Definition of RVR on victrelis and tx duration

Question

Hi - I am struggling to clarify my recommended tx duration on triple therapy with victrelis. I am in week 28 of tx. Grateful for your insights! 
I was a null responder to previous tx with peg/RIBA. Am also TT genotype. Possibly f3 fibrosis but no cirrhosis.
I started triple therapy with the 4 week lead-in phase in July 2012. At the end of lead-in (week 4) I was still detected, achieving less than 1 log drop in virus load. I added the victrelis and my PCR test at week 8 came back undetected. Yippee! Also undetected at week 12 and week 24. Yippee! 
Now I am deeply engaged in the question of how long will / should my tx be.
My reading of the literature suggests that I cannot be defined as RVR and therefore eligible for 36 weeks tx instead of 44, because I was still detected at week 4, and also my previous status as a null responder suggests i should be doing the full 44 weeks. 
I think my Gastro and I sometimes talk at odds because of definition issues, eg RVR. Is the 4 week lead in phase considered week 4 of tx when you are on victrelis? Does it matter if you achieve undetected at week 8 if you are a previous null responder? 
Has anyone else' grappled with these questions?

Cat3572 · Answer

Replying to your good self and 2ndtimearound - huge congrats on 4 week UND - very good news. I had to do the whole 48 weeks, but I have to say it was worth it! SVR at 6 months post tx, and still feeling good at 12 months now. Horrible sides throughout - severe neutropenia and bad taste effects, and I didn't think I could stomach the 8 hourly pill regime for long, but managed it.
Good luck to both of you with your next stage of tx - you are on the home run, really! :-)

Studio58 · Answer

I am on the same treatment.  Genotype 1a, CC gene and went Und at the end of the 4 week lead in.  They originally told me 48 weeks but they now say maybe 36 weeks due to my RVR.  They won't have any more to say until week 24 which is still a way off as I start week 11 tomorrow. It is a grind that's for sure.

2ndtimearound7744 · Answer

I am in the same boat.. I have been Non Detected since 8 weeks. 4 weeks lead in then adding Victrelis, however I am Geno type 1A and was treated before with just peg/ribo. I saw the specialist in June and the nurses and him were discussing my end date. I believe when I asked him how much longer he said "When I am done Victrellis I am done everything... Nurse has it figured out 36 weeks from start date.... I am thinking 36 weeks from start of Victrelis. I don't want to stop short either and have it come back so on the phone on Monday to have this clarified

Cat3572 · Answer

Just a quick update - my gastro has now agreed that I should be doing 48 weeks. I am relieved to have the duration question cleared up. Now I am girding my loins to get through it! Thank you once again for your assistance.

Cat3572 · Answer

This is all so very helpful thank you - I now feel armed with sufficient information to have the discussion with my gastro!

Idyllic · Answer

Thought you might be interested seeing a thread by a person who was in a similar position with a doctor who had differing notions of how long to treat with Victrelis. He is a different Genotype but it is the 'less than one log drop rule after the four week lead in.' This is actually when I learned it myself

http://www.medhelp.org/posts/Hepatitis-C/VICTRELIS-QUESTION/show/1787312#post_8224110

Idyllic · Answer

Your doctor's understanding of the definition of RVR is right but not how it applies to Boceprevir in this case. RVR only means HCV RNA negative after 4 weeks of therapy. You will still detected and had less than a one log drop. That means Interferon Resistant. 

If you read the chart in that one link it says that RGT rule takes precedence over that. RGT stands for Response Guided Therapy the Boceprevir (Victrelis).

That chart explains you were eRVR HCV RNA negative at week 8 but for BOC therapy: RGT criterion applies - meaning that less than one log drop rule kicks in and you treat the whole 48.

You might want to print one of those and show your doctor that treatment duration for triple therapy is based on your response to the meds, i.e., response guided therapy.

pooh55811 · Answer

I think you will find that even though you were UND at week 8, the fact that you are a TT and a previous Null Responder is going to trump your UND at week 8. Plus, you had <1 log drop at week 4 (end of lead in). So being UND at week 8 is nice, but it is not the most important or the determining factor in your situation. 

