feb 20;9: Value Health Mar;17(2):288-96

27 Issues More Specific to HCV: Treating People Who Inject Drugs (PWID) Undertreated No impact on treatment completion: History of IDU Recent use Occasional use during treatment Frequent use associated with lower SVR and adherence Treatment as prevention: PWIDs majority of new infections Secondary transmission Clin Infect Dis. 2009;49: ; Clin Infect Dis. 2013;57(suppl 2):S129-S137; Clin Infect Dis Aug; 57 Suppl 2():S32-8.

28 Patient Buy-in Most Important Patient motivation is the most important factor in medical adherence ~25% of adults have <90% adherence to ART Demographic factors do not predict suboptimal adherence Motivational interviewing and printed adherence information do not improve adherence Pladevall Diabetes Educ Dec 8. J Manag Care Pharm Jan;20(1):86-92.

29 Why not treat? Adherence Contraindications Traditional rules may persist but no long apply Undervalued Access

30 Effectiveness of HCV Therapy Have Been Reduced by Eligibility Restrictions, Initiation, and Adherence Results of a comprehensive literature review on the course of HCV treatment in clinical care settings North CS, et al. Gen Hosp Psych. 35 (2013)

31 Factors Associated with Not Receiving Treatment 17% (5,533/32,283) were treated 42% interferon ineligible or intolerant 50% had a significant comorbid illness Factors Associated with NOT Receiving Treatment Independent variables Odds Ratio P-value Anemia < Autoimmune disorder Renal dysfunction Cardiovascular disease < Psychosis/Bipolar Severe lung disease < Substance abuse < MELD ( 12) < Nyberg LM, EASL, 2014, O67

32 Adherence Contraindications Undervalued Physicians Patients Payers Access Why not treat? SVR =CURE

33 Treatment with LDV/SOF Improves Patient Reported Outcomes: Results from the ION 1, 2, and 3 clinical trials Post SVR12 improvements in PRO scores Hepatology 18 MAR 2015 DOI: /hep

34 Antiviral treatment for HCV Improves Renal and Cardiovascular Outcomes in Diabetic Patients HCV: 2-3 odds of DM IR and DM increase risk and rate of fibrosis SVR may prevent and improve IR Brandman et al. Diabetes Care May;35(5): Aghemo A et al.. Hepatology.2012;56(5): Hepatology Volume 59, Issue 4, pages , 18 FEB 2014 DOI: /hep

35 Long Term Benefit of SVR Lower risk of HCC Lower risk of cirrhosis Lower risk of decompensation Lower risk of transplant Lower all-cause Mortality

36 All-cause mortality, % Liver-related mortality or liver transplantation, % SVR is Associated with Reduced All-Cause Mortality Among HCV-infected Persons 530 adults in Europe prospectively followed for median 8.4 years after HCV treatment 192 (36%) achieved SVR P<0.001 All-cause mortality Liver-related mortality or liver transplantation P< Without SVR Time, y With SVR No. at risk Without SVR With SVR Without SVR Time, y With SVR No. at risk Without SVR With SVR Van der Meer, et al. JAMA 2012:308:

37 Why not treat? Adherence Contraindications Undervalued Access Providers Treatment

38 Elimination of HCV Can Be Accomplished With Modest Increase in Treatment and SVR Treatment PI/P/R in G1 and P/R in G2/3 DAA/P/R in G1/3, DAA/R in G2 Oral DAAs Oral DAAs Oral DAAs SVR G1 60% 80% 90% 95% 95% SVR G2 80% 85% 90% 95% 95% SVR G3 65% 70% 90% 95% 95% Treated 60,000 90,000 90, , ,750 Newly Dxed 110, , , , ,000 Treated Segment F2 F3 F2 F2 F1 Dxed Diagnosed G1 Genotype 1 P PegIFN R ribavirin It is important to note that we don t need to start treating everyone to achieve elimination by 2030 H. Razavi. CDA August 1 st,

39 Peak Treatment 35% Higher Than Peak Treatment in ,000 Number of Treated Patients in the US 120, ,000 80,000 60,000 40,000 20,000 0 CDA analysis of IMS PegIFN sales data Today 4 patients can be treated in the same period of time as 1 in 2005 H. Razavi. CDA August 1 st,

