looking for opinions/expertise on treatment length

[juli4591]

Good morning all - Hub has finished the Incivek - yay!  - and the results of his 12 week blood draws are in.  I want very much to believe what the drs are telling us but I have also been reading here a LOT and need to know what you think.  I appreciate any feedback.  Hub was UND at 4 weeks according to the drs office.  They do their testing with Heptimax.  I do not have the numbers because I didn't have the patient portal set up at that time and didn't get a hard copy.  The 12 wk tests reported <5 reference <5IU/ml  and <.70  < 0.70log IU/ml. Dr said this is UND.

Drs are saying only 24 weeks of treatment needed.  I dearly want this to be true.  What is nagging in the back of my mind is that hub is a relapser from the 48 week SOC with peg/riba, and is stage 3/4. Dr has that listed on her report where she states only 24  total weeks needed.  I've read reports on the 'net and there seems to be so much conflicting information out there.  Maybe the moment of absolute certainty never arrives.

I want to either let my fears go or have a conversation w/dr about this, and wanted to see if anyone else has been in the same position and how long they treated.   I was looking for the poster's log that keeps track of everyone's outcome after treatment and could not find it again - if anyone could lead me to it I would be most grateful.  I am a worrywart by nature and the more info i have the better I feel.  Thanks so much for reading this and giving me your opinions!

[juli4591]

can-do-man, cheflady and idyllic - thanks for your comments and input..  Best wishes to all of you!

[juli4591]

Thanks so much for sharing your experiences, and congratulations on your SVR.  Thanks for the info.  As more time passes, things and treatments changeand its hard to keep up.

[juli4591]

Wow - I am speechless, and so grateful.  THank you, pooh, for spending the time to get all of this together.  I am going to review it all an talk it over with my hub Then we can discuss it intelligently with his drs.  I can't thank you enough for the facts.  You are a lifesaver!

[pooh55811]

I finally found one of the links I was looking for. In this presentation, page 11 shows that cirrhotics with an eRVR who treat for 48 weeks have a 92% chance of SVR whereas those cirrhotics with an eRVR who treat for 24 weeks have a 67% at SVR. That is a huge difference.

http://www.ihlpress.com/pdf%20files/hepdart11_presentations/24_Jacobson_r.pdf

The entire presentation is worth viewing but I wanted to point out that particular page.

[can-do-man]

I would provide the good info pooh gave you to his doctor, I would not want to risk being a eRVR by not doing 48 weeks..... Best to you.

[pooh55811]

Here is the link to Frijole's profile page. Click on the white sheets in her photo section. Those are the spreadsheets with our stats and treatment results.

http://www.medhelp.org/personal_pages/user/223152

[pooh55811]

"Last biopsy right before he treated last time he treated with peg/riba  for 48 weeks dr who talked with us after the procedure said that he was " 3 but teetering on 4". .  That was in 2010. He did the soc right after that.  Dr casually mentioned cirrhosis without ever stating plainly that he had it, but dr who did endoscopy before treatment this time said he saw :very early" cirrhosis. kind of confusing, but I figure if its that close, he does have it and treatment should be  based on that."
--------------------------------

Yes, I would agree with you that if he was Stage 3 teetering on Stage 4 in 2010 and the current endoscopy indicated he has cirrhosis, then he does have it and treatment should be based on that.

Here are more links to articles. You will see they all state that people with cirrhosis should treat for 48 weeks, period, even if the person attained eRVR.


INCIVEK (telaprevir) Fact Sheet

People With Cirrhosis
*Response to Treatment: Undetectable or HCV RNA <1000 IU/mL
at week 4 and/or week 12
*Combination and Treatment Duration: INCIVEK+PEG-IFN+RBV for first 12 weeks, followed by PEG-IFN+RBV only for another 36 weeks.Total 48 weeks

http://www.treatmentactiongroup.org/hcv/factsheets/incivek-telaprevir


While this article does not specifically state the guideline that cirrhotics should do 48 weeks, you will notice that every single patient in the study, all of which were cirrhotics, did 48 weeks of treatment.

