Transcript ABC`s Of Hepatitis C Treatment Readiness and Follow-up

ABC’s Of Hepatitis C
Treatment Readiness and
Follow-up
Geri Hirsch RN-NP
Nurse Practitioner Hepatology
[email protected]
Overview of Presentation
• HCV screening/testing
• Pretreatment counseling
• Encouraging adherence
• Managing adverse events
Screening
(1) Anyone with RISK
BEHAVIOURS/POTENTIAL EXPOSURES
to HCV
• High Risk
– Injection drug use (IDU)
– Incarceration
– Born, traveled, or resided in a region in which HCV
infection is more common
– Receipt of health care where there is a lack of
universal precautions (nosocomial transmission)
– Blood transfusion, blood products, or organ transplant
before 1992 in Canada
http://www.phac-aspc.gc.ca/hepc/pubs/pdf/hepc_guide-eng.pdf
(1) Anyone with RISK
BEHAVIOURS/POTENTIAL EXPOSURES to
HCV
• Intermediate Risk
– Hemodialysis
– Infant born to mother with HCV infection
– Needle stick injuries
• Other Risks Associated With HCV EXPOSURE
– Sharing sharp instruments/personal hygiene materials
– with HCV+ person (e.g., razors, scissors, nail clippers,
toothbrush)
– Tattooing, body piercing, scarification, female genital mutilation
or other ceremonial rituals
– Intranasal (snorting) & inhalation drug use
– Homelessness, residency in group homes or shelters
– Higher-risk sexual behaviour
http://www.phac-aspc.gc.ca/hepc/pubs/pdf/hepc_guide-eng.pdf
(2) Anyone with CLINICAL CLUES
suspicious for hepatitis C infection (and
above risk factors)
• Abnormal liver biochemistry
(e.g., ALT)
•
Drug and/or alcohol
dependency (past or present)
• Blood diseases requiring
multiple transfusions of blood
products (e.g., hemophilia,
thalassemia, sickle cell
• anemia)
•
• HIV infection
• Signs of chronic liver disease
(e.g., hepatomegaly +/• splenomegaly, spider nevi,
palmar erythema, jaundice)
• Vasculitis (due to associated
cryoglobulinemia)
• History of unexplained renal
impairment
HBV infection
• Non-Hodgkin’s lymphoma
http://www.phac-aspc.gc.ca/hepc/pubs/pdf/hepc_guide-eng.pdf
Hepatitis C Treatment
HCV Standard of Care Therapy:
Dosing Recommendations
Medication
HCV Genotypes 1 or 4
HCV Genotypes 2 or 3
180 μg/wk SQ
(hemodialysis: reduce to 135 μg/wk SQ)
PegIFN alfa-2a[1]
• Ribavirin[2]
200 mg tablets in 2 divided doses/day
• 1000 mg/day (< 75 kg)
• 1200 mg/day (≥ 75 kg)
• 800 mg/day
1.5 μg/kg/wk SQ
(If CrCl 30-50 mL/min: reduce dose by 25%;
if CrCl 10-29 mL/min: reduce dose by 50%)
PegIFN alfa-2b[3]
• Ribavirin[4]
200 mg capsules in 2 divided doses/day
•
•
•
•
≤ 65 kg: 800 mg/day
66-80 kg: 1000 mg/day
> 80-105 kg: 1200 mg/day
> 105 kg: 1400 mg/day
•
•
•
•
≤ 65 kg: 800 mg/day
66-80 kg: 1000 mg/day
> 80-105 kg: 1200 mg/day
> 105 kg: 1400 mg/day
1. Peginterferon alfa-2a [package insert]. 2010. 2. Ribavirin tablets [package insert]. 2010.
3. Peginterferon alfa-2b [package insert]. 2010. 4. Ribavirin capsules [package insert]. 2010.
HCV Genotype and Response
24 wks
RBV800mg/day+pegIFN alfa
2a
90
80
24 wks of RBV 1000/1200
mg/day +pegIFN alfa 2a
SVR (%)
70
48 wks
RBV800mg/day+pegIFN alfa
2a
60
50
48 wks of RBV 1000/1200
mg/day +pegIFN alfa 2a
40
30
20
10
0
Geno 1
Geno 2+3
Advanced Fibrosis
Geno1
Geno 2+3
Minimal Fibrosis
Hadziyannis SJ, et al. Ann Intern Med. 2004;140:346-355.