After you read the results of the trials you will see that having a <1 log drop at week 4, being a TT, and being a prior Null Responder all chip away at your chances for SVR. The recommended Tx in your situation is 48 weeks (4 weeks lead-in plus 44 weeks triple) so I am not sure why your doctor is pushing for a shorter than recommended treatment time. 

In the Clinical Care Options summary you can see that the results were as follows:

If a person had < 1 log10 decline at week 4 

The Response-Guided Boceprevir + PegIFN/RBV treatment resulted in 24% SVR rate. (shorter than 48 weeks)

The 48-Wk Boceprevir + PegIFN/RBV  treatment resulted in 40% SVR rate.

That is a significant difference in SVR rates.

Cat3572 · Answer

Thank you both! I can see a couple of links in your suggestions that I have not read yet so I will dive in. But so far, you are both reading my situation the way I do. On the other hand, my Gastro has suggested (1) finishing tx at 36 weeks because I am 'RVR' according to him,  or (2) finishing bocep at 36 weeks and then doing the final 8 weeks on peg/RIBA only. I cannot find any data to support either scenario given my situation, so I will be pressing him again to justify his recommendation. Much as I would LOVE to finish early (i have had and continue to have an extremely difficult time on triple), I am extremely concerned that after all this, I give myself the best chance at SVR. 
Thanks again, and i will post as i find out more from the Gastro.

pooh55811 · Answer

Yes, but we gave different links so hopefully we covered everything.

pooh55811 · Answer

Here is a link to the results of trials:

http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/Berlin%202011/From%20Podium%20to%20Practice/Capsules/12.aspx?lg=print

"Among treatment-experienced patients with IL28B TT genotype, trend toward lower SVR rates in patients who received response-guided boceprevir-based therapy vs 48-week boceprevir-based therapy"

So even if you were UND at 8 weeks your chance for SVR is better if you do 48 weeks instead of a shortened response quided treatment.


You may have to register to view this article but it is free and very well worth registering to read it (and other articles they have).

Idyllic · Answer

Oopsy Sorry Pooh ~ looks like we were responding at the same time :)

Idyllic · Answer

I am thinking 48 weeks. UND at eight weeks but detectable at 4 weeks with less than one log drop after the lead in.

This link says (see chart for BOC =- Boceprevir)
eRVR = HCV RNA negative (LLD not LLQ) between week 8 and week 24 of BOC therapy: RGT criterion for BOC

RGT means Response Guided Therapy 
http://www.flyingpublisher.com/0011_04.php

Here is Boceprevir "Response Guided Therapy" chart:
http://www.medhelp.org/user_photos/show/284656?personal_page_id=1282072

It says:

OR patients who were prior null responders (<2 log viral load drop at 12 weeks) OR patients, who after 4-week peginterferon/ribavirin lead-in have less than ONE log virus drop (i.e., are interferon-resistant) should be treated with 4 + 44 (4-week lead-in with peginterferon/ribavirin followed by peginterferon/ribavirin/boceprevir for 44 weeks, for a total of 48 weeks of therapy). 
_______________

Here is a link:
http://bestpractice.bmj.com/best-practice/monograph/128/treatment/step-by-step.html

_______________________

pooh55811 · Answer

"I am struggling to clarify my recommended tx duration on triple therapy with victrelis. ..... I was a null responder to previous tx with peg/RIBA. Am also TT genotype. Possibly f3 fibrosis but no cirrhosis. "
------------------------------------

If you are a previous null responder, then the guidelines state that you would treat for a total of 48 weeks ... 4 week Inf-Riba lead in, plus 44 weeks of Inf., Riba, and Beoceprevir. 


"Does it matter if you achieve undetected at week 8 if you are a previous null responder? "
-----------------------------------

No. Because you were a previous null responder, you would treat for 48 weeks total. 


I cannot copy and paste this info but here is the link. Go down to Boceprevir. Go down to the last "box" and look under  Poorly INF- responsive popuilations. It says they did not do studies on previous null responders in the Bocep trials but if one was a prev. null-resp. and one is now treating with Bocep then do the 4 week lead in and an additional 44 weeks (total 48 weeks).  

http://hepatitiscnewdrugresearch.com/pocket-guide-telaprevirboceprevir.html