http://www.aidsmap.com/Hepatitis-C-patients-with-cirrhosis-respond-well-to-boceprevir-or-telaprevir-with-careful-monitoring/page/2557617/


"Telaprevir: futility rules and treatment durations

.....Treatment durations - .......... all others (prior null responders, prior partial responders, or any cirrhotic patient) should be treated with 12 weeks of triple therapy followed by 36 weeks of peginterferon/ribavirin. "

http://bestpractice.bmj.com/best-practice/monograph/128/treatment/step-by-step.html


In the following link, go down to the Telaprevir chart:

Telaprevir Treatment Duration:  Cirrhosis
Wk 4 RNA     Neg/Pos
Wk 12 RNA     Neg/Pos
Wk 24 RNA     Neg/Pos
Triple therapy: Peg/Rib/Telaprevir     12 wks
Peginterferon/Riba     36 wks
Total Duration Treatment     48 wks    

http://www.anthctoday.org/community/hep/docs/DeterminingTxLength.pdf


The following is a link to an excellent presentation by Dr. Jean-Michel Pawlotsky. It is from 2010 but it is excellent. He is speaking about Resitance Issues in Triple Med. Treatment. The entire presentation is worth watching, but if you don't want to watch all of it, watch slides 32 through 68.

http://74.43.177.57/courses/2010/pg/pawlotsky/player.html


I will keep looking through my bookmarks because I know I have a couple of articles which show the difference in the SVR rates in cirrhotics who treated for 24 weeks and those who treated for 48 weeks. The difference was substantial.

[Idyllic]

"Like so many of the brave posters here you get used to living under the shadow of this disease and for me it colors every big decision we make."
________________

That is so well said. Your words describe exactly how I felt since the day I was diagnosed in 2003. The fact that ten years later this is almost over is literally almost like being born again.

I wish you and yours the best. Please keep us posted♥

[Dee1956]

Hi I started my Incivek tx in Sept 2011.  At that time this was the guideline for someone who had relapsed on previous SOC tx.

In subjects who had relapse after previous treatment to Peg-IFN plus RBV, a response guided regimen is recommended.
• Subjects with undetectable HCV RNA at Weeks 4 and 12 of telaprevir-based treatment receive an additional 12 weeks of Peg-IFN and RBV alone for a total treatment duration of 24 weeks

My doctor also followed the protocol (below) at the time and I did 24 weeks, even though I had been diagnosed as transitioning to cirrhosis.

"patients with cirrhosis who have undetectable HCV RNA (Target Not Detected) at weeks 4 and 12 of INCIVEK combination treatment may benefit from an additional 36 weeks of peginterferon alfa and ribavirin (48 weeks total) "

I am very grateful for my doctor getting me to SVR

I did not know the wording had changed, I appreciate Pooh giving us this information.  

I wish you and your husband the best.
Dee

Frijole has the charts of people who treated, you can go to her home page and see the progress

[cheflady]

Hi not knowledgable like others but well him finishing teleprevir and been und i know from seeing hubby the incivek was diffinately the worse part of his 24wk. Best wishes to you both on rest of tx Jules

[juli4591]

hrsepwrguy, thanks for the coorection.  Pooh, would love to see any information you could find.  Thanks so much.

[juli4591]

This is the information I know about hub's condition.  Last biopsy right before he treated last time he treated with peg/riba  for 48 weeks dr who talked with us after the procedure said that he was " 3 but teetering on 4". .  That was in 2010. He did the soc right after that.  Dr casually mentioned cirrhosis without ever stating plainly that he had it, but dr who did endoscopy before treatment this time said he saw :very early" cirrhosis. kind of confusing, but I figure if its that close, he does have it and treatment should be  based on that.  Sigh.

[pooh55811]

You said your husband has Stage 3/4 fibrosis. Do you mean he has some Stage 3 and some Stage 4 fibrosis, or do you mean he has advanced Stage 3 fibrosis, early Stage 4 fibrosis. This makes a big difference in treatment recommendations. Being late Stage 3/early Stage 4 puts him in the category that would have the best results from treating for 48 weeks. He would have a better chance at SVR if he treats for 48 weeks. 48 weeks is recommended for all Stage 4 patients and many doctors treat Stage 3 with 48 weeks also. Also, if we are Stage 3 on biopsy, we are Stage 3 in the part of the liver that was biopsied, but we could be Stage 4 (cirrhosis) in another part of the liver that was not biopsied.

