TREATMENT OF CHRONIC HEPATITIS C- 2019€¦ · “Treatment of Chronic Hepatitis C” Michael M. Babich, Jr., MD POMA District VIII 32nd Annual Educational Winter Seminar January

“Treatment of Chronic Hepatitis C”Michael M. Babich, Jr., MD

POMA District VIII 32nd Annual Educational Winter SeminarJanuary 31, 2019-February 3, 2019 1

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TREATMENT OF CHRONIC HEPATITIS C-

2019

Michael Babich, MD

Allegheny General Hospital

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Disclosures

• Dr. Babich is on the speaker’s bureau for AbbVie, Inc., Gilead Sciences, Inc., Salix Pharmaceuticals, Inc., and Intercept Pharmaceuticals, Inc. He has stock/ownership in North Shore Endoscopy Center.

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STAGING OF THE DISEASE

• Rationale:• - Insurance coverage• - Assess risk for complications• Methods:• - Liver biopsy• - Imaging tests: • - FibroScan, U/S with Elastography, MRE• - Serologic tests:• - HCV FibroSure, FibroTest (APRI, Fib-4)

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Keys to determining treatment options

- Genotype and subtype

- Viral load (PCR)

- Fibrosis stage (ie. Is cirrhosis present/absent)

- Prior treatment experience (what drugs)

- +/- Presence of resistance mutations

- Consider checking for NS5a RAS’s

- Only officially recommended for genotype 1a pts to receive Zepatier

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HCV LIFE CYCLE AND TREATMENT

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Direct-Acting Antiviral agents (DAA’S)

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DAA Nomenclature

- NS3/4 (protease) inhibitors

- “-previr”

- NS 5a (replication complex) inhibitors

- “-asvir”

- NS 5b (polymerase) inhibitors

- “-buvir”

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FDA-Approved DAA’s

-Sofosbuvir + ribavirin (+/_ Peg-IFN)-Harvoni (sofosbuvir + ledipasvir)(+/- RBV)-Simeprevir + Sofosbuvir-Viekira Pak (paritaprevir + ombitasvir + dasabuvir)(+/-RBV)-Daclatasvir + sofosbuvir (+/- RBV)-Zepatier (elbasvir + grazoprevir) (+/- RBV)-Technivie (paritaprevir + ombitasvir)-Epclusa (sofosbuvir + velpatasvir)-Vosevi (sofosbuvir+velpatasvir+voxilaprevir)-Mavyret (glecaprevir+pibrentasvir)

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Factors common to most DAA’s

• - All-oral

- 8 or 12 weeks: most common durations

- Side effects: fatigue, headache

- 10-20%

- Usu. mild-moderate severity

- N, D, skin change <10%

- <1% rx discontinuation

- Drug-Drug Interactions

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Drug-Drug interactions (DDI’s)

- Refer to each product’s DDI list

- Common contraindications:- St. John’s wort

- “Rif-” antibiotics

- “Old” seizure drugs (ex. Phenobarbital, dilantin, carbamazepine)

- Acid suppression:- PPI’s

- H2RA’s

- OTC antacids

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Common DAA Warnings

-HBV reactivation

-reports of fulminant hepatitis, liver failure, and death

-Amiodarone

-risk of severe symptomatic bradycardia, esp. if on beta

blocker, cardiac comorbidities, or advanced liver dz

-Avoid NS3 (protease) inhibitors in decompensated cirrhosis

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Response to DAA Treatment

• Sustained Viral Response (SVR)

= undetectable HCV PCR 12 weeks after completion of treatment

-durable response in >99% (10 yr F/U)

• SVR approximately 95% in MOST instances

– Higher in naïve, non-cirrhotic, Type 1b

– Lower in Type 3

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“NEXT-GEN” DRUGS

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Vosevi(sofosbuvir+velpatasvir+voxilaprevir)

• 1 tablet daily w/ food x 12 weeks

• Indications:

– Type 1-6, NS5a-experienced

– Type 1a, 3 sofosbuvir-experienced (no NS5a)

• Contraindications:

– GFR<30

– Child B/C cirrhosis

• No role for baseline resistance testing

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Vosevi Trial Data

• POLARIS-1 (Type 1-6, NS5a failures). SVRs:

– GT 1a = 96%

– GT 1 b = 100%

– GT 2 = 100%

– GT 3 = 95%

– GT 4 = 91% (2/22pts, 1 relapse, 1 LT f/u)

– GT 5 = 100% (n=1)

– GT 6 = 100% (n=6)

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Vosevi Trial Data (cont’d)

• POLARIS-4 (Type 1-4, non-NS5a DAA failure). SVR’s (vs SOF/VEL control arm):

– Type 1a = 97% (vs 82%); 1 Vosevi viral failure

– Type 3 = 96% (vs 85%); NO Vosevi virologic failures

– ALL other genotypes- No Vosevi viral failures, 1/125 SOF/VEL viral failure

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Mavyret (glecaprevir+pibrentasvir)

• 3 tablets daily with food

• Safe in ESRD

• Child B - not recommended

• Child C – contraindicated

• No recommendation for baseline resistance testing

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Mavyret- indications/regimens/SVRs

• Treatment-naïve, Type 1-6;– Non-cirrhotic = 8 weeks

– Cirrhotic = 12 weeks

• Treatment-experienced, Peg/RBV/SOF, Type 1,2,4,5,6– As above

– Type 3 = 16 wks

– (For above, approx. 1% viral failure; 4% Type 3 viral failure)

• Treatment-experienced Type 1– NS5a = 16 wks (94% SVR, 1/17 (6%) viral failure)

– NS3/4 = 12 weeks (92% SVR, 0% viral failure)

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THANK YOU

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Documents

TREATMENT OF CHRONIC HEPATITIS C- 2019€¦ · “Treatment of Chronic Hepatitis C” Michael M. Babich, Jr., MD POMA District VIII 32nd Annual Educational Winter Seminar January