Treatment Outcomes for Chronic Hepatitis C Infection with Direct Acting Antivirals among Inmates in Federal Corrections

Smith JM, Boudreau H, Kom E, Tremblay T

Health Services, Correctional Services Canada

Disclosure

I am a federal public servant employed at the Correctional Service Canada. My responsibilities include the epidemiological analysis of treatment data and providing advice on policy and programs to senior management.

I have no actual or potential conflict of interest in relation to this topic or presentation.

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1. Overview of CSC

2. HCV Epidemiology in CSC

3. CSC Formulary

4. HCV Treatment - Results

5. Summary

Presentation Outline

• Offenders sentenced to 2 years or more are sent to a federal institution to serve their sentence

• Under CCRA, CSC provides all essential health care and access to non-essential mental health services that conforms to professionally accepted standards.

• In fiscal year 2014-2015:– There were 4,871 new warrants of committal issued

– 15,043 incarcerated offenders on any given day

– Total “flow through” of 22,958 inmates

– 80% of offenders had a sentence length of 2-5 years

(Source: CSC Report on Plans and Priorities 2015-16)

(Source: Corporate Reporting System, Inmate Movement and Admissions Models, April 2016)

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1: Overview of CSCCorrections and Conditional Release Act

1: Overview of CSCCSC Regions

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(Moncton)

2: HCV Epidemiology in CSCHIV and HCV Testing on Admission

6Preliminary Unpublished Data, CSC 2014

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

HIV 37.1% 41.2% 55.7% 48.6% 47.9% 50.2% 52.1% 50.6% 59.4% 55.2% 64.5% 78.1% 88.5% 78.6%

HCV 36.8% 44.5% 55.5% 46.9% 47.0% 49.1% 49.4% 49.6% 58.9% 53.5% 62.2% 71.0% 89.9% 79.6%

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

PE

RC

EN

T

2: HCV Epidemiology in CSCNewly Diagnosed HCV on Admission

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2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

NEWLY Dx HCV 244 195 226 220 254 178 193 113 140 137 113 138 134 177

Diagnostic Yield 154 102 98 111 122 75 77 47 49 50 34 39 35 37

0

20

40

60

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100

120

140

160

180

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Dia

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New

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In

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ns

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

FEMALE 42.4% 41.2% 38.6% 37.0% 37.6% 39.5% 36.0% 42.1% 34.9% 31.8% 32.1% 33.5% 24.2% 24.6%

MALE 19.7% 23.2% 25.5% 26.5% 24.8% 29.0% 27.3% 32.3% 30.0% 24.7% 23.7% 21.6% 18.6% 17.8%

TOTAL 20.1% 23.6% 25.8% 26.8% 25.2% 29.3% 27.6% 32.7% 30.2% 25.0% 24.0% 22.1% 18.8% 18.1%

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

35.0%

40.0%

45.0%

Ye

ar-

en

d P

reva

len

ce

Year-end HCV Prevalence among Inmates in CSC 2000-2013 by Gender

FEMALE MALE TOTAL

2: HCV Epidemiology in CSCYear-end HCV Prevalence by Gender

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All oral DAA Therapy

Introduced(e.g. Harvoni)

2010-2011 2011-2012 2012-2013 2013-2014 2014-2015 2015-2016

# Initiated 178 246 258 241 142 305

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350

400

Nu

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Inm

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Year

2: HCV Epidemiology in CSCHCV Treatment Initiation

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1st Gen Triple Therapy

Introduced(e.g. boceprevir +

peginterferon + ribavirin)

3: CSC FormularyHCV Treatment and Medications

• Inmates with Hepatitis C infection are referred to an infectious disease specialist for consultation about treatment. Treatment for Hepatitis C is voluntary and managed by the medical specialist.

• CSC National Formulary criteria are based on recommendations from the Common Drug Review (CDR) of the Canadian Agency for Drugs and Technologies in Health (CADTH) and the CSC National Pharmacy and Therapeutics (NP&T) Committee.

• CSC listed the new all-oral Hepatitis C therapies on the CSC National Formulary:– Sovaldi (January 2015)– Harvoni (March 2015)– Holkira Pak (September 2015)

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3: CSC FormularyHCV Treatment and Medications

• CSC criteria originally aligned with CDR recommendations on fibrosis (F2-F4)

• In August 2015 CSC adopted a strategy of prioritizing treatments to fibrosis F3-F4 (those with highest severity)

• A review process is in place to consider lower levels of fibrosis on an exceptional case-by-case basis (i.e., F2 with extrahepatic complications)

• This approach was not unique to CSC. The U.S. Federal Bureau of Prisons adopted a similar strategy

• As of April 1 2016 the prioritization has been lifted, criteria revert to F2-F4

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4: HCV Treatment - ResultsMethods

Inmates initiated on HCV treatment are tracked in an electronic database. Information collected includes:

– Genotype

– Fibrosis

– Treatment History

– Treatment regimen / duration

– Treatment status (discontinued, released on treatment, completed)

– HCV RNA (end of treatment, 12 / 24 weeks post treatment)

– Treatment outcome (treatment failure, relapse, sustained viral response)

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4: HCV Treatment - Results Methods

• Information from the treatment registry were extracted for analysis on April 5th 2016

– Includes initiations from February 1st 2015 to April 5, 2016

– Inmates with Genotype 1 (G1) on PI (boceprevir, telaprevir, or simeprevir) were excluded

– Inmates on dual therapy (peginterferon + ribavirin) were excluded

• Descriptive demographic data

• Treatment status and outcome were analyzed by genotype

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4: HCV Treatment - Results Demographics

• N=312 records were extracted for analysis

– Average age: 49 years (min: 25 max: 74)

