hcv therapy - challenging casess3.gi.org/meetings/wb2015/15acg_vgs_regional_0017.pdf · neeral l....

Neeral L. Shah, MD

HCV Therapy - Challenging Cases

Neeral Shah, M.D.

Associate Professor

Division of GI & Hepatology

Associate Program Director - Internal Medicine

University of Virginia

Learning Objectives

Recognize the changes in HCV therapyDiff ti t di ti f HCV Differentiate newer medications for HCV

Differentiate treatment strategies for cirrhotic vs. non-cirrhotic patients

Understand the risks of missing doses Develop strategies to overcome hurdles in

obtaining medications Be familiar with the current regimens

ACG/VGS/ODSGNA Regional Postgraduate Course - Williamsburg Copyright 2015 American College of Gastroenterology

1

Neeral L. Shah, MD

http://www.hcvguidelines.org

Infectious Disease Society of America (IDSA) and AASLD joint websiteand AASLD – joint website

Full report has good synthesized information Guidelines on AASLD website – less up to date

Pubmed Search

Aug 3, 20151163 articles

Aug 10, 20151241 articles

New articles every week

Hepatitis C AND therapy

Since Jan 1, 2015


2

Neeral L. Shah, MD

Old vs. New Paradigm

Old Paradigm

Many Contraindications!

• Psychiatric Disease• Autoimmune disease• Cirrhosis*• Cirrhosis*• Drug Interactions• Adherence issues


Old Paradigm


• Psychiatric Disease• Autoimmune disease• Cirrhosis*• Cirrhosis*• Drug Interactions• Adherence issues


3

Neeral L. Shah, MD


New Paradigm

• Limited side effects• Shorter duration• No injections• Limited risk of

decompensating

Old Paradigm


• Psychiatric Disease• Autoimmune disease• Cirrhosis* decompensating

cirrhosis (almost none)

• High Cost

• Cirrhosis*• Drug Interactions• Adherence issues

Virology

Virus Entry

Protein Processing

Virus assembly NS5A

Protein ProcessingRNA Replication

Feeney ER, Chung RT, Antiviral Treatment of Hepatitis C. BMJ. 2014 Jul 7;348:g3308

NS5B


4

Neeral L. Shah, MD

Direct Acting Antivirals (DAA)

Serine Protease Inhibitors – “…previrs” NS5A Inhibitors – “…asvirs” (RNA poly) NS5B Inhibitors – “…buvirs”

Feeney ER, Chung RT, Antiviral Treatment of Hepatitis C. BMJ. 2014 Jul 7;348:g3308

Direct Acting Anti-virals

Pawlotsky JM, Hepatitis C Treatment. Gastroenterology, 2015 Mar; 148(3) 468-479.


5

Neeral L. Shah, MD

Case 1 – 53M with jaundice

Known alcohol use, noticed eyes turning yellow Drank ½ pint of vodka per day for 4 years Drank ½ pint of vodka per day for 4 years PMH - Thrombocytopenia in 2012, Diabetes Soc Hx – Abstinent for 6 months PE – jaundice, icteric sclera, firm liver edge, non-

distended, no edema peripherally, no asterixisL b H b 12 1 Plt 100 AST 240 ALT Labs – Hgb – 12.1, Plts – 100, AST – 240, ALT –115, Cr – 1.2, T. Bili – 4.6, INR – 1.3, HCV Viral Load – 2 million IU/mL, HCV Genotype 1, AFP – 31

MELD – 17

Case 1 – Questions that arise

AFP elevation – is there an HCC?D C /GFR k diff ? Does Cr/GFR make a difference?

Has he been treated previously? MELD – 17

A. Treat immediately B. Refer to transplant C. Defer for better therapies D. Treat with PEG-IFN and RBV


6

Neeral L. Shah, MD

ION 1 – May 2014

ION 1 - LED/SOF 12 weeks

LED/SOF 12 weeks had SVR12 of > 95% in treatment naive GT 1 patientstreatment-naive GT 1 patients 865 patients136 (16%) compensated cirrhosis 23 patients with platelets < 90kCirrhotics also achieved SVR12 of 94%Cirrhotics also achieved SVR12 of 94%

LED/SOF safe and well toleratedSide effects – Fatigue, headache, nausea,

diarrhea


7

Neeral L. Shah, MD

TURQUOISE II Study – April 2014

TURQUOISE II

All oral regimen – 3D therapyABT 450/Rit i /O bit i ith D b i ABT-450/Ritonavir/Ombitasvir with Dasabuvir

Exclusively Genotype 1 cirrhosis patients 380 patients – Child Pugh Class A Platelet count as low as 60k Patients with ascites and varices allowed at e ts t asc tes a d a ces a o ed


8

Neeral L. Shah, MD

TURQUOISE II

Compared to telaprevir regimen for superiority and/or non inferiorityand/or non-inferiority

High SVR rates Side effects – Fatigue, headache, nausea,

pruritus

Therapy Regimen SVR Ratese apy eg e S ates

12 weeks 92%

24 weeks 96%

Case 1 – Follow up and Take Home Points

Led/Sof with low dose RBV for 12 weeks G id li h d ith l f D l t i Guidelines changed with approval of Daclatasvir

No studies on decompensated disease Patient tolerated therapy Jaundice cleared, more energy Currently doing well awaiting SVR 12 resultsCu e t y do g e a a t g S esu ts Good options for Genotype 1 disease Minimal side effects make options possible “Genotype 3 is the new 1”


9

Neeral L. Shah, MD

Case 2 – Insurance Changes

57M with chronic HCV disease Previous high risk behavior and ETOH abuse Previous high risk behavior and ETOH abuse Currently abstinent for “many” years PMH – HCV Soc Hx- smoker PE – sclera white, non-distended abdomen, no

id i tspider angiomata Labs – AST – 57, ALT – 74, T. Bili – 1.0, INR – 1.2,

Cr – 0.6, Hgb – 10.3, Plts – 227, HCV viral load – 1 million IU/mL, HCV Genotype - 1

Case 2 – The story…..

