Eliminating HCV: Models of Reducing the Burden

Transcription

1 Eliminating HCV: Models of Reducing the Burden Arthur Y. Kim, MD Massachusetts General Hospital Harvard Medical School National Strategy for Elimination of HCV Institutes of Medicine, Washington DC December 16, 2015

2 Disclosure Statement for Arthur Kim Grant/research support to institution: Gilead Consultant/Scientific Advisory Board: None (last 12 months, updated 12/9/15) I will discuss the following off-label use in this presentation: Antiviral agents for acute HCV infection Funding: National Institutes of Health (National Institute of Allergy and Infectious Diseases, National Institute of Drug Abuse)

3 Key questions / outline Elimination of Hepatitis C Is elimination possible? Cost Effectiveness & Burden of Hepatitis C Is screening for HCV cost-effective? Is treatment for HCV cost-effective? What is the cost burden of HCV elimination? Barriers to HCV Eradiction Reality check in Massachusetts What are knowledge gaps?

4 Definitions Eradication: permanent reduction to zero of worldwide incidence of infection Example: Smallpox Elimination: reduction to zero of incidence of disease or infection in a defined geographical area, requiring presence of continued control measures Examples: measles, polio Control: reduction in the incidence, prevalence, morbidity or mortality of an infectious disease to acceptable level Greg Dore, HCV Treatment as Prevention, CROI 2015

5 Incidence, prevalence and sustaining an epidemic

6 HCV prevalence in the interferon era Declining incidence Asymptomatic infection Unknown serostatus Improved screening Side effects of treatment; poor uptake Better therapies Better access

7 What can we learn from models? 1. Individual-level outcomes simulates natural history - population effects 2. Modulate effects of single or multiple potential interventions 3. Timelines longer than cohort studies 4. Can associate costs, quality of life Figure: Kabiri et al. Annals of Internal Medicine 2014

8 What is cost-effectiveness? Cost-effectiveness: quantifies the value of treatment seeks to maximize impact seeks to improve public health by maximizing population-level benefits does NOT seek to minimize cost Major measure: cost-effectiveness ratio (ICER): Additional Resources Use ($) Additional Health Benefits (QALY) Adapted from Ben Linas, IAS-USA

9 What are ICERs that we are willing to pay? $/QALY* ART for HIV infection 1 $31,500 Statins for primary prevention 2 $47,700 Implantable defibrillators 3 $81,900 Dialysis, seriously ill adults 4 $187,000 * Converted to 2015 currency year 1 Freedberg et al. NEJM 2 Pletcher et al. Annals Internal Medicine Sanders et al. NEJM Hamel et al. Annals Internal Medicine 1997 Adapted from Ben Linas, IAS-USA

10 Is screening for HCV cost-effective and what is the burden of disease averted? Birth cohort screening 1st generation PI era (ICER $35,700-37,700/QALY) 1,2 Screening in high-risk populations HIV+MSM (ICER $57,800/QALY for yearly antibody) 3 Screening in high prevalence settings Prison setting (ICER $19,600-29,200/QALY) 4 1 Rein DB, Ann Intern Med McGarry LJ, et al. Hepatology Linas et al. Clinical Infectious Diseases 4 He et al. Ann Intern Med 2015

11 Is treatment cost-effective? Stratified by cirrhosis status & genotype Genotype 1 Range of ICERs Non-cirrhotic $31,000 - $70,000 Cirrhotic $9,700 - $79,000 Genotype 2 Range of ICERs Non-cirrhotic $34,000 - $238,000 Cirrhotic $27,000 - $281,000 Genotype 3 Range of ICERs Non-cirrhotic $51,000 - >$500,000 Cirrhotic $51,000 - $383,000 Courtesy Ben Linas Linas et al. Ann Intern Med 2015 Najafzadeh et al. Ann Intern Med 2015 Chhatwal et al. Ann Intern Med 2015 Rein et al. Clin Infect Dis 2015 Leidner et al. Hepatology 2015

