Null Responder?

[slideman]

I was refered to this site from another hep-c site and I hope to find some answers here. I am in my 14th wk of triple therapy. I was diagnosed in 2001, and began tx right away. It was 3 shots a week then, the old short acting int. 3 months later the new long lasting int became available and I switched to that. My vl was not checked until 24 wks into tx and there was still virus present. 7 months later still virus, so the Dr. at the time put me on 2 injections at a time. That Dr is now deceased and this has become an issue too. Anyway, the records indicate after 3 months later I stopped tx because I thought I would surely die. Then 3 wks later my vl test showed und.(It took that long to get results then) So back on int I went, but the virus had become detectable again. They wanted me to go another 9 months on tx and I knew I couldnt do it. Going into tx I weighed 230lbs and worked construction. Coming out, 185 and bankrupt!!
So I watched and waited for the new triple therapy to become available. Incivek was chosen and away I went. Of course I heard all the success stories and believed them. @ 4 wks I was und, then again @ 12 wks. The test was done by the lab at Mayo, they said it is <1. I was elated!! However now today I hear that I am going to be considered a null responder based on the data from 10 years ago. Is this correct? That would indicate I need 48 wks of tx and only have a 30% chance of SVR? Is that worth the risk? What if I dont get SVR and am then classified null on the triple tx?
I am very disapointed and considering stopping tx, although the sides are way better now that I have made the Incivek hurdle.  My biopsy score before treatment were 1.5 and 2.  Ten years ago it was 2 and 2.  
Any feedback will help. I got a hold of the Dr. @ University of Cincinnatti who ran the phse 3 Illuminate. He made it sound like if there was no vl test @ 12 wks 10 yrs ago then Null was not correct as far as incivek was concerned. I dont know. I am very tired of never knowing what the hell the truth is so I have decided to become proactive and work on this myself. Thanks ahead of time for all your efforts to help everybody that suffers with this devil.

[susan400]

If they don't stop you, then, continue the course of triple, is my advice.  And even if they do stop you, if you've already reached undetected, then, perhaps your regular GI/hepatologist could roll you over onto regular SOC for 24 wks (if you're still undetected at 24 wks-after the early triple and the rolloever SOC), then, I'd say, you should be able to stop (if your regular doctor agreed).  It's really hard to find trials, or doctors to retreat you if you've been exposed to the Telaprevir and then, don't get SVR.  So, don't stop if you can continue...   That's my advice.  Susan400

[Trish77]

Well, your last treatment was a helluva mess for a variety of reasons wasn't it.  Good on you to pull yourself up and out of all that.  All the more reason to NOT fixate on that 30% SVR rate, you have no idea if that applies to you anymore than you know if you were a non or a null responder.  

Your docs don't have nearly enough information to be able to safely call it that your treatment can stop at 24 weeks and they don't want to mess with resistance issues, is my guess. I have to say I agree with them.  When you read the literature on preventing resistance, one of the strategies is to achieve SVR.  I think that's what your docs are after and giving you the best chance they can to achieve that.

Fixate instead on your 4 week UND - everyone's golden ticket - and your tolerable side effects and ride it out.  This could very well be sayonara to this virus for you and it's looking good.  Good luck.

Trish

[meakea]

You've gotten some good information here but it looks like you have a lingering question about the odds of triple tx working for you.  I'm not a numbers person but it would seem to me that since you kicked a** on your VL so that you were UND by week 4 you already are ahead of the game.  Being UND by week 4 would, in my opinion, put your odds up higher than 30% but, again, I'm not a numbers person.  I can only tell you from my own treatment experience with SOC (not triple therapy) that I was UND by week 4 (geno 1b) and it sent my odds of being successful sky high and it was correct because I am currently SVR.  When I started treatment my odds probably weren't much better than your doctor stated yours is, but the clearing by week 4 changed all that.

It doesn't sound to me like you are concerned about the 24 weeks vs 48 weeks so much as the percentages...right?  You're in the game for 48 weeks as long as your odds are greater??....is that what you're saying?

[Willy50]

Yes, I agree and posted a second time to amend what I wrote.  I think I was correct in the first post about the OP not being a null responder.

If there was never a PCR until after week 24 I'm not certain that the "null responder" tag applied.  

I've been looking for data that correlates SVR rate(w/ triple therapy) and eRVR, and staging, I know it improves the odds of the OP but I can't put my hands on it this AM.  Regardless.....

