Transcript Evaluation of Combination Regimens in GT1 Treatment

HCV: Treat now or Defer
Todd Wills, MD
ETAC Infectious Disease Specialist
Excerpted and adapted from: Seizing the Opportunity:
Optimizing Today’s HCV Therapies,
Exploring Their Role in Tomorrow’s Paradigm – Clinical Care Options Hepatitis
HEPATITIS C TREATMENT EXPANSION INITIATIVE
MULTISITE CONFERENCE CALL
JUNE 19, 2013
Why Treat Chronic Hepatitis C?
• The disease
– Common, chronic, and potentially progressive
– Complications are becoming more common[1,2]
• Liver failure, HCC
• The treatment
– Viral cure, or SVR, is achievable
– SVR associated with histologic improvement and gradual
regression of fibrosis[3]
– SVR reduces risk for liver failure and HCC, improves
survival[4,5]
1. Kanwal F, et al. Gastroenterology. 2011;140:1182-1188. 2. Shaw JJ, et al. Expert Rev Gastroenterol
Hepatol. 2011;5:365-370. 3. Poynard T, et al. Gastroenterology. 2002;122:1303-1313. 4. Craxi A, et al.
Clin Liver Dis. 2005;9:329-346. 5. Shiratori Y, et al. Ann Intern Med. 2005;142:105-114.
We Understand the Rules of the
Game With IFN-Based Treatment
• Establishing patient candidacy
• Assessing potential drug–drug interactions
• Evaluating likelihood of SVR in treatmentnaive and treatment-experienced patients
• Applying response-guided treatment
algorithms to maximize response and mitigate
treatment failure
• Optimally managing adverse events
For Genotype 2 or 3, PegIFN/RBV
Remains Standard of Care
• Highly effective therapy with higher cure rates
than genotype 1
• 24 wks of therapy is recommended[1,2]
– Some patients (with RVR and low baseline HCV
RNA) may be treated for 16 wks if therapy poorly
tolerated, although relapse rates may be higher[2]
• Future regimens may offer further
improvements
1. Ghany MG, et al. Hepatology. 2011;54:1433-1444. 2. EASL. J Hepatol. 2011;55:245-264.
Rationale for Prompt Treatment of
HCV
• HCV is a progressive disease, associated with persistence of
viral replication and ongoing necroinflammation and fibrosis
• Remission (SVR) is associated with loss of active viral
replication and improvement in hepatic fibrosis
• Important questions
– Does that equate to a need to treat all patients?
– Can we avoid losing time for patients destined to progress?
– How do we avoid unnecessary or detrimental treatment
when there are improved treatments pending?
Indications for Treatment of Chronic
HCV Infection
• All patients, regardless of the degree of fibrosis, are
potential candidates for treatment
• Patients with mild disease may not require
immediate treatment
• For those who require treatment
– Patients should be fit for the regimen
– Patients should have the ability to adhere to
treatment goals and monitoring
Who Should Be Treated Now?
Pts Who Want Tx
Want to be cured of
disease
Personal or social
reasons
Pts Who Are
Eligible for Tx
 Eligible for pegIFN/
RBV
 Fit for regimen
Pts Who Are
Motivated and
Understand . . .
Likelihood of response
Plans for pregnancy
 No contraindications
Risks/benefits of
treatment
Social support
 Disease stage
Risk of resistance
Eligible for
reimbursement now
Possibility of shortened
therapy
What is “coming down
the line” for their
genotype
Severity of Disease Increases Need for HCV
Therapy but Also Impairs Response
 May not need immediate
treatment
 BUT
 Easier to treat
 High likelihood of
response
Mild disease
 Greater need for treatment
 BUT
 Response may be impaired
 Perhaps more effective options in
future, but efficacy of some
investigational agents may be unclear
due to trial eligibility criteria
Advanced disease/
cirrhosis
What Are My Chances of Being
Cured With Current Therapy?
 Black
 Cirrhosis
 Genotype 1
(1a worse than 1b)
 IFN
nonresponsive
 IL28B TT
Less favorable
prognostic factors




White
No fibrosis
Genotype 2/3
IFN responsive (eg,
RVR/EVR or response
to lead-in)
 Previous relapser
 IL28B CC
Favorable
prognostic factors
Limitations of Current Regimens
and Prospects for Future Regimens
Current
Future
•Must be eligible for pegIFN/
RBV
•Large pill burden, TID dosing
of PIs (at present); parenteral
IFN
•Challenging adverse events
•High likelihood of resistance
with treatment failure
•Current PIs only effective for
genotype 1
•Possibility of resistance with
poor adherence
•Perhaps IFN free
•Lower pill burden, less than
TID dosing; perhaps all oral
•May be better tolerated
•May not generate resistance
•Pangenotypic or at least more
•Higher barrier to resistance
with some classes
Challenging Patients for Whom Treatment
With Current Options Less Than Optimal
• Cirrhosis (all genotypes)
• Decompensated cirrhosis
• Null responders
• Pretransplantation
• Posttransplantation
• Renal failure
– Impaired renal function
– Dialysis
– Renal transplantation
recipients
• Injection-drug users
– Methadone substitution
• Thalassemics
• Children
• IFN contraindicated
• IFN intolerant
• Those on “edge” of society
• Psychiatric comorbidity
The Need to Cure Cirrhosis: Survival in
Patients With HCV and Cirrhosis
Survival Probability
Compensated
100
After first major
complication
Patients (%)
80
60
40
20
0
0
12
24
36
48
60 72
Mos
Pts at Risk, n 384 376 342 288 236 165 126
65 39 21 11
7
4
4
Fattovich G, et al. Gastroenterology. 1997;112:463-472.
84
96
79
3
52
3
108 120
39
2
25
1
The First-Generation Protease
Inhibitors: Where Are We Now?
• Telaprevir and boceprevir are harbingers of important
treatment advance
• Improved SVR rates in both naive and experienced patients
• Certain patients (advanced disease) require therapy
imminently and should be treated now
• Others may be motivated to be treated now—opportunities
for cure, candidates for shortened therapy, and/or personal
reasons
• For many, the choice is not clear
• The advent of triple therapy changes the way treatment
discussed with patients
– Clinicians must educate and advocate for patients to
choose the correct course of treatment