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.

Presentation Outline Overview of CSC HCV Epidemiology in CSC CSC Formulary HCV Treatment - Results Summary

1: Overview of CSC Corrections and Conditional Release Act 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)

1: Overview of CSC CSC Regions (Moncton)

2: HCV Epidemiology in CSC HIV and HCV Testing on Admission Preliminary Unpublished Data, CSC 2014

2: HCV Epidemiology in CSC Newly Diagnosed HCV on Admission

2: HCV Epidemiology in CSC Year-end HCV Prevalence by Gender

2: HCV Epidemiology in CSC HCV Treatment Initiation All oral DAA Therapy Introduced (e.g. Harvoni) 1st Gen Triple Therapy Introduced (e.g. boceprevir + peginterferon + ribavirin)

3: CSC Formulary HCV 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)

3: CSC Formulary HCV 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

4: HCV Treatment - Results Methods 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)

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

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%

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 Compares to 17% retreatment pre interferon-free regimens Compares with 12 / 229 (5%) were reinfection pre interferon-free regimens

4: HCV Treatment - Results Genotype Frequency Proportion G1 260 83% G2 9 3% G3 42 13% G4 1 <1% TOTAL 312 G1 includes coinfected patients (n=4)

4: HCV Results: G1 (n=261) Treatment Regimen by Fibrosis Number of Treatment Starts* Harvoni Sovaldi Holkira Pak Total F0 F1 2 1 3 F2 32 5 37 F3 84 94 F4 113 7 125 233** 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 Harvoni Sovaldi Initiated 233 18 Still On Treatment 44 1 Treatment Ended 189 17 Released on Treatment 6 2 Discontinued 5 Completed 178 (94%) 14 (82%) SVR Achieved 107 (96%) 6 (86%) SVR Not Achieved 4 SVR N/A 67 7 N=312 Holkira 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 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 73 33 21 Released on Treatment 3 1 Discontinued Completed 36 (97%) 67 (92%) 33 (100%) 20 (95%) SVR Achieved 18 (95%) 47 (94%) 21 (100%) 12 (100%) SVR Not Achieved SVR N/A 17 12 8 N=312 * Missing treatment history (n=25)

4: HCV Results: G1 on Harvoni (n=233) Treatment Outcome by Fibrosis F0-F2 F3 F4 Initiated 34 84 113 Still On Treatment 5 20 17 Treatment Ended 29 64 96 Released on Treatment 1 4 Discontinued Completed 27 (93%) 63 (98%) 88 (92%) SVR Achieved 17 (89%) 35 (97%) 55 (98%) SVR Not Achieved 2 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

4: HCV Results: G2&G3 (n=51) By Fibrosis Number of Sovaldi Treatment Starts G2 G3 Total F0 1 F1 2 3 F2 4 7 F3 5 8 F4 31 32 9 42 51 N=312

4: HCV Results: G2&G3 (n=51) Treatment Outcome by Genotype Sovaldi G2 (12wks) G3 (24wks) Initiated 9 42 Still On Treatment 2 10 Treatment Ended 7 32 Released on Treatment 3 Discontinued Completed 7 (100%) 26 (81%) SVR Achieved 4 (100%) 14 (88%) SVR Not Achieved SVR N/A N=312

HCV Results: G2&G3 on Sovaldi (n=51) Treatment Outcome by Fibrosis F0-F2 F3 F4 Initiated 11 8 32 Still On Treatment 1 2 9 Treatment Ended 10 6 23 Released on Treatment Discontinued Completed 9 (90%) 5 (83%) 19 (83%) SVR Achieved 7 (100%) 3 (100%) 9 (82%) SVR Not Achieved SVR N/A N=312

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

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.

Operations Supervisor 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 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