The guidelines are the guidelines; 12 & 36.

Willy

[can-do-man]

Your taking alot for granted since he did not have a pcr at week 12. How would one know if he had a 2 log drop at that time?

What is known is for some reason he was left on tx after 24 weeks and still not und. The guidelines are clear whether Null or partial 48 weeks is what they call for. Being one had a eRVR that greatly improves your odds for SVR, IMO taking a shortcut now would be a huge risk.

[willbb]

Good news you are not doing street drugs as this would certainly be counter-produtive to a good chance of success this time,and also the fact  you don"t seem to need an AD  is positive, as thses sometimes have side effects in their own right.
I would agree with the above  in that your  previous response is somewhat a grey  area as to definition .the bottom line is you have the eRVR this time which means a very good chance of success(more than likely better than the documented 32%for nulls),and just the fact you failed twice previously ..personally I would do the 48 as the doctor seems to advise ,in order for the best possible outcome.
A failed response this time  could mean  resistance issues and possibly an inability to treat again for a number of years.

Best to you..
Will

[Willy50]

I awoke and re-read what I wrote.  I was quibbling about the definition of "null responder", a term I'm not certain applies here.

http://onlinelibrary.wiley.com/doi/10.1002/hep.24641/full

"Three categories have been defined for persons who had received previous therapy for CHC but who had failed the treatment. Null responders are persons whose HCV RNA level did not decline by at least 2 log IU/mL at treatment week 12; partial responders are persons whose HCV RNA level dropped by at least 2 log IU/mL at treatment week 12 but in whom HCV RNA was still detected at treatment week 24;"

So, we can at least agree that you were a partial responder.  The guideline that Vertex provides indicate 12 weeks triple therapy followed by 36 weeks of SOC.  
http://pi.vrtx.com/files/uspi_telaprevir.pdf  (page 2)

It looks to me as though you may fit into a different response curve now, but there are no guidelines for that established, and so....the doctor is correct about the treating time, possibly incorrect about the null response handle.

Given that you may be considered a partial responder, and given your eRVR this time your odds look pretty good to me.

willy

[slideman]

I was on riba 10yrs ago, same dose as now. I think I can go the 48 wks, but I really need to know I have a fighting chance and 30% is not a good one. I have 2 cousins that cleared 10 yrs ago, dont know why I didnt accept the fact that I was not diligent with my treatment. I did lots of street drugs while on treatment, mailny Cocain. Tx made me a raging nut job. I tried the antidepresents and they made me sick this time. Way worse than triple therapy did. Last time they started me on everything at once and it was bad. I am not takeing anything for depression this time and dont think I need to. Also I havent done any street drugs since tx 10 yrs ago!! And dont miss any of it. I think tx triggered all kinds of goofy things I did when I was in my 20's.

[Trish77]

I don't suppose you had a viral load test done before the 4 week one?  Wishful thinking and not required, but thought I'd ask.

Under current treatment guidelines, you would have stopped treatment at 24 weeks with detectable virus in your blood at 24 weeks.  Since you weren't tested at any time before then, it's impossible to say if you responded at some point, how well and if you actually relapsed or had a null response.  There's also little information on the dosages throughout that 24 weeks til the detectable test to determine if other factors might have contributed to your detectable test at 24 weeks.

You've already done the 12 weeks of Incivek and had the fantastic response of UND at 4 weeks.  Congratulations!  That's good news.  I'd say for the purposes of achieving SVR your doctors want to treat you as a null responder but that doesn't mean the 30% chance of success applies to you.  I wouldn't focus on that so much.  I would look at your 4 week UND.  The issue you have now though is a current one with triple therapy and that's resistance.  In your shoes with the issues you've had previously of having a hard time of clearing the virus and the possibility of developing resistance to this class of PI if you don't clear, I think it would be prudent to go the 48 weeks.  It may not be what you want to hear but I don't think you want to have to come back for a third round - and you'd be looking at the wild card of resistance issues on top of it.  I think you have a very hopeful chance of clearing with a 4 week UND by going 48 weeks and in your shoes, with your history, that's what I would do.  You've got the triple part past you and with sides "way better" .. I'd hang in there and keep on truckin'.  I'd say it's looking pretty hopeful at this point.  

Good luck to you.

Trish

[Willy50]

No..... I'm not sure it is correct, and I think they should double check it with someone else, or you can also check it w/ a Vertex 24/7 nurse.

