HCV: Treat now or Defer
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Transcript of HCV: Treat now or Defer
HCV: Treat now or Defer
Todd Wills, MDETAC Infectious Disease Specialist
HEPATITIS C TREATMENT EXPANSION INITIATIVEMULTISITE CONFERENCE CALL
JUNE 19, 2013
Excerpted and adapted from: Seizing the Opportunity: Optimizing Today’s HCV Therapies, Exploring Their Role in Tomorrow’s Paradigm – Clinical Care Options - Hepatitis
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 treatment-
naive 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
Pts Who Want TxWant to be cured of disease
Personal or social reasons
Plans for pregnancy
Social support
Eligible for reimbursement now
Pts Who Are Eligible for Tx
Eligible for pegIFN/ RBV
Fit for regimen
No contraindications
Disease stage
Pts Who Are Motivated and Understand . . .
Likelihood of response
Risks/benefits of treatment
Risk of resistance
Possibility of shortened therapy
What is “coming down the line” for their genotype
Who Should Be Treated Now?
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
Advanced disease/ cirrhosis
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
What Are My Chances of Being Cured With Current Therapy?
Black Cirrhosis Genotype 1
(1a worse than 1b) IFN nonresponsive IL28B TT
Favorable prognostic factors
Less favorable prognostic factors
White No fibrosis Genotype 2/3 IFN responsive (eg,
RVR/EVR or response to lead-in)
Previous relapser IL28B CC
Limitations of Current Regimens and Prospects for Future RegimensCurrent•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
Future•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
Fattovich G, et al. Gastroenterology. 1997;112:463-472.
Compensated
After first major complication
Survival Probability
100
Pat
ien
ts (
%)
80
60
40
20
01200 12 24 36 48 60 72 84 96 108
Mos
384 65
Pts at Risk, n 376 39
34221
28811
2367
1654
1264
793
523
392
251
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