session 2: finding the missing millions...

Session 2: Finding the missing

millions – HCV

Best practice talk - France

Sylvie Deuffic-Burban

Inserm IAME U1137, Paris, France

Fight against viral hepatitis in France

International Viral Hepatitis Elimination Meeting (IVHEM) - Amsterdam - December 7-8, 2018

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Results of the 1st national seroprevalence survey conducted in 1994 among nearly 6,300 volunteers1.05% (95% CI, 0.75-1.34) = 500,000-650,000 individualsAmong them, only 24% aware of their infection Dubois et al, Hepatology 1997



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Results of the 1st national seroprevalence survey conducted in

19941.05% (95% CI, 0.75-1.34) = 500,000-650,000 individuals

Among them, only 24% aware of their infection

First national plan has been developed involving 6 programs:Prevention of new infections, enforcement of screening access, improvement of care management, implementation of a surveillance system, clinical research, and evaluation



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ANRS-Coquelicot study, in particular to

assess the prevalence of HCV infections

and its risk factors

2nd national seroprevalence survey in

the general population, to obtain new

national and regional prevalence

estimates

2007: results of the 2nd national seroprevalence survey in general populationAnti-HVC prevalence = 0.84% (95%CI, 0.65-1.10) = 367,055 individuals0.53% chronically infected (95%CI, 0.40-0.70) = 221,386 individuals

Among them 57% aware of their status in 20041 (vs. 24% in 1994)2

1Dubois et al, Hepatology 1997; 2Meffre et al, J Med Virol 2010



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3rd national program against hepatitis B and C (2009-2012)Need to improve the prevention and detection of more precarious and more exposed populations to hepatitis B and C, to improve the practice of screening and to reorient patient care arrangements to the liberal sector

• Independent evaluation and annual

reports

• Annual recommendations

meetings (French association for

the study of the liver, AFEF)



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HEPATHER cohort

2012

2012: Constitution of a national cohort, HEPATHER (nearly 21,000 patients, HBV or HCV)To improve management and care, giving the changing era of therapeutic optionsTo analyze the long term effects of therapy, to identify psychological and behavioral correlates of access to care, to evaluate the cost-effectiveness of HBV and HCV treatments and quality of life…

http://www.anrs.fr/sites/default/files/2018-09/presentation_cohorte_anrs_hepather.pdf


reports






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HEPATHER cohort

2012


reports




2014 2016

1st general

report on viral

hepatitis

(HBV+HCV)

2nd report

on viral

hepatitis

1Management of persons with hepatitis B or hepatitis C virus infection. Report of recommendations 2014. Coordinated by Pr Daniel Dhumeaux for

the ANRS and AFEF. 2Prise en charge thérapeutique et suivi de l’ensemble des personnes infectées par le virus de l’hépatite C. Rapport de

recommandations 2016. Sous la direction du Pr Daniel Dhumeaux. Sous l’égide de l’ANRS et du CNS et avec le concours de l’AFEF.

Favorable therapeutic

context in 2013

Therapeutic progress accompanied by an increase in health related costs

Concern raised about the high cost new DAAS

How best to utilize the resources that are available?


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0

1000

2000

3000

4000

5000

Peg-Riba Telaprevir Boceprevir Sofosbuvir

unit price €/week

First cost-effectiveness

evaluation of HCV DAAs in

France

12w=57,000€*

*price in early access (Temporary Authorization of Use)

Cost-effectiveness analysis of

(1) IFN-based new DAAs vs. TVR/BOC

triple therapy,

(2) IFN-based new DAAs initiation

strategies given the close

availability of IFN-free regimens


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Deuffic-Burban et al, J Hepatol 2014


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Strategies; patients F0-1 Lifetime cost(€)

Life expectancy(yrs)

QALY (yrs) ICER (€/QALY)

Treat with TVR/BOC-based triple therapywhen ≥ F2

25,700 20.80 19.32

Treat with IFN-based new DAAs* when ≥ F2 40,500 21.10 19.71 37,900

Treat with IFN-based new DAAs* regardlessof fibrosis

64,300 21.13 19.94 103,500

Await IFN-free regimens** (2015); thentreat when ≥ F2

69,100 21.22 19.84 Dominated

Await IFN-free regimens** (2015); thentreat regardless of fibrosis

112,500 21.25 20.09 321,300

*€60,000 for 12 weeks based on expanded access cost for sofosbuvir in France; **assumed 2 times more expensive



triple therapy,





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Strategies; patients F0-1 Lifetime cost(€)

Life expectancy(yrs)

QALY (yrs) ICER (€/QALY)