Current and Future Treatments
Future treatment
80
70
SVR (%)
60
Current treatment
50
40
30
20
10
0
Naïve
non responders
Naïve
non responders
1. Poordad F, et al. AASLD 2010. Abstract LB-4. 2. Jacobson IM, et al. AASLD 2010. Abstract 211. 3. Bacon BR, et al. AASLD
2010. Abstract 216. 4. These data are available in press release format only, have not been peer reviewed, may be incomplete,
and we await presentation or publication in a peer-reviewed format before conclusions should be made from these data.
Predictors of Treatment Response
Patient Factors
Virus Factors
• Age
• Genotype
• Sex
• HCV RNA level
• Race
• Weight
• Insulin resistance
• Fatty liver disease
• Mental health
• Drug/alcohol use
• Cirrhosis
• HIV coinfection
• IL28B status
Regimen Factors
• Adherence to pegIFN/RBV
• Weight-based RBV dosing
(genotypes 1/4)
• Reported improved response
rates with protease inhibitors
(in the future, for genotype 1
patients only)
Response Definitions in Patients
Receiving HCV Therapy
Response definitions Time Point
HCV RNA Level
Rapid virologic
response - RVR
4 wks into therapy
Undetectable
Early virologic
response - EVR
12 wks into therapy Undetectable (complete)
≥ 2 log decrease from
baseline (partial)
End of treatment
response - EOT
End of therapy
Sustained virologic
response - SVR
6 mos post therapy Undetectable
Ghany MG, et al. Hepatology. 2009;49:1335-1374.
Undetectable
Preparing the Patient for HCV
Therapy
• Provide and verify patient’s/family’s understanding of basic
information about
–
–
–
–
HCV transmission,
prognosis,
treatment,
adverse event management
• Obtain and discuss
– patient’s /family’s willingness
– adherence to medications
– need for visits/lab follow-ups
Preparing the Patient for HCV Therapy
• Social assessment
– housing,
– disability,
– social supports,
– transportation, finances, drug plan
• Educate
– alcohol, herbals,
– hepatotoxins,
– safe injection techniques*
• Ensure immunizations for HAV, HBV, pneumococcal, and seasonal
influenza
Preparing the Patient for HCV
Therapy
• Cautionary Uses
– Cardiovascular disease
– Autoimmune disease
• Cryoglobulinemia related symptoms
– Psychiatry history/suicide
– Alcohols and substance misue
– Other
• DM,seziure disorder,decomplenstated liver
disease ,renal diseasem lung disease, retinopathy,
hemoglobinopathies
Preparing the Patient for HCV
Therapy
• Provide and verify patient’s understanding of basic
information of side effect management
• Encourage patient’s/family’s active participation in
treatment decisions and ability to ask questions
• Review laboratory parameters and urine pregnancy test*
– Serum ALT, AST, bilirubin, alkaline phosphatase, albumin,
serum creatinine / BUN, TSH, glucose, urinalysis
– prothrombin time/INR,CBC with differential and platelet
count,HIV and hepatitis B surface antigen
– ANA*,genotype, viral load**,occular exam*
– weight
Preparing the Patient for HCV
Therapy
• Additional Tests
– Chest x ray, PA and LAT
– Cardiac assessment - EKG and in consultations with
MD consider a cardiology consult
– Mental Health Assessment
– Abdominal ultrasound
– Iron saturations (and hemochromatosis gene test if
indicated
– Serum cooper, ceruloplasmin, and alpha 1 if indicated
Preparing the Patient for HCV
Therapy
• Assure effective contraception and
reinforce issue of contraception
• Administer/demonstrate techniques for
pegIFN injections
• Provide information on safe disposal of
needles
PegIFN Administration
• PegIFN alfa-2a[1]
– Premixed vials/prefilled syringes
– Dose is not weight adjusted: 180 μg SQ every wk
– Syringes are overfilled; ensure correct dose before
administration
• PegIFN alfa-2b[2]
– Vials/syringes need to be reconstituted before use
– Redipen
– Weight-adjusted dose: 1.5 μg/kg per dose every wk
• Allow to come to room temperature before use
1. Peginterferon alfa-2a [package insert]. 2010. 2. Peginterferon alfa-2b [package insert]. 2010.
Encouraging Adherence
Adherence to PegIFN/RBV
• Not all patients take al their medication.
