Treatment of Hepatitis C in People Who Inject Drugs (PWIDs) Andrew Seaman, MD OHA P&T Meeting January, 2017

Transcription

1 Treatment of Hepatitis C in People Who Inject Drugs (PWIDs) Andrew Seaman, MD OHA P&T Meeting January, 2017

2 Conflicts of interest Receive <8% of my salary from an investigator initiated, Merck funded trial (makers of elbasvir/grazoprevir) I am highly influenced by the opinions, life experience, and knowledge my patients bring to the table (many of whom inject drugs)

3 Objectives Review of published and some unpublished data on PWIDs from colleagues in New York, Australia, Europe Brief review of the Old Town Clinic / Outside In / OHSU pilot trial for HCV treatment in People Who Inject Drugs

4 Alcohol use does not affect SVR12 Tsui et al. Drug Alcohol Depend Dec 1;169:

5 C-EDGE CO-STAR Trial Multicenter-RCT tx w/ Elb-Graz with 301 PWIDs Patients with GT 1, 4, or 6 HCV on either methadone (81%) or buprenorphine (19%) for comorbid opioid use disorder Randomized 2:1 to immediate treatment group vs delayed treatment group (12wks placebo + 4 weeks de-randomization + 12 weeks treatment) Primary outcome SVR 12 assuming re-infection as cure Intention-to-treat analysis Dore et al. Ann Intern Med. 2016;165:

6 C-EDGE CO-STAR Trial Imm. Treat. Group (n=201) Assuming Reinfections are Responses Assuming Reinfections = Treatment Failure SVR 12 SVR 24 94% ( ) 85% ( ) 91.5% (CI %) *2/201 additional relapses 87% Probable Reinfection 5/201 5/201 Lost to Follow Up 3 15 Adherence >95% ~95% 95% **2 year f/u re-infection data 2.3/100pyrs Dore et al. Ann Intern Med. 2016;165:

7 SIMPLIFY trial (pre-publication) Multicenter, international RCT with recent (<6mo) PWIDs 103 participants w/ GT 1-6 HCV Treated w/ Sof/Vel x 12 weeks Primary endpoint SVR12, secondary Adherence > 90% Results 70% injecting in last month 57% receiving opioid substitution therapy End Treatment Response 94% (NO confirmed VL failures 6% loss to f/u) SVR12 and Adherence data pending Reinfection data pending (f/u 3 years) Grebely et al. Hepatology. 2017Volume 66, Issue 1, Supplement, Page S513

8 Intensive management of HCV tx in PWIDs: Montefiore trial PREVAIL study: Unpublished data from INHSU. LINK to slides.

9 OTC OI OHSU Pilot Study Prospective, non-randomized real world clinical trial using elb/graz to treat people who inject drugs with GT 1 or 4 HCV and an APRI <0.7 who: Arm 1: engage with Medication Assisted Therapy (Methadone/Bupe), n=25, Old Town Clinic Arm 2: are actively using and engage with needle exchange program, n=25, Outside In Arm 3: matched cohort in OHSU hepatology clinic, n=50

10 Endpoints Primary SVR 12 and 48 Secondary Primary Tx failure (+RNA 24wks) Secondary Tx Failure (+RNA 60wks) Adherence Discontinuation rate NS5a resistance Substance use relapse

11 OHSU-OTC-OI Study Progress: Enrollment Old Town Clinic / MAT: 25/25 enrolled Adherence greater than 95% (All patients completed by Jan, SVR data by April 1) Outside In 14/25 enrolled Adherence good except 2/10 lost-to f/u (? Sampling error) OHSU Pending

12 Limitations Power Powered to detect a difference of 20% in primary endpoint; this is not clinically ideal Group Disparities Comparing prospective trial w/ very specific inclusion criteria to chart biopsy based cohort Difference in un-measurables between people in MAT program and needle exchange (and university setting) Differences in pre-screening process

13 Old Town Clinic Treatment Program Multidisciplinary Medical director + two providers HCV coordinator Clinical pharmacist CADC Weekly committee meetings Decision made on need for treatment candidacy, Substance Used Disorder support, adherence support Drug, labs ordered and PA process started by coordinator First, last, and SVR visit by provider, remainder by pharmacist

14 We treat everyone Treatment candidacy Made 2/3 last appointments or subjective adherence measure (whichever lower barrier) Desires treatment Meets their insurance eligibility criteria* *We consider any SUDs support as treatment and have had great success with insurers

15 Our capacity A total of 60 patients have initiated treatment in the last 9.5 months (24 study/36 non-study). We expect to treat many more in HCV Treatment Initiation 2017 OTC HCV Treatment Snapshot Mar Apr May Jun Jul Aug Sep Oct Nov Dec Program Study Both Linear (Program) Started Tx (60) Finished Tx (32) Active Tx (27) Discontinued (1) Program Study

16 Adherence Adherence has been near perfect in almost all cases. The 4 exceptions are: #1 completed 1 month interruption, #2 discontinued completed 8 weeks, #3 active 15 day interruption & #4 active 24 day interruption. Adherence - Not active 6.7% 93.3% Great Adherence (28) Adherence Issues (2)

17 Treatment efficacy Everyone that completed a SVR12 viral load has been undetectable. HCV SVR Due for lab (15) Results received (12) SVR12 achieved (12) Program Study

18 Treatment as prevention depends on treating PWIDs Despite reinfection risk, not treating leads to a greater public health risk If we are not treating a patient population with at least some reinfection risk we are not treating the population that transmits this virus Multiple models suggest that we must treat PWIDs if we are to successfully address the HCV epidemic 9,10

19 In Summary: We can and must treat hep C in PWIDs There is no evidence of different hepatitis C treatment outcomes among people with or without substance use disorders The WHO and others recommend we prioritize rather than restrict treatment in PWIDs Mathematical models and common sense suggest we cannot treat this epidemic unless we treat the people transmitting the virus Where is the rational for denying people with substance use disorders?? The rational for 6 months sobriety? (Why not deny diabetics? People with metabolic syndrome? Tobaccoism?)

20 HCVguidelines.org

21 Questions?

22 References 1. Centers for Disease Control and Prevention. Viral Hepatitis Surveillance United States, E Paintsil, H He, C Peters, and others. Survival of HCV in Syringes: Implication for HCV Transmission among Injection Drug Users. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, Abstract Platt L, Minozzi S, Reed J, Vickerman P, Hagan H, French C, Jordan A, Degenhardt L, Hope V, Hutchinson S, Maher L, Palmateer N, Taylor A, Bruneau J, Hickman M. Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD Grebely et al. Efficacy and safety of sofosbuvir/velpatasvir in people with chronic hepatitis C virus infection and recent injecting drug use: the SIMPLIFY study. 2017Volume 66, Issue 1, Supplement, Page S Read et al. Delivering direct acting antiviral therapy for hepatitis C to highly marginalised and current drug injecting populations in a targeted primary health care setting. International Journal of Drug Policy 47 (2017) Tsui et al. Drug Alcohol Depend Dec 1;169: Dore et al. Ann Intern Med. 2016;165: Pineda et al. Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C. Infection. November 2015Volume 71, Issue 5, Pages

23 References Continued 9. Martin et al. Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatmentscale-up in the age of directacting antivirals. Hepatology Nov;58(5): Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, Vickerman P.Combination interventions to prevent HCV transmission among people who inject drugs: modeling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy. Clin Infect Dis. 2013;57(Suppl 2):S39-S Durier N, Nguyen C, White LJ. Treatment of hepatitis C as prevention: a modeling case study in Vietnam. PLoS One. 2012;7(4):e34548.