12 For patients immediately treated at F0 (versus delaying treatment until F1), the threshold of trea

13 Cases Averted With Birth Cohort HCV Testing versus Risk-Based HCV Testing (1st gen PI era) McGarry LJ, et al. Hepatology. 2012;55:

14 Cost of reducing HCV burden Disease progression HCV disease characteris.c s Pa.ent demographics What we evaluated? Therapeu.c advances Screening policies Hepa..s C Simula.on Core Changing HCV prevalence Number of people seeking treatment with oral DAAs Cost of HCV treatment Cost associated with advanced HCV outcomes, e.g. hepatocellular carcinoma, liver transplanta?on. Affordable Care Act Insurance + Access Cost Kabiri M et al. Annals of Internal Medicine 2014;161: Slide provided by J. Chhatwal

15 Cost of reducing HCV burden Launch of 1 st gen PIs Launch oral DAAs + Affordable Care Act + Screening updates Compe??on brings down drug costs $17 billion Majority of exis?ng pa?ents treated $2 billion \ Availability of generics Chhatwal et al. AASLD 2015 Abstract 151

16 Cost savings from lower rates of decompensated cirrhosis Chhatwal et al. AASLD 2015 Abstract 151

17 HCV-Associated Disease Burden ( ) Disease Burden ( ) 800, , , , No Treatment Pre- DAA Era DAA Era Liver- related Death HCC Decomp. Cirrhosis Liver Transplants Chhatwal et al. AASLD 2015 Abstract % reduc.on in HCV- associated disease burden

18 The Cost of Making HCV a Rare Disease Comparison of HCV and HIV Spending $106 billion $144 billion It would cost $106 billion to make HCV a rare disease in the next 25 years. In comparison, spending on HIV/AIDS in the last 5 years ( ) was $144 billion. Chhatwal et al. AASLD 2015 Abstract 151

19 Screening and Treatment in Prisons Prevents ~1270 cases / year Incidence calibrated to estimated 17,900/year baseline Assumptions include knowledge of serostatus reduces transmission 50%; probability of transmission HR 12 if sharing needles, risk He et al. Ann Intern Med 2015

20 Model of HCV infection among PWID (Martin et al. CID 2013)

21 Can treatment as prevention be applied for HCV among people who inject drugs (PWID)? Modeling DAAs 125! # treatments to achieve prevalence reduction per 1000 PWID! 100! 75! 50! 25! 0! 8! 15! 1/4 prevalence reduction! 1/2 prevalence reduction! 3/4 prevalence reduction! 22! 22! 40! 54! 45! 76! Edinburgh! Melbourne! Vancouver! 98! Martin et al. Hepatology % baseline prevalence 50% prevalence 65% prevalence

22 Reinfection rates among PWID in the interferon era Incidence ranges significantly (0-33%)? selection: provider/patient both willing to use IFN Only one data source from the U.S.

23 R0 (basic reproductive number) R0 = C * P * D C = # of contacts per unit of time P = probability of transmission per contact with infectious person D = duration that patient is infectious to others

24 R0 (basic reproductive number) R0 = C * P * D C = # of contacts per unit of time Smaller or limited networks may decrease C P = probability of transmission per contact with infectious person Clean injection equipment may decrease P D = duration that patient is infectious to others Behaviors that affect C and/or P amongst PWID cycle over time / locale. Knowledge of infectious status may affect behaviors. Ultimately, duration of infectiousness is a major barrier as most infected persons remain infectious without treatment.

25 Concepts of immunity in a population reducing incidence Rationale to reduce risk to susceptible individuals with clean injecting equipment, vaccine

26 Combination of DAA treatment & Opiate Substitution and High-coverage Needle/Syringe Exchange (HCNSE) DAAs needed to reduce prevalence by 50% over Martin et al. CID 2013

27 Driving forces behind models that show screening and treatment are cost-effective 1. Drug cost Example: GT3, lower efficacy of prolonged (more expensive) treatment More attractive with fixed-dose combinations for GT3 Screening test costs are trumped by drug costs 2. Fibrosis stage (cirrhosis versus not) 3. Linkage and access assumptions 4. Benefits of SVR (gain in QALYs) 5. Quality of life assumptions for low fibrosis patients HCV screening and therapy achieves acceptable incremental costeffective ratios (with some exceptions) but the overall cost burden is high