40 All-oral HCV Treatment is Cost-Effective Study Leidner, Hepatology 2015 Rein, CID 2015 Najafzadeh, Ann Int Med 2015 Chhatwal, Ann Int Med 2015 Key Finding For 55 yo treated with $100,000 regimen and SVR 90%, treating F2 compared to waiting until F3 had CE= $37,300/QALY. Threshold cost for treating at F0 versus waiting until F1 to yield $50,000/QALY = $22,200 LDV/SOF and 3D compared to no treatment yields $32,000 - $35,000/QALY. Compared to no treatment, the threshold cost for treating F0 with an all-oral regimen = $47,000/QALY Compared to no treatment in Geno-1, costs per additional QALY gained for LDV/SOF = $25,291 and PEG/RBV = $24,833 If LDV/SOF <$66,000/treatment course, would be cost saving Average ICER for SOF-based treatment compared to prior SOC = $55,378/QALY. Range = $9,703/QALY for naïve, cirrhotic G-1 to $410,548/QALY for treatment-experienced G-3 without cirrhosis Adapted from: Pricing of Drugs and Formulary Placement: Making Sense of Hepatitis C Treatment Camilla S. Graham, MD, MPH.

41 Budget Impact Is HCV Therapy Cost Prohibitive? 61 $136 billion Total spending on SOF/LDV to treat all US HCV-infected patients in the next 5 years Cost-effective Especially for Medicaid, Medicare and VA Better value for money Advanced disease, Female, younger, PWID ICERs within range of therapies for other medical conditions in the US Resources needed immense and unsustainable Fix is not as simple as expanding the provider pool. Access to simple, effective therapy will expand the number of willing treaters. Ann Intern Med. 2015;162(6): doi: /m

42 State Responses to High Demand State Medicaid programs and/or managed care plans utilization management of medications Concern for cost led states to implement restrictive access requirements Three categories of restrictions: Restrictions based on substance use or abuse Restrictions based on disease progression/fibrosis Restrictions based on prescriber limitations (i.e., who can treat people with HCV) Difficulty in side effect management replaced by difficulty in getting drug approval (Malinda Ellwood: Center for Health Law and Policy Innovation of Harvard Law School)

43 Patient with minimal liver disease are denied access to HCV treatment in many settings Medicaid reimbursement criteria for sofosbuvir based on documented liver fibrosis stage required for reimbursement Barua et al. Ann Intern Med 2015

44 HCV cure is associated with improved survival in patients with F0/F1 disease after 15 years Patients were selected from a single-center cohort of 4293 consecutive patients since 1992 Progression to F3/F4 was observed in 15.3% of F0/F1 patients Jezequel et al. Journal of Hepatology 2015 (EASL meeting)

45 From: Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population JAMA Intern Med. Published online November 23, doi: /jamainternmed Date of download: 11/24/2015 Copyright 2015 American Medical Association. All rights reserved.

46 Patients using drugs and alcohol are denied access to HCV treatment in some settings Barua et al. Ann Intern Med 2015

47 Alcohol-related conditions are associated with increased risk of HCV-related death Ly et al. Annals Intern Med 2012

48 Effectiveness of HCV Therapy is Reduced by Eligibility Restrictions, Initiation, and Adherence Results of a comprehensive literature review on the course of HCV treatment in clinical care settings North CS, et al. Gen Hosp Psych. 35 (2013)

49 Identifying Priorities to Improve Outcomes 100% HCV Care Cascade Reinfection Long term Monitoring Unaware of diagnosis 50% 32 38% 20 23% 12 18% 7 11% 5 6% Holmberg SD, et al. N Engl J Med. 2013:368(20):

50 Fig. 1 SVR Decreases But Does Not Eliminate Incidence of Hepatocellular Carcinoma Nagaoki et al., AASLD 2014; #1977 Source: Journal of Hepatology 2010; 52: (DOI: /j.jhep )

51 Conclusions HCV elimination can only be achieved with screening and linkage to care strategies Elimination of HCV prior to 2030 in the US is achievable with only modest increases in treatment Prioritization may be necessary initially but can not be long term strategy Finding undiagnosed HCV will become increasingly difficult as overall HCV prevalence declines A coordinated effort including primary care education, creative efforts at screening at-risk populations, policy and federal support will be essential to minimize HCV related health care burden

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