Transcript Presenting

Challenges of Treatment of Hepatitis
C in the Incarcerated US Population
USPHS Scientific and Training Symposium
June 23, 2011
Dr William Resto-Rivera MD, USPHS
Kiesha Resto Pharm D, USPHS
Objectives
#1) Compare Hepatitis C Virus (HCV) infections in prison
population versus the regular population.
#2) Analyze the challenges of identifying and treating prison
population.
#3) Review common & rare side effects that are related to
Hepatitis C therapy.
#4) Discuss challenges in treating patients with co-morbid
conditions.
#5) Review recent FDA approved medications for HCV.
US Hepatitis Statistics
1.3%
• US population infected Hepatitis C
Virus (HCV)
• People infected with HCV will pass
through
US
prison
system
every
year
29-43%
• US Prison population infected with
16-40% HCV
Reference #4
Population
•
Baby boomers account for 2 out of 3 cases of HCV
patients.
•
Peak prevalence men born in early 1950’s
•
HCV is over-represented in African Americans.
Reference #5
Every 100
people infected
with HCV
75-85 develop
chronic
infection
5-20 develop
cirrhosis
60-70 develop
chronic liver
disease
1-5 die from
cirrhosis or
liver cancer
Center of Disease Control & National Institutes of
Health Convention January 2003 identified 5 optimal
approaches to Screening & treating HCV in US
prisons
•
#1 Testing of HCV in Prisons would identify many Infected
Americans
•
#2 Prison Substance Abuse programs would decrease HCV
infections & future prisons cost
•
#3 Patients can be Selected using Published Guidelines
•
#4 Prisons Treatment Reflects Community Standards and
Require Sufficient Medical Workforce
•
#5 Collaboration Between Correctional & Public Health
Systems is Needed
Reference #14
Factors for Treatment
•
Screening
• Screening and Diagnosis of Hepatitis C
individuals.
• Screening for candidates for treatment
•
Safety , Efficacy & Cost
• Monitoring Laboratories and ADR
• Patient Tolerate treatment
• Viral Response to treatment
• EVR/SVR
• Source of funding
Hepatitis C Not a Routine
Universal Screening
Routine screening based on 4 criteria:
•
•
•
•
Amenable to treatment
Interfere with activities of daily living
Progress without treatment during time of
incarceration
Risk of transmission
Reference # 14
To Screen or to Not Screen
Rhode Island State
Corrections
Screened all incoming inmate
•
4263 Males – 23% + HCV
•
499 Females – 40% HCV
Out of inmates who tested + HCV
66% did not report high risk
behaviors
Reference #16
Wisconsin State Corrections
91% HCV infected inmates
identified through testing 27%
of population with risk factor
IVDA
Indiana State Corrections
Universal testing found 13%
of population HCV (+)
Reference #14
USA and territories Incarcerated population
2008
Total
Federal & State Prisons
Territorial Prisons
Local Jails
2,424,279
1,518,559
13,576
785,556
ICE Facilities
9,957
Military Facilities
1,651
Jails in Indian Country
2,135
Juvenile Facilities
92,845
Reference #3
Break down of
2,424,279
16-40%
1 to 3 %
• US prison population
infected with HCV
387,884 -- 969,711
• Progress to end stage
liver disease
3,878 -- 29,091
Summary of Assumptions of Paid
Cost per Patient Per Month
(PPPM) as of 2008
Reference #22
Medicare
Disease States
Commercial
Age<65
Age >65
$525 more than avg
$460 more then avg
$370 more than avg
$772 more then avg
$611 more than avg
$13,900
$7,100
$7,100
$12,700
$4,200
$4,200
$5,500
$2,400
$2,400
$4,900
$2,100
$2,100
$38,900
$24,700
$24,700
$5,600
$3,800
$3,800
$3,900
$2,200
$2,200
$174 more than avg
Chronic HCV Infection (without Cirrhosis)
Compensated Cirrhosis without Complication
Decompensated Cirrhosis
6 months
0-
Decompensated Cirrhosis
months
+6
Hepatocellular Carcinoma
months
Hepatocellular Carcinoma
months
Liver Transplant
6 months
Liver Transplant
18 months
Liver Transplant
18 months
0-6
+6
06+
Missed Opportunity
Benefits for treatment during Incarceration
•Lower cost in long run for HCV treatment
•Stable living environment
•Accessible medical care
•High Risk Population
•Direct Observed Medication
•Abstinence from Substance abuse
•Coordination between Rehabilitation programs and
treatment
Hepatitis C
•
•
Multiple Genotypes
•
1 Most common (US) Approx. 80%
•
2/3 US Approx 20%
•
4 Egypt
RNA Virus
•
Family Flavovirus ( Denque, yellow fever)
US Hepatitis C Statistics
•
Genotype 1
40-50% Successful SVR at 12 months
•
Genotype 2/3
70-80% Successful SVR at 12 months
Contraindications to
Ribavirin
1.
Thalassemias (sickle cell anemia) or other
hemoglobinopathy.
2.