–
In one US study 60% were adherent [1]
• 80/80/80 phenomenon
– taking > 80 % of medications correlates with SVR[2,3]
• Remember patients may overestimate
adherence [4]
• For some individuals a multidisciplinary team
may be beneficial for adherence
1. Mitra D, et al. Value Health. 2010;13:479-486. 2. McHutchison JG, et al. Gastroenterology.
2002;123:1061-1069. 3. Raptopoulou M, et al. J Viral Hepat. 2005;12:91-95. 4. Smith SR, et al. Ann
Pharmacother. 2007;41:1116-1123.
Major Predictors of Poor
Adherence to Medication
Patient and
Treatment Factors
•Treatment of asymptomatic
disease
•Presence of psychological
comorbidities, especially
depression
•Patient’s lack of belief in
treatment benefit
•Treatment complexity
•Adverse events of medication
Osterberg L, et al. N Engl J Med. 2005;353:487-497.
Other Factors
• Poor relationship
between the patient and
provider
• Inadequate follow-up or
discharge preparation
• Missed appointments
• Cost of copayment,
medication, or both
Strategies for Improving Adherence to a
Medication Regimen
• Identify risk factors for poor adherence early
– Look for strategies to mitigate some of the factors
• Emphasize value of regimen and potential results to pts
– Some patients are asymptomatic
• Provide simple, clear instructions and simplified regimen
• Encourage the use of medication-dispensing packaging
– Blister packs may be helpful
Osterberg L, et al. N Engl J Med. 2005;353:487-497.
Strategies for Improving Adherence to a
Medication Regimen
• Customize regimen to pt lifestyle when possible
– Injection days – weekend
• Support from family members, friends, and community
• Consider more “forgiving” medications
– Medications with long half-lives, sustained release, or
depot
Managing Adverse Events
PegIFN Adverse Events
AE Occurring in > 20% of
Pts, %
PegIFN alfa-2a/RBV (n =
1035)
PegIFN alfa-2b/RBV (n =
1019)
64/41
67/38
Headache
41
50
Nausea
34
40
Anemia
34
35
Rash
34
29
Neutropenia
31
26
25/20
25/25
Chills
23
39
Injection-site reactions
23
34
22/22
27/21
Dyspnea
22
21
Pyrexia
21
35
Anorexia
21
29
Alopecia
17
23
Fatigue/insomnia
Irritability/depression
Myalgia/arthralgia
Peginterferon alfa-2b [package insert]. 2010.
RBV Adverse Effects
• Adverse events occurring more frequently when
RBV added to pegIFN vs pegIFN alone
– Hemolytic anemia
– Headache
– Cough/SOB
– Gastrointestinal upset
– Rash
– Insomnia
– Teratogenicity
Peginterferon alfa-2b [package insert]. 2010. Peginterferon alfa-2a [package insert]. 2010.
Adverse Event Management
• Anticipate adverse events
– Common and occur in nearly all patients
– Severity and nature of toxicity is highly variable
– If events are not managed well result …Negative impact on
treatment outcome and quality of life
– Adverse event management starts before treatment begins
• Preemptive measures
– Chronic health conditions are stable
– Assess chronic health conditions to ensure they will not be significantly
impacted with treatment side effects
– Provide supportive care during therapy
• During current treatment with pegIFN/RBV[1]
– 10% to 14% of patients discontinue treatment due to adverse
event
• Monitor closely since fatalities can occur
1. Seeff LB, et al. Semin Liver Dis. 2010;30:348-360.
Supportive Therapy for HCV Treatment-Related
Adverse Events
Adverse Event
Potential Interventions
Flulike symptoms (fever, chills, HA, myalgias,
arthralgias, fatigue)
• Acetaminophen (≤ 2 grams/day) *
• Bed rest
• Fluids (noncaffeinated) 8-10 glasses/day
Fatigue
•
•
•
•
Mood changes (depression, suicidal/ homicidal
tendencies, anxiety, irritability)
• Avoid stimulants like caffeine, Ck TSH
• Antidepressants (eg, SSRI), psych referral*
• Short-acting benzodiazepines may help
Insomnia
• Develop good sleep patterns *
• Limit fluid intake/caffeine before bedtime
• Consider sleep aids (eg, diphenhydramine,
trazodone, zolpidem)
Administer IFN at bedtime
Low-impact exercise
Short naps, adjust work schedule
Assess for anemia, TSH..
