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