Significant cardiac disease (arrhythmias, angina,
CABG, MI) in the past 12 months.
3.
Renal dialysis or creatinine clearance < 50
mL/min.
4.
5.
Hypersensitivity to ribavirin
Pregnancy
Reference #1
Ribavirin Side Effects
Black Box Warnings:
•
Hemolytic Anemia Warning (primarily in the first two
weeks of therapy)
•
Pregnancy Warning. Negative pregnancy test is
required pre-therapy & at every evaluation
•
Respiratory Warning for patients requiring assisted
ventilation
Reference #1
Contraindication Peg-Interferon
•
Serious concurrent medical diseases;
severe hypertension, heart failure, coronary heart disease, COPD , autoimmune
disorders, uncontrolled endocrine disorder
•
Decompensate cirrhosis, History of solid organ transplant
•
Platelet count <75,000/mm3 or ANC <1,500 cells/mm3
•
Ongoing injection drug use or alcohol use
•
Severe uncontrolled psychiatric disease
Reference #1
Carswell 20072010
Statistical Data:
Annals Internal
Medicine 2004 (6)
Statistical Data:
Hematology 2002 (7)
26%
55%
64%
63%
25%
63%
21%
32%
42%
35%
43%
63%
48%
64%
Mood Changes
42%
26%
35%
Gastro-intestinal
21%
20%
Adverse Event
Headache
Pruritis
Decrease Appetitie
Nausea / vomiting
Fatigue
Anemia
Neutropenia
Thrombocyto
42%
22%
21%
20%
21%
4%
Reference # 6 & #7
Management of Side
Effects
•
Headaches/ Body aches
•
•
Tylenol
•
FLUIDS, FLUIDS, FLUIDS
•
NSAIDS!!!???
Nausea & Vomiting
•
Promethazine
Hemoglobin
adjustment
10-11 g/dl
8.5-10 g/dl
<8.5 g/dl
If no or minimal symptoms, then no dose modification
If symptomatic, decrease ribavirin by 200 mg/day
Peginterferon alfa 2b ( Peg-Intron) Reduce 25-50%
Ribavirin ↓ to 600 mg daily (200 mg AM & 400mg PM)
Peginterferon alfa 2b (Peg-Intron) Discontinue until
resolved.
Ribavirin Discontinue until resolved.
If hemoglobin is <12g/dL for over 4 weeks at the
reduced/adjusted dose then discontinue ribavirin
Reference #1
Absolute Neutrophil Count (ANC)
Adjustment
<750
Peginterferon alfa 2b (Peg-Intron) Reduce to a
25% -50% dose
<500
Peginterferon & Ribavirin Discontinue both until
resolved
Granulocyte Colony Stimulating Factor (G-CSF): If the patient is responding to treatment
and neutropenia persists despite reduced peginterferon dose, consider G-CSFDosage:
Filgrastim 300 microgram subcu. daily. Goal: ANC >1500
Reference #1
Platelet Adjustment
<50,000 Peginterferon alfa 2b (Peg-Intron)
<30,000
Discontinue until resolved.
Ribavirin If on Peg-Intron, then discontinue
ribavirin.
Peginterferon Discontinue until resolved.
Ribavirin Discontinue until resolved.
Reference #1
Serious Adverse
Reaction
•
Auto immune
•
Arrhythmias
•
Depression / Psychosis
•
CHF
•
Permanent thyroid dysfunction
Patients with Comorbid conditions
•
Pre-exiting Cardiac Condition
•
Renal Disease
•
Autoimmune Disease
•
Depression
Case Studies
Digest of Liver
Disease 2011
Nephrology,
Dialysis,
Transplant 2003
Journal of
Rheumatology
1996
• Tx 23 pre-existing heart disease patients with INF &
Ribavirin
• 52% reached SVR, 39% relapse, 9% non responders
• EKG & Echo show no signs of progression of preexiting heart disease
• Tx 7 patients with vasculititis and GN
successfully with INF & Ribavirin
• 19 patient referred from PCP for polyarthritis,
polyarthralgia, or positive rheumatoid factors where
found to have hepatitis
Reference # 8-#10
New Treatment
Options
Boceprevir ( Victrelis)
•
•
•
•
FDA approved May 13, 2011
Hepatitis C Genotype 1
Naïve & Relapse patients
800 mg tablets x 44 weeks after 4 week lead in
Telaprevir (Incivek)
•
•
•
•
FDA approved May 23, 2011
Hepatitis Genotype 1
Naïve and Relapse patient
750 mg tablets TID for first 12 weeks of therapy
Telaprevir (Incivek)
• Naive &
Relapser (1088)
• Treatment
75% SVR
• Control 45%
SVR
ADVANCE
• Naïve ( 704)
• Treatment 80%
SVR
• Control
50%
SVR
• No benefit
extending tx
• 92% SVR @
24wks
• 88% SVR @
48wks
ILLUMINATE
• Relapsers
(650)
• Treatment
56% SVR
• Control 22%
SVR
REALIZE
Reference #20
Boceprevir (Victrelis)
SPRINT-2
RESPOND2
• Treatment Naïve (1,097)
• Treatment Group 69% SVR
Control Group 40% SVR
• African American
Treatment 69%SVR
Control 40% SVR
• Non-Responders and
Relapsers (403)
• Treatment Group 66% SVR
Control Group 21% SVR
Reference #21
Adverse Effects
Boceprevir (Victrelis)
• Fatigue, Headache, Nausea, Dysgeusia
• Anemia (3% require discontinuation of therapy)
Telaprevir (Incivek)
• Fatigue, Headache, Nausea, Pruritis
• Anemia & Rash ( 0.6-1.1% require discontinuation of
therapy)
Summary
•
Prison are an ideal setting to treat a large
population of HCV (+) people.