– Female: 4.4%

– Aboriginal: 28.4%

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4: HCV Treatment - Results Treatment History

Of the 312 treatment initiations

• Treatment History available for n=275 (88%)

– 181 (66%) were treatment naïve

– 94 (34%) were re-treatments • 49 null responders

• 9 partial responders

• 36 relapsers

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4: HCV Treatment - Results Genotype

Genotype Frequency Proportion

G1 260 83%

G2 9 3%

G3 42 13%

G4 1 <1%

TOTAL 312

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G1 includes coinfected patients (n=4)

4: HCV Results: G1 (n=261)Treatment Regimen by Fibrosis

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Fibrosis

Number of Treatment Starts*

Harvoni Sovaldi HolkiraPak

Total

F0 0 0 0 0

F1 2 1 0 3

F2 32 5 0 37

F3 84 5 5 94

F4 113 7 5 125

Total 233** 18 10 261**

N=312*Includes G1 co-infected (n=4) and G4 (n=1)** Includes missing fibrosis (n=2)

4: HCV Results: G1 (n=261)Treatment Outcome by Regimen

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Outcome Harvoni Sovaldi

Initiated 233 18

Still On Treatment 44 1

Treatment Ended 189 17

Released on Treatment 6 2

Discontinued 5 1

Completed 178 (94%) 14 (82%)

SVR Achieved 107 (96%) 6 (86%)

SVR Not Achieved 4 1

SVR N/A 67 7

N=312Holkira Pak (n=10) not shown as starts are too recent (no completions)

4: HCV Results: G1 on Harvoni (n=233)Treatment Outcome by Treatment History

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Outcome

Tx Naive Tx Experienced

8 weeks 12 weeks 12 weeks +RBV

24 weeks

Initiated 44 91 37 36

Still On Treatment 7 18 4 10

Treatment Ended 37 73 33 21

Released on Treatment 0 3 0 1

Discontinued 1 3 0 0

Completed 36 (97%) 67 (92%) 33 (100%) 20 (95%)

SVR Achieved 18 (95%) 47 (94%) 21 (100%) 12 (100%)

SVR Not Achieved 1 3 0 0

SVR N/A 17 17 12 8

N=312* Missing treatment history (n=25)

4: HCV Results: G1 on Harvoni (n=233)Treatment Outcome by Fibrosis

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Outcome* F0-F2 F3 F4

Initiated 34 84 113

Still On Treatment 5 20 17

Treatment Ended 29 64 96

Released on Treatment 1 1 4

Discontinued 1 0 4

Completed 27 (93%) 63 (98%) 88 (92%)

SVR Achieved 17 (89%) 35 (97%) 55 (98%)

SVR Not Achieved 2 1 1

SVR N/A 8 27 32

N=312* Missing fibrosis (n=2)

4: HCV Results: G1 (n=261)Treatment Outcome Summary

• Majority of patients had moderate or severe fibrosis (83% with F3 / F4)

• Majority of patients with G1 were treated with Harvoni

• Discontinuation (n=6, 2%) was seen infrequently– 4 of 6 due to non-adherence (1 due to side effects, 1 unknown)

• Early preliminary results indicate overall treatment success of SVR 113/118 (96%)– Non-SVR observed among treatment naïve

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4: HCV Results: G2&G3 (n=51)By Fibrosis

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FibrosisNumber of Sovaldi Treatment Starts

G2 G3 Total

F0 0 1 1

F1 1 2 3

F2 4 3 7

F3 3 5 8

F4 1 31 32

Total 9 42 51

N=312

4: HCV Results: G2&G3 (n=51)Treatment Outcome by Genotype

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OutcomeSovaldi

G2 (12wks) G3 (24wks)

Initiated 9 42

Still On Treatment 2 10

Treatment Ended 7 32

Released on Treatment 0 3

Discontinued 0 3

Completed 7 (100%) 26 (81%)

SVR Achieved 4 (100%) 14 (88%)

SVR Not Achieved 0 2

SVR N/A 3 10

N=312

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Outcome F0-F2 F3 F4

Initiated 11 8 32

Still On Treatment 1 2 9

Treatment Ended 10 6 23

Released on Treatment 0 1 2

Discontinued 1 0 2

Completed 9 (90%) 5 (83%) 19 (83%)

SVR Achieved 7 (100%) 3 (100%) 9 (82%)

SVR Not Achieved 0 0 2

SVR N/A 2 2 8

N=312

HCV Results: G2&G3 on Sovaldi (n=51)Treatment Outcome by Fibrosis

4: HCV Results: G2&G3 (n=51)Treatment Outcome Summary

• Majority of patients had moderate or severe fibrosis (78% with F3 / F4)

• Discontinuation of treatment (n=3, 4%) very infrequent

– 2 of 3 due to non-adherence (G3 24-wk)

• Early preliminary results based on small numbers indicate overall SVR 19 / 21 (90%) treatment success with Sovaldi

– Non-SVR associated with G3, F4 patients

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5: Summary

• New all-oral DAA medications are well tolerated and discontinuation due to side effects is minimal.

• Treatment outcomes using the new all-oral DAA medications of 90-95% were observed in a patient group characterized by moderate to severe fibrosis.

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Questions?

Jonathan Smith

Manager, Epidemiology Services

613-720-3768

jonathan.smith@csc-scc.gc.ca

Harold Boudreau

National Pharmacist

613-996-7437

harold.boudreau@csc-scc.gc.ca

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Emily Kom

Epidemiologist

613-992-9856

emily.kom@csc-scc.gc.ca

Tara Tremblay

Operations Supervisor

613-992-8801

tara.tremblay@csc-scc.gc.ca