June 2015: Approved for Led/Sof – 8 weeksN i h ti ï diNon-cirrhotic naïve disease

Viral Load < 6 million IU/mL - 8 not 12 weeks July 1, 2015: Insurance plan changes will no

longer cover HCV therapy New insurance requires advanced disease or

i h icirrhosis Receive call July 6, 2015 – only 6 pills left What is our next step?


10

Neeral L. Shah, MD

Huffington Post Article – July 2015

"Waiting for cirrhosis to happen to treat HCV is like waiting for cancer to metastasize or forlike waiting for cancer to metastasize or for diabetes to cause complications before treating it. In reality, all cause mortality and per patient per year health care costs are tripled for patients with hepatitis C, whether they have cirrhosis or not."

Dr Douglas Dieterich Mount Sinai Hospital New York CityDr. Douglas Dieterich, Mount Sinai Hospital, New York City

http://www.huffingtonpost.com/lawrence-d-mass-md/-american-health-care-_b_7662210.html

Strategies for Low Stage Disease

Utilize support programs from companiesS t P th L d/S f th Support Path – Led/Sof therapy

ProCeed program – 3D therapy US Elastography Fibroscan, Fibroshear Full time provider to garner prior authorizationu t e p o de to ga e p o aut o at o Pharmacist and nurse and provider team On average takes >10 correspondences


11

Neeral L. Shah, MD

Interruption in Therapy

Drug Half Life

Most product inserts rec. restart therapy ASAPDrug Half Life

Sofosbuvir(GS-331007)

27 hours

Ledipasvir 47 hoursOmbitasvir 21 – 25 hoursParitaprevir 5.5 hours

Ritonavir 4 hours

restart therapy ASAP Take within 12 hours of

prescribed time 3D therapy – cannot

interrupt therapy for more than 7 daysEDasabuvir 5.5 – 6 hours

Daclatasvir 12 – 15 hours

Emergency programs from companies for insured patients

Case 2 – Follow up and Take Home Points

Able to garner an emergency supplyN l i th No lapse in therapy

Recommend patients always keep drug on hand Call when 10 pills left to ensure refills Bring to hospital if admitted Often not on hospital formulary due to cost Counsel if undergoing elective procedures with

potential for complications


12

Neeral L. Shah, MD

Genotype 1,4 – Ledipasvir/Sofosbuvir

Previous Therapy

Fibrosis Viral loadIUs/ml

Treatment Duration Weeks

SVR

Naïve No cirrhosis <6 million Led/Sof 8 97%

No cirrhosis >6 million Led/Sof 12 96%

Cirrhosis NA Led/Sof 12 94%

Treatment Failure

No cirrhosis NA Led/Sof 12 98%

Cirrhosis NA Led/Sof + Riba 12 96%

Cirrhosis NA Led/Sof 24 100%

ION Studies

Genotype 1,4 –Ombitasvir/Paritaprevir/Ritonavir, Dasabuvir

Patient Population Treatment Duration Expected SVR

GT 1a w/o Cirrhosis 3D + Riba 12 weeks 97%

GT 1a + Cirrhosis 3D + Riba 24 weeks 95%

GT 1b w/o Cirrhosis 3D 12 weeks 100%

GT 1b + Cirrhosis 3D + Riba 12 weeks 99%

Turquoise Studies


13

Neeral L. Shah, MD

Genotype 2 – Sofosbuvir + RBV


Naïve Sof/RBV 12 weeks 98%

Treatment Failure Sof/RBV 12 weeks 93%

Treatment Failure Sof/RBV 16 weeks 100%

Naïve + Cirrhosis Sof/RBV 12 weeks 92%

Treatment Failure + Cirrhosis

Sof/RBV 12 weeks 72%

Treatment Failure + Cirrhosis

Sof/RBV 16 weeks 78%

Fission, Fusion, Valence Studies

Genotype 3 – Sofosbuvir + DaclatasvirSofosbuvir + RBV


Naïve Sof + Dac 12 weeks 98%

Treatment Failure Sof + Dac 12 weeks 92%

All Cirrhosis(Naïve and Failures)

Sof + Dac 12 weeks 63%

Naïve Sof + RBV 24 weeks 93%

Treatment Failure Sof + RBV 24 weeks 77%

All Cirrhosis(Naïve and Failures)

Sof + RBV 24 weeks 67%

Ally, Valence Studies


14

Neeral L. Shah, MD

Future Landscape….?

Questions – [email protected]

Thank you.


15

hcv therapy - challenging casess3.gi.org/meetings/wb2015/15acg_vgs_regional_0017.pdf · neeral l....

Documents