•
Screening for HCV need to be examined
cost/benefit per institution.
•
Treating patient while incarcerated can be a cost
saving to society
•
HCV treatment is associated with multiple side
effects that need an educated multidiscipline
approach to manage
Summary
•
Guidelines are established for screening and to
help guide management of adverse events.
•
Patient with co-morbidies are an increase
challenge to treat but can be treated safely and
effectively with proper monitoring.
•
New Antiviral medications just approved will
improve overall outcomes in the future.
References
1.
Federal Bureau of Prisons Clinical Guideline Prevention of Hepatitis C and Cirrhosis June 2009
2.
Raison. Depression During Pegylated Interferon-Alpha Plus Ribavirin Therapy: Prevalence and Prediction. J Clin
Psychiatry. 2005 January ; 66(1): 41–48. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615913/pdf/nihms3152.pdf (
Accessed 4/11)
3.
http://en.wikipedia.org/wiki/Incarceration_in_the_United_States (Accessed 9/24/10)
4.
Jennifer A. Tan, Tom A. Joseph, Sammy Saab, Treating hepatitis C in the prison population is cost-saving
,Hematology . 2008; 48: 1387-1395
5.
Suzanne M. Kirchhoff, Economic Impacts of Prison Growth, Congressional Research Service, April 13, 2010.
http://assets.opencrs.com/rpts/R41177_20100413.pdf (Accessed 9/24/10 )
6.
Hadziyannis, S. Peginterferon-2a and Ribaviriin Combination Therapy in Chronic Hepaitits C. Annals of Internal
Medicine. 2004 ;140: 346-357
7.
Fried, M. Side Effects of Therapy of Hepaptitis C and Their Management. Hepatology. 2002: 36.
References
8.
Bruchfeld, A. Lindahl, K. Interferon and Ribavirin treatment in patients with hepatitis C-associated renal disease
and renal insufficiency. Nephrology Dialysis Transplantation, 2002;18, 1573-1580.
http://ndt.oxfordjournals.org/content/18/8/1573.short ( Accessed 4/2011)
9.
EL-Atrebi, K. El-Bassyouni, H. Management of rare side effects of peginterferon and ribavirin therapy during
hepatitis C treatment: a case report. Case Journal 2009:2 : 7429
10.
Lovy M.R, Starkemaum G. Hepatitis C Infection Presenting with Rheumatic Manifestations: Mimic of
Rheumatoid. Journal of Rheumatology 1996; 23;979-983
11.
Center of Disease Control Morbidity and Mortality Weekly Report. Prevention and Control of Infections with
Hepatitis Viruses in Correctional Settings. January 24, 2003 / Vol. 52 / No. RR-1
12.
Durante-Mangoni E, Iossa D. Safey and efficacy of peginterferon alpha plus ribavirin in patients with chronic
hepatitis C and coexisting heart disease. Dig Liver Dis 2011 [ pub ahead of print].
13.
Ghany M, Strader B. Diagnosis, Management, and Treatment of Hepatitis C: An Update. HEPATOLOGY 2009; 49:
1335-74
References
14.
Spaulding A, Weinbaum C. A Framework for Management of Hepatitis C in Prisons. Annals of Internal Medicine
2006; 144: 762-769
15.
15. Kim R. The Burden of Hepatitis C in the United States. Hepatology 2002;36:S30-S34
16. Macalino G. A Missed Opportunity: Hepatitis C Screening of Prisoners. AM J Public Health. 2005;95: 1739-1740
17. Sutton A, Edmund J. Estamating the cost-effectiveness of detecting cases of chronic hepatitis C infection on
reception into prison. BMC Public Health 2006;6;170
18. Mc Hutchinson J, Brunce B. Chronic Hepatitis C: An Age Wave of Disease Burden. Am J Manag Care
2005;11:S286-S295
19. Wong J, McQuillan G. Estimating Future Hepatitis C Morbidity Mortality, and Cost in the United States. Am J Public
Health. 2000;90:1562-1569
20. http://www.hivandhepatitis.com/hep_c/news/2011/0524_2011_a.html ( Accessed 6/2/11)
References
•
22. B. Pyenson. Consequences of Hepatitis C virus (HCV): Cost of a Baby Boomer
Epidemic of Liver Disease. Vertex Pharmaceuticals Incorporations. Miliman, Inc. May 2009.
QUESTIONS ??