liver institute of virginia education, research and treatment for patients with liver disease iver...
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Liver Institute of VirginiaEducation, Research and Treatment for Patients with Liver Disease
IVerBon SecoursHealth System
WHY CHOOSE TELAPREVIR
Mitchell L Shiffman, MDLiver Institute of Virginia
Bon Secours Health SystemRichmond and Newport News, VA, USA
IVer
TELAPREVIRTREATMENT NAÏVE AND RELAPSE
HCV RNA UD UD UD
RVRTelaprevir
PEGINF
Ribavirin
PEGINF
Ribavirin
No
RVRPEGINF-RBV
Log HCV < 3 < 3 UD
Stop Rule >3 >3 +
Week 4 8 12 16 20 24 28 32 36 40 44 48
ML Shiffman, R EstabanLiver Intl 2012; 32 (suppl 1):54-60.
IVer
TELAPREVIRNON-RESPONSE AND CIRRHOSIS
RVR
HCV RNA
Telaprevir
PEGINF
RibavirinNo
RVRPEGINF-RBV
Log HCV < 3 < 3 UD
Stop Rule >3 >3 +
Week 4 8 12 16 20 24 28 32 36 40 44 48
ML Shiffman, R EstabanLiver Intl 2012; 32 (suppl 1):54-60.
IVer
SVR RATESVERY COMPARABLE
Boceprevir Telaprevir
Treatment Naïve:
eRVR
Delayed response
% with eRVR
96%
66-75%
56%
89-92%
64%
58-60%
Retreatment:
Relapse
Partial response
Null response
INF sensitive (lead-in)
INF insensitive (lead-in)
69-75%
40-52%
NA
73-79%
33-34%
84-88%
56-61%
31-33%
NA
NA
IVer
SVR RATESVERY COMPARABLE
Boceprevir Telaprevir
Treatment Naïve:
eRVR
Delayed response
% with eRVR
96%
66-75%
56%
89-92%
64%
58-60%
Retreatment:
Relapse
Partial response
Null response
INF sensitive (lead-in)
INF insensitive (lead-in)
69-75%
40-52%
NA
73-79%
33-34%
84-88%
56-61%
31-33%
NA
NA
IVer
SVR RATESVERY COMPARABLE
Boceprevir Telaprevir
Treatment Naïve:
eRVR
Delayed response
% with eRVR
96%
66-75%
56%
89-92%
64%
58-60%
Retreatment:
Relapse
Partial response
Null response
INF sensitive (lead-in)
INF insensitive (lead-in)
69-75%
40-52%
NA
73-79%
33-34%
84-88%
56-61%
31-33%
NA
NA
IVer
TELAPREVIRWHY CHOOSE THIS REGIMEN?
It is just an easier treatment regimen
IVer
TELAPREVIRITS JUST EASIER
• All three medications are started at the same time• All patients get 12 weeks of telaprevir
• Treatment naïve• Prior relapse• Prior non-response• Cirrhosis
IVer
TELAPREVIRITS JUST EASIER
• If you have to stop telaprevir at week 8 for adverse events the SVR is only marginally reduced.
50% 54%
TelaprevirPEGIFN-2a
RibavirinIf NO eRVR:
PEGINF + Ribavirin
If eRVR:PEGINF + Ribavirin
TelaprevirPEGIFN-2a
Ribavirin
128
83% 89%
Week of TPV
12 4824Weeks0 8
IM Jacobson et al.N Engl J Med 2011; 364:2405-16.
IVer
TELAPREVIRITS JUST EASIER
• Only 2 treatment durations• Treatment naïve and prior relapsers:
• 24 weeks if achieve extended rapid response• 48 weeks with delayed response
• Prior non-response and cirrhosis• 48 weeks
IVer
TELAPREVIRITS JUST EASIER
• 60% achieve eRVR. Treated for 24 weeks
• 21% have delayed response. Treated 48 weeks.
• 81% of patients become HCV RNA undetectable during treatment
0
20
40
60
80
100
% H
CV
RN
A (
-)
IVer
TELAPREVIRITS JUST EASIER
• Smaller pill burden• 2 capsules TID = 6/day• Randomized controlled trial
suggests telaprevir can be dosed 3 capsules BID without impacting SVR
=
P Marcellin et al.Gastroenterol 2011; 140:459-468.
IVer
TELAPREVIRITS JUST EASIER
0
1
2
3
4
5
6
7
-4 0 4 8 12 16
WEEKS
HC
V R
NA
(IU
/ml)
• Stop rules at weeks 4 and 12.
• Allows resistant virus to be recognized earlier.
• Resistance monitoring uses the same cutt-off.
• Week 4 >Log 3
• Week 12 >Log
• Week 24 negative
IVer
TELAPREVIRNEGATIVE FEATURES
• Side effects of therapy
• Side effects of peginterferon and ribavirin
• Side effects of telaprevir
• Anemia
• Rash
• GI symptoms
IVer
RASHUNIQUE TO TELAPREVIR
• Appears in over half of patients treated with telaprevir• Typically appears during first 4 weeks of treatment• Worsens progressively during treatment• Most patients never reach stage 3-4• If severe, can stop telaprevir a few weeks early• The decline in SVR is minimal even in patients with
delayed virologic response
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TELAPREVIRGRADE 2 RASH
IVer
TELAPREVIRGRADE 3 RASH
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TELAPREVIRGRADE 4 RASH
IVer
TELAPREVIRSIDE EFFCTS
• GI toxicity:• Nausea• Vomiting• Diarrhea• Anal-rectal burning
IVer
TELAPREVIRSUMMARY
To treat HCV with Incevik
Is not a trick.
Just start it with PEG and Riba together.
Treat for 12 weeks and see it get better.
If negative at week 4.
Its virtually a cure.
Continue PEG and riba for sure.
Till week 24.
And then dash straight through the door.
IVer
TELAPREVIRSUMMARY
However,
If the response is delayed.
Do not be dismayed.
For if less than a thousand by month 3.
A cure can still be.
Adhere to the stop rules at 4 and 12 weeks.
This is important and so do not cheat.
And you will see.
This rule will keep you mutant free.
IVer
TELAPREVIRSUMMARY
AEs include rash, anemia and a sore bum.
This is not fun.
This make patients glum.
And their physicians run.
And so my friends,When treating with telaprevir there is no reason to quiver.Because its dam good at getting HCVOut of the liver.