Treat with TVR/BOC-based triple therapywhen ≥ F2

25,700 20.80 19.32

Treat with IFN-based new DAAs* when ≥ F2 40,500 21.10 19.71 37,900

Treat with IFN-based new DAAs* regardlessof fibrosis

64,300 21.13 19.94 103,500

Await IFN-free regimens** (2015); thentreat when ≥ F2

69,100 21.22 19.84 Dominated

Await IFN-free regimens** (2015); thentreat regardless of fibrosis

112,500 21.25 20.09 321,300

*€60,000 for 12 weeks based on expanded access cost for sofosbuvir in France; **assumed 2 times more expensive



triple therapy,




Treating patients with fibrosis ≥ F2 with IFN-based new DAAs was both

effective and cost-effective compared to TVR/BOC triple therapy

Treating with IFN-based new DAAs regardless of fibrosis is an even more

efficient strategy but required lower price to be cost-effective


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41,000€ for 12 weeks vs. 57,000€ in early access

programs (Temporary Authorization of Use)

Restriction to F3-F4 and severe F2

New evaluation…

Long-term evaluation

Short-term evaluation

Budget impact of treating all HCV-infected inviduals

€ 3.5 to € 7.2 billion over 5 years


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Deuffic-Burban et al, J Viral Hepat 2016

8100 21300 19400 920040400

395000

264500

23000

0

50000

100000

150000

200000

250000

300000

350000

400000

450000

GT1 GT2 GT3 GT4

ICER

(€ p

er

QA

LY)

IFN-based new DAAs regadless of fibrosis

IFN-free new DAAs regadless of fibrosis

± IFN

New evaluation…

Long-term evaluation

Short-term evaluation

Budget impact of treating all HCV-infected inviduals

€ 3.5 to € 7.2 billion over 5 years


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Deuffic-Burban et al, J Viral Hepat 2016

8100 21300 19400 920040400

395000

264500

23000

0

50000

100000

150000

200000

250000

300000

350000

400000

450000

GT1 GT2 GT3 GT4

ICER

(€ p

er

QA

LY)

IFN-based new DAAs regadless of fibrosis

IFN-free new DAAs regadless of fibrosis

± IFN

Significant impact on the health budget to treat everyone

= € 3.5 to € 7.2 billion over 5 years

Unless a significant decrease of costs


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Universal treatment access

Lower and unique price

= 28,700€

A new challenge: towards universal

screening?

HCV screening still targets people at high risk of infection

Several reasons for extending screening

>10% diagnosed at an advanced stage of HCV disease

High effective and well tolerated treatments

Availability of rapid screening tests

Strategies evaluated compared to risk-based screening (S1)

S2 = S1 + all men aged 18 to 59 years

S3 = S1 + all adults aged 40 to 59

S4 = S1 + all adults aged 40 to 80

S5 = all adults 18-80


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A new challenge: towards universal

screening?

Assuming treatment initiation regardless of fibrosis and immediately after diagnosis, at 28,700€ the cure

Targeting all adults 40-80

had the lowest cost-

effectiveness ratio

Universal screening was

even more effective and

was cost-effective


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Towards viral elimination in France: last

recommendations (AFEF)

The most recent recommendations from the French association for the study of the liver (AFEF) call for extending HCV screening to all adults

Screening every adult at least once in their life, either by viral serology through

standard blood sampling, or by rapid screening tests

HBV, HCV and HIV screening must be combined

All screening tests must be reimbursed 100%

But, to date, the Haute Authorité de la Santé has not changed its recommendations for hepatitis C screening but is currently considering experts’ recommendations and our study in light of future recommendations


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Towards viral elimination in France: last

recommendations (AFEF)

Universal treatment through two complementary care paths: simplified / specialized


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• HCV treatment prescription

by all physicians

• Treatment monitoring

performed by non-medical

caregivers

• DAAs available in all

pharmacies

Flagship of government plan

“prevention priority”

Bring care closer to the most exposed people, and strengthen screening

Reconsider the model of specialized hospital therapeutic management to bring

prevention, screening, treatment and follow-up closer to the people

Promote proximity screening with rapid screening tests

Continue the work of local centers such as “care, support and prevention

centers in addiction” (CSAPA) and “reception and support centers for reducing

the risks of drug users” (CAARUD)


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Strong action for the elimination of hepatitis C by 2025

Evolution of the French cascade of care


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0

50000

100000

150000

200000

250000

ARN-VHC+ Diagnosed Treated Cured

2004 2014 2017

Meffre et al, J Med Virol 2010; Brouard et al, PLoS One 2015; Deuffic-Burban, personal communication

Conclusion

Set up a national seroprevalence survey to assess the national HCV burden and assist with the development of a national plan

Develop a comprehensive elimination plan that addresses

Surveillance (including provider training),

Prevention (e.g., infection control, blood safety, and harm reduction),

Testing (including public awareness campaigns and improving implementation

of screening activities),

Linkage to care and treatment access

Develop mathematical models to evaluate public health strategies


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Team DeSCID (Decision Sciences in Infectious Disease

Prevention, Control and Care), Inserm-IAME

Service Maladie de l’Appareil Digestif, Hôpital Huriez,

CHRU Lille & Inserm-LIRIC, Lille


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UMR 995

session 2: finding the missing millions...

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