When the new DAAs first came out the wording for people with Stage 4 fibrosis was different. The recommendations were, "patients with cirrhosis who have undetectable HCV RNA (Target Not Detected) at weeks 4 and 12 of INCIVEK combination treatment may benefit from an additional 36 weeks of peginterferon alfa and ribavirin (48 weeks total) "

But that wording has changed.  The current recommendation is that cirrhotics (Stage 4) treat for 48 weeks regardless of eRVR. The words "may benefit from 48 weeks" have changed to "should treat for 48 weeks."


From: Clinical Care Options

A Practical Guide for the Use of Boceprevir and Telaprevir for the Treatment of Hepatitis C

Selecting a Treatment Regimen: Response-Guided Therapy
Program Directors: Ira M. Jacobson, MD, Jean-Michel Pawlotsky, MD, PhD

Panel Recommendations

•All previous partial or null responders and cirrhotic patients treated with telaprevir should receive a fixed-duration 48-week course of therapy (12 weeks of triple therapy followed by 36 weeks of pegIFN/RBV alone). Tolerability should be followed closely in patients with cirrhosis.

•Some data suggest that patients with stage F3 fibrosis may also benefit from fixed-duration therapy for both boceprevir and telaprevir, and some clinicians may wish to follow the same guidelines used for cirrhotic patients in these individuals with advanced fibrosis.

http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/HCV%20New%20Agents/Module/Practical_Guide/Pages/Page%204.aspx


Also: (when they say "fixed-duration" they mean 48 weeks.)

"The prescribing information for both drugs recommends that both treatment-naive and treatment-experienced patients with cirrhosis should receive a predetermined duration of therapy rather than a response-guided approach. Results from the RESPOND-2 trial comparing response-guided therapy with fixed-duration therapy in treatment-experienced cirrhotic patients support the use of fixed-duration therapy, and response-guided therapy with telaprevir was not evaluated in the REALIZE trial (Figure 5). "

http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/HCV%20New%20Agents/Module/Practical_Guide/Pages/Page%202.aspx


I have bookmarked some other excellent articles concerning this topic and, if I can find them, I will post them. Some contain very good graphs and charts. However, they all recommend 48 weeks of treatment for Stage 4.

[hrsepwrguy]

Sorry I gave you some misinformation, the SVR rate is 94% for eRVR subject treated for 24 wks

In an earlier, dose-finding clinical trial, 78% (52/67) of prior relapsers achieved an eRVR and were treated with 24 weeks of peginterferon alfa and ribavirin (T12/PR24); of those 94% (49/52) achieved an SVR

http://pi.vrtx.com/files/uspi_telaprevir.pdf .

[juli4591]

OMG hrsepwrguy, thanks so much for all of the information, especially your last post. I'd read the information from Vertex but didn't know if  there were studies that contraindicated these statistics.  Your last post about the C216 trial eases my mind.  I'm a little teary because it's hard to believe this might actually work this time. Like so many of the brave posters here you get used to living under the shadow of this disease and for me it colors every big decision we make.  To think that we might truly have a great chance of disposing of that fear is almost more than I can imagine.  Thank you so much for all of the links and information - i truly appreciate it.  

[hrsepwrguy]

Previously Treated Adults Trial C216 (REALIZE)
Trial C216 was a randomized, double-blind, placebo-controlled trial conducted in subjects who did not achieve SVR with prior treatment with Peg- IFN-alfa-2a/RBV or Peg-IFN-alfa-2b/RBV. The trial enrolled prior relapsers (subjects with HCV RNA undetectable at end of treatment with a pegylated interferon-based regimen, but HCV RNA detectable within 24 weeks of treatment follow-up) and prior non-responders (subjects who did not have undetectable HCV RNA levels during or at the end of a prior course of at least 12 weeks of treatment). The nonresponder population included 2 subgroups: prior partial responders (greater than or equal to 2-log10 reduction in HCV RNA at week 12, but not achieving HCV RNA undetectable at end of treatment with peginterferon alfa and ribavirin) and prior null responders (less than 2-log10 reduction in HCV RNA at week 12 of prior treatment with peginterferon alfa and ribavirin).

