Transcript opiCare

Jason Grebely, PhD
Lecturer
Viral Hepatitis Clinical Research Program
National Centre in HIV Epidemiology and Clinical
Research
University of New South Wales
Treatment of HCV infection
among active IDUs
Hepatitis C treatment
Sustained virologic response
?
PEG-IFN+RBV
24-48 weeks
61%-65%
IFN-α2b+RBV
48 weeks
PEG-IFN
48 weeks
IFN-α2b
48 weeks
IFN-α2b
24 weeks
41%
25%-29%
15%-22%
8%-12%
10 years
Management of Hepatitis C
• 1997 NIH Consensus Development Conference
Statement:
“treatment of patients who are drinking significant
amounts of alcohol or who are actively using illicit
drugs should be delayed until these habits are
discontinued for at least 6 months”
National Institutes Of Health Consensus Development Conference Statement. March 2426, 1997. Available at: http://consensus.nih.gov/1997/1997HepatitisC105html.htm
Accessed September 19, 2009.
3
Treatment of HCV in IDUs
• Treatment initiated during opiate
detoxification treatment (n=50)
100
– IFN alfa-2a (n=34)
– IFN alfa-2a + RBV (n=16)
90
80
• Drug use:
• Treatment completion: 46%
• Overall SVR: 36%
SVR (%)
– ICD-10 opiate dependency
– 36% cocaine (>weekly)
60
50
– SVR: 24% vs 53%
45%
40
30
20
10
• 80% relapsed to drug use
P<0.05
70
6%
0
>2/3
<2/3
Appointments Appointments
4
Backmund et al. Hepatology 2001.
Treatment of HCV in IDUs
• Treatment of HCV during methadone maintenance
therapy (interim analysis)
• IFN alfa-2b + RBV (n=50)
• Mean age 50, 62% psych history, 62% markers of
advanced disease, 52% genotype 1
• 78% completed HCV treatment
100
P>0.05
ETR (%)
80
60
70%
54%
51%
36%
40
20
0
Overall
G1
Sylvestre D, et al. Drug and Alcohol Dependence 2002.
Non-G1
Poynard 1998
McHutchison 1998
5
NIH Revises Recommendations
• 2002 NIH Consensus Statement:
– Management of HCV is enhanced by linking to drugtreatment programs
– Methadone is not a contraindication to HCV treatment
– HCV treatment of active IDUs should be considered on
a case-by-case basis
– Active IDU in and of itself should not exclude such
patients from antiviral therapy
NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002.
Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html. Accessed
September 19, 2009.
6
Treatment uptake among IDUs is still low
n
Canada (Vancouver)
United States (Baltimore)
Australia
Cohort
HCV
Treatment
Uptake/Year
1,360
Community-based inner
city residents
<1%
597
Community-based IDUs
<1%
Needle exchange
participants
1%
2,500
Grebely J, et al. J Viral Hepatitis 2009. Mehta S, et al J Community Health 2008. National
Centre in HIV Epidemiology and Clinical Research 2008.
7
IDUs demonstrate high HCV treatment willingness
Stein MD, et al. Drug and Alcohol Dependence 2001. Walley AY, et al. J Substance
Abuse Treatment 2005. Doab A, et al. Clinical Infectious Diseases 2005. Fischer B, et al.
Presse Med 2005. Strathdee S, et al Clinical Infectious Diseases 2005. Grebely J, et al.
Drug and Alcohol Dependence 2008.
8
Barriers to seeking treatment for HCV infection
Self-reported current HCV
positive status (n=188)
Never sought treatment for HCV
infection (n=107, 57%)
• The major reasons for not having sought treatment were:
– Lack of information/did not know that treatment was
available (23%)
– Absence of symptoms (20%)
– Perceived side effects of treatment (14%)
– Mild liver disease (10%)
– Other medical co-morbidities (8%)
– Lack of interest in treatment (3%)
9
Grebely J, et al. Drug and Alcohol Dependence 2008.
Barriers to HCV treatment uptake are multi-factorial
• Barriers to HCV treatment access may relate to:
– lack of knowledge and low prioritisation among
patients
– limited HCV treatment infrastructure, particularly in
settings of drug dependency treatment
– lack of treatment consideration or active
discrimination by clinicians
10
Remains a reluctance to treat IDUs for HCV
• Concerns of:
–
–
–
–
–
Adherence
Ongoing drug use
Relapse to substance use
Risk of exacerbation of co-morbid psychiatric disease
Perceived risk of HCV reinfection following successful
treatment
11
Treatment of HCV in IDUs
• Median SVR
– Regardless of treatment regimen: 40.6%
– Peg-IFN alfa + RBV: 54.3%
12
Hellard M, et al. Clinical Infectious Diseases 2009.