Supportive Therapy for HCV TreatmentRelated Adverse Events
Adverse Event
Potential Interventions
Nausea/vomiting/anorexia
•
•
•
•
•
Take RBV with food
Eat 6-8 small meals per day
Ginger may help: tea, ale, syrup
Carbonated fluids, jello drinks
Provide prophylactic antiemetics (eg, prochlorperazine)
Diarrhea
•
•
•
•
Drink noncaffeinated fluids
Increase fiber in diet (cereal, toast, rice), BRAT diet
Avoid foods that are spicy, greasy, acidic
Consider antidiarrheals or psyllium
Skin irritation (injection-site
reactions, dry skin, rashes)
• Rotate injection sites
• Take cool baths and use moisturizing soaps
• Consider topical steroid cream or oral antihistamines
Hair loss/thinning
Education, wigs; reversible/temporary as hair grows back
RBV-Induced Anemia
• RBV-induced anemia correlates with achieving
RVR/SVR
– Mean maximum Hb decrease of 2.9-3.1 g/dL in first
6-8 wks[1,2]
– Occurs early within first 1-2 wks and remains low
– Anemia during the first 4-8 wks associated with
improved probability of achieving RVR and/or SVR[3]
– Can worsen fatigue, SOB, CV, quality of life, and lead
to discontinuation of treatment
– Follow product monograph for dose modification
1. Ribavirin tablets [package insert]. 2010. 2. Ribavirin capsules [package insert]. 2010.
3. Sulkowski MS, et al. Gastroenterology. 2010;139:1602-1611.
Managing Hematologic Adverse Events
• Anemia
– Specific thresholds for considering RBV dose
reduction, discontinuation, and/or EPO *
– Note FDA warnings regarding risks associated with
ESAs
• Neutropenia
– Specific thresholds for considering pegIFN dose
reduction, therapy discontinuation, and/or G-CSF*
• Thrombocytopenia
– Specific thresholds for considering pegIFN dose
reduction, therapy discontinuation
See package inserts for details
Laboratory monitoring for
efficacy and treatment toxicity
• Patients on PEG-Interferon combination therapy
should have:
– hematology and blood chemistry testing before the
start of treatment and then periodically thereafter.
– In the clinical trials CBC (including hemoglobin,
neutrophil and platelet counts) and chemistries
(including AST, ALT, bilirubin, and uric acid) were
measured during the treatment period at weeks 2, 4,
8, 12, and then at 6-week intervals or more frequently
if abnormalities developed.
– TSH levels were measured every 12 weeks during
the treatment period.
See package inserts for details
Laboratory monitoring for
efficacy and treatment toxicity
• Genotype non 2,3
– HCV viral load
baseline
– HCV viral load week
12
– HCV RNA week 24 *
– HCV RNA week 48
– HCV RNA week 72
• Genotype non 2,3
– HCV RNA baseline
– HCV RNA week 12
– HCV RNA at the end
of treatment*
– HCV RNA 24 week
after completing
treatment
Laboratory monitoring for
efficacy and treatment toxicity
• Patients on PEG-Interferon combination therapy
should have:
–
–
–
–
–
–
–
–
HCV RNA/VL at baseline
HCV RNA VL at week 12 ( non genotype 2,3)
HCV PCR at week 12 (genotype 2 and 3)
HCV PCR at week 24 ( non genotype 2,3)
HCV PCR at week 24 ( non genotype 2,3)
HCV PCR at week 48( non genotype 2,3)
HCV PCR at week 48( non genotype 2,3)
HCV PCR at week 72 ( non genotype 2,3)
See package inserts for details
Canadian Consensus Guidelines-Management of Hepatitis C , 2007
Canadian Consensus Guidelines-Management of Hepatitis C , 2007
Nursing Role in Patient Education
and HCV Drug Therapy Management
Patient Education
Drug Therapy Management
Anticipated benefits and risks of
treatment
Baseline assessment for
contraindications to therapy
Lifestyle changes
Injection training and/or administration
of injections
Anticipated treatment duration/FU and
need for adherence
Laboratory monitoring for efficacy and
treatment toxicity
Prevention of disease progression
Assessment and evaluation of
•Avoid hepatotoxins—Acetaminophen, adherence
alcohol, herbals, NSAIDs
•Vaccine advocates—hepatitis A and B,
influenza, pneumococcal
Reduce risk of HCV transmission
Management of treatment toxicity
Marino EL, et al. J Manag Care Pharm. 2009;15:147-150.
Smith JP, et al. Am J Health Syst Pharm. 2007;64:632-636.
Success is dependent on
effort and teamwork .