28 Limitations of these models 1. While science of modeling cost-effectiveness and burden reduction may support screening and treatment, societal perspective not convincing or accepted by stakeholders 2.Drug costs are usually assumed to be wholesale acquisition costs True costs generally lower 3. Inputs are based on data sources that themselves make extrapolations or assumptions and/or do not include certain populations Homeless, incarcerated Novel epidemics (PWID, HIV)

29 Real world data that confirm, inform or alter model-based projections Prevalence Baby boomer screening Incidence (mostly PWID / HIV MSM) Primary infection rates Re-infection rates (post-treatment) Effects of interventions Screening availability Linkage and access to care Real-world SVR treatment (eg TRIO, TARGET)

30 Incidence among PWID differs in Amsterdam versus two sites in U.S. Amsterdam Baltimore Incidence (per 100 py) San Francisco Morris M et al. Manuscript in preparation

31 Past year initiation of heroin among individuals aged 12 or older, by age group: 2002 to 2013 Source: SAMHSA, CBHSQ, National Surveys on Drug Use and Health (NSDUHs), 2002 to 2005, 2006 to 2010 (revised March 2012), and 2011 to 2013.

32 Massachusetts state reporting of HCV HCV Ab (+) HCV RNA (+) Real-time electronic reporting Provider Case report form Laboratory Applies CDC definition Reports to CDC MAVEN Integrated surveillance State Board of Health

33 HCV Surveillance in Massachusetts In 2002, data suggest a peak age in late 40s of HCV cases In recent years, there are ~2000 prevalent cases / yr of HCV annually aged 15-29, all of whom must have had ahcv in past Source: Onofrey et al MMWR: May 6, 2011 / 60(17);

34 Number discrepancies, even before widespread baby-boomer screening , ,000 0 Estimated HCV cases in MA, NHANES Actual HCV cases, MA Slide courtesy: Dan Church, MA DPH

35 Reported confirmed and probable cases of HCV infection in MA, Slide courtesy: Dan Church, MA DPH

36 The burden of HCV is an iceberg Only the tip is visible Cases not reported or classified (incomplete surveillance) Cases not recognized (incomplete diagnosis) Increasing population at risk Fragmented care of high-risk-groups High-risk groups that don t present to care 49

37 Toolbox for HCV prevention for PWID HCV testing and counseling Drug treatment Reducing transmission from positive partners Vaccine Change injecting behavior Clean injecting equipment Syringes/needles extras Safe injecting locations Viral titer testing Antiviral treatment Adapted from Kim Page, UNM

38 Incidence, prevalence and sustaining an epidemic Rising opiate use Lack of prevention services Asymptomatic infection Unknown serostatus Access restrictions and cost of treatment

39 Conclusions Models suggest elimination is a large scale commitment but would eventually be worth it from societal perspective Elimination is possible even accounting for reinfection in high risk groups Models are reliant on sources but there are data gaps: What is the burden? Appears high in Massachusetts Differences regionally and internationally Novel epidemics (rural/suburban opioids) Networks of transmission Understanding of immunology could early treatment preserve immune responses? Understanding factors leading to reinfection

40 Acknowledgements Massachusetts DPH Dan Church Shauna Onofrey Al DeMaria Gillian Haney Boston Medical Center Alex Walley Benjamin Linas Tufts Barbara Mcgovern John Wong Harvard Medical School Jagpreet Chhatwal (MGH) Camille Graham (BIDMC) Georg Lauer (MGH) James Morrill (MGH) CDC John Ward Montefiore Alain Litwin UCSD Natasha Martin Davey Smith University of New Mexico Kim Page Kirby Institute /University of New South Wales, Sydney Greg Dore University of Amsterdam Maria Prins Johns Hopkins Andrea Cox David Thomas UCSF Meghan Morris