Impact of adherence on SVR
• Methadone maintenance (n=71)
• IFN alfa-2b+RBV
• Adherence: 80/80/80
100
90
80
• 59% used illicit drugs during
treatment
– 35% used heroin, cocaine, or
methamphetamine
SVR (%)
70
P=0.001
60
50
42%
40
30
20
• 68% (n=48) were adherent
4%
10
0
Adherent
Nonadherent
13
Sylvestre D, et al. European Journal of Gastroenterology and Hepatology 2007.
Impact of ongoing drug use on adherence
14
Sylvestre D, et al. European Journal of Gastroenterology and Hepatology 2007.
Discontinuation occurs early in therapy
• Observational study of MMT (n=50) vs. controls (n=50)
• SVR was 42% in MMT vs. 56% in controls
• No significant increase in methadone dose during therapy
Methadone - All
Methadone - Noncompliance
Controls - All
Controls - Noncompliance
15
Mauss S, et al. Hepatology 2004.
Treatment completion
• Median completion overall: 70.7%
• Only 1 of 5 evaluable studies demonstrated a difference in
treatment completion rates in IDUs vs. non-IDUs
16
Hellard M, et al. Clinical Infectious Diseases 2009.
Adherence
• Poor data on adherence
• Varying definitions of adherence makes it difficult
to compare studies
17
Hellard M, et al. Clinical Infectious Diseases 2009.
Adherence failure….
A “bad patient?” or …
... our failure to design a treatment program which
works for that individual
18
Directly observed therapy for HCV
Study Design:
•
Open label, prospective, observational trial
Primary Endpoint:
•
Proportion with undetectable HCV RNA 6 months after treatment (SVR)
Interferon alfa-2b 3 MIU 3x/week
+ Ribavirin 800-1200 mg/day
(n = 12)
N = 40
Peginterferon alfa-2b 1.5 µg/kg/week
Week 48 for
genotype 1;
Week 24 for
genotypes 2/3
+ Ribavirin 800-1200 mg/day
(n = 28)
Medication administration:
•
IFN (3x week) and PEG-IFN (1x week) were administered as DOT
•
RBV self-administered
19
Grebely J, et al. Journal of Gastroenterology and Hepatology 2007.
Directly observed therapy for HCV
•
•
•
•
Mean age 43, 83% male, 55% genotype 2/3
Early discontinuation - 11 patients (28%)
35% used illicit drugs in the last 6 months
48% used illicit drugs during treatment
20
Grebely J, et al. Journal of Gastroenterology and Hepatology 2007.
Impact of prior and ongoing IDU on SVR
• 35% used illicit drugs in the last 6 months
• 48% used illicit drugs during treatment
• “frequent” – greater than weekly
21
Grebely J, et al. Journal of Gastroenterology and Hepatology 2007.
Impact of prior and ongoing IDU on SVR
• IFN alfa-2b + RBV during methadone maintenance (n=76)
• 36% used illicit drugs during treatment
• “frequent” - everyday or every other day for a min of 1 month
22
Sylvestre D, et al. Journal of Substance Abuse Treatment 2005.
Impact of IDU and adherence on SVR
• Australian Trial in Acute Hepatitis C Study (n=109), 74 HCV
23
Dore G, et al. Gastroenterology 2010.
Enhancing HCV treatment through peer support
• From March 2005 to 2008, HCV-infected individuals were
referred to a weekly peer-support group and assessed
for HCV infection (n=204 accepted referral).
• Assessment for HCV in 53%
• The first 4 weeks of support group attendance predicted
successful HCV assessment (OR: 6.03, 95% CI:3.27–11.12,
P<0.001)
• Treatment for HCV was initiated in 28% (n=57)
24
Grebely J, et al. J European Gastroenterology and Hepatology 2009 (In Press).
Conclusions
• Treatment of HCV among current and former IDUs is effective
– Studies to date are limited by small sample size and absence of
prospective, longitudinal data collection
• Treatment completion/adherence
– Comparable rates of treatment completion between IDUs and non-IDUs
– Adherence has an impact on SVR
• Drug use during treatment
– Drug use prior to treatment is not associated with reduced SVR
– Frequent drug use may be associated with reduced response to therapy
– Cannot predetermine who will discontinue due to drug use prior to initiation
of treatment
– Must evaluate patients on a case by case basis
25
There is still much to learn....
• Current uptake of assessment and treatment among
IDUs is still unacceptably low
– Why are IDUs assessed for HCV infection not receiving treatment?
• Treatment is effective
– What factors are associated with response?
• Treatment completion/adherence
– Evaluation of strategies to enhance adherence (e.g. Individualized
treatment, DOT)
• Drug use prior to and during treatment
– What is the impact of drug use on treatment for HCV infection?
• There is still concern about HCV reinfection following
HCV treatment
– Factors associated with reinfection?
26