Among prior relapsers, 76% (218/286) achieved an eRVR and of those 95% (208/218) achieved an SVR.

http://pi.vrtx.com/files/uspi_telaprevir.pdf .

As you can see, your husband has a 95% chance at SVR with 24 wks of tx since he was eRVR

[hrsepwrguy]

Also a result of <5 IU/ml on the heptimax test is UND, congrats to your husband

[hrsepwrguy]

Incivek protocol/treatment duration/futility rules/PCR testing

2.7.1 Duration of Treatment in Treatment-Naive Subjects
In subjects who have had no previous treatment for HCV (treatment-naive), treatment with telaprevir must be initiated in combination with Peg-IFN and RBV and administered for 12 weeks.
• Subjects with undetectable HCV RNA at Weeks 4 and 12 receive an additional 12 weeks of Peg-IFN and RBV alone for a total treatment duration of 24 weeks
• Subjects with detectable HCV RNA at either Weeks 4 or 12 receive an additional 36 weeks of Peg-IFN and RBV alone for a total treatment duration of 48 weeks
HCV-RNA levels should be monitored at Weeks 4 and 12 to determine treatment duration.
Treatment with telaprevir should be discontinued in subjects who do not have an adequate viral response during treatment.

2.7.2 Duration of Treatment—Previously Treated Subjects
In subjects who have had previous treatment for HCV, treatment with telaprevir must be initiated in combination with Peg-IFN and RBV and administered for 12 weeks. Subjects who had a partial response to previous treatment (partial responders) or minimal response
(null responders) to Peg-IFN plus RBV receive an additional 36 weeks of Peg-IFN and RBV treatment alone for a total treatment duration of 48 weeks.
In subjects who had relapse after previous treatment to Peg-IFN plus RBV, a responseguided regimen is recommended.
• Subjects with undetectable HCV RNA at Weeks 4 and 12 of telaprevir-based treatment receive an additional 12 weeks of Peg-IFN and RBV alone for a total treatment duration of 24 weeks
• Subjects with detectable HCV RNA at either Weeks 4 or 12 of telaprevir-based treatment receive an additional 36 weeks of Peg-IFN and RBV alone for a total treatment duration of 48 weeks
Telaprevir must be dosed with Peg-IFN and RBV to prevent treatment failure.

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM252562.pdf

Treatment Futility Rules: All Patients
HCV-RNA  Week 4 or Week 12: Greater than 1000 IU/mL Discontinue INCIVEK and peginterferon alfa and ribavirin (INCIVEK treatment complete at 12 weeks)
Week 24: Detectable Discontinue peginterferon alfa and ribavirin

Laboratory Tests
HCV-RNA levels should be monitored at weeks 4 and 12 and as clinically indicated. Use of a sensitive real-time RT-PCR assay for monitoring HCV-RNA levels during treatment is recommended. The assay should have a lower limit of HCV-RNA quantification equal to or less than 25 IU/mL and a limit of HCV-RNA detection of approximately 10-15 IU/mL. For the purpose of assessing response-guided therapy eligibility, an “undetectable” HCV-RNA result is required; a confirmed “detectable but below limit of quantification” HCV-RNA result should not be considered equivalent to an “undetectable” HCVRNA result.

Treatment-naïve patients with cirrhosis who have undetectable HCV RNA (Target Not Detected) at weeks 4 and 12 of INCIVEK combination treatment may benefit from an additional 36 weeks of peginterferon alfa and ribavirin (48 weeks total)


http://pi.vrtx.com/files/uspi_telaprevir.pdf .

Follow the link for the charts

http://www.medhelp.org/user_photos/list/223152?personal_page_id=4523