Most null responders don't even clear, so the past data seems a little confusing.  Hard to say if the PCR was dead on.

Part of what matters is THIS time; you had a good response rate.  Frankly, it is one good reason to do a lead in as they do w/ Victrellis/ boceprevir; you would have a very good sense of your response rate w/ a lead in.  I've seen a few people who responded quite differently on a new TX.  One pulled an RVR that never happened before and another past failure became UND during a lead in, before they even started the PI.  

My point is that things change and one of the best predictors I am aware of is ones response rate.  I'm wondering in the accuracy of a 10 year ago Tx should carry much weight.  You didn't mention your riba dosing then, if there were reductions, etc.

As it sits the hardest part of TX may be over; the triple therapy portion.  Your odds are very good with you response rate.  The person who wants you to do an extra 24 weeks is looking for certainty and increased SVR rate for you, but I'm not sure that an extra 24 weeks is merited in your situation.

willy

[HectorSF]

The past facts sound very "ify" at best. What matters is how you are responding to treatment now. Since you achieved eRVR that shows that you respond to interferon and ribavirin. That is what matters.

From the data you mention it is impossible to tell if you were a null responder or a partial responder. SVR is 59% for partial responders that treat with INCIVEK for 48 weeks. (from REALIZE study).
"The prescribing information recommends that all previous partial or null responders receive 12 weeks of triple therapy followed by 36 weeks of pegIFN/RBV."

The guidelines are clear ...unless you are treatment naive or a previous relapser (neither of which you are) you should treat for 48 weeks for the best chance of SVR.

"Response-guided therapy is recommended when using telaprevir-based triple therapy for treatment-naive patients and previous relapsers. All patients should receive 12 weeks of triple therapy, followed by a period of pegIFN/RBV alone. The duration of pegIFN/RBV is based on achievement of undetectable HCV RNA at both Week 4 and Week 12. Patients who meet this criterion should receive a total of 24 weeks of therapy (12 weeks of triple therapy followed by 12 weeks of pegIFN/RBV alone), and patients who do not should receive a total of 48 weeks of therapy (12 weeks of triple therapy followed by 36 weeks of pegIFN/RBV alone). "

You are in a good position. You have little liver damage. You are responding to treatment. You have mild side effects. I am sorry if is not the answer you want to here but you should have been told you would need to treat for 48 weeks BEFORE you stated treatment. You doc knew you were not treatment naive and you were not a relapser.

More info about people that have failed treatment previously...

"Impact of Previous Treatment Response and Fibrosis Stage
The expert panel notes that categorizing previous response to therapy may be a challenge in the clinic owing to a lack of detailed records, standardized definitions of response, lack of patient evaluation at key time points on previous therapy, and potential lapses in patient memory. Identifying a previous relapse tends to be less of a challenge, whereas differentiating a previous partial response from null response can be difficult or imprecise. Thus, in partial or null responders, many clinicians will not be able to characterize the previous exact log10 decline in HCV RNA at various time points in their patients. Therefore, it may be difficult to gain a true definition of null response (Table 2). To characterize a patient as a true null responder, adequate viral data, including kinetics, must be documented and compliance and dose reduction schedules examined. A degree of judgment and subjectivity will be necessary in some patients for characterizing previous response and deciding the likelihood of response."

All quotes from "A Practical Guide for the Use of Boceprevir and Telaprevir for the Treatment of Hepatitis C"
By: Nezam H. Afdhal, MD, FRCPI, Geoffrey M. Dusheiko, MD, FCP(SA), FRCP, Xavier Forns, MD, Donald M. Jensen, MD, Fred Poordad, MD
September 2011

Good luck with your treatment!
Hector

[willbb]

I agree with cando.You  have the eRVR in your pocket (UND. at wk4 and 12)  and you are already at week 14 you say with little side effects. It is all to gain at this point and nothing to lose.IMO

Good luck ..
Will

[lynda607]

Assuming you were taking ribavirin throughout and given the fact that you were on the old type interferon initially, then switched to pegylated interferon and still had a viral load at 24 and 28 wks it would be considered a null responder if only pegylated interferon had been used.  Then you stopped for 3 weeks, went back on tx but you don't say for how long and if you had a PCR that showed UND anytime after you started up again until you stopped for good.  

Lot's of factors in there and I don't think anyone here could say with any certainty what your odds would be this time with 24 wks.  You had an eRVR which gives you good odds of SVR, much higher than 30 percent in my opinion.  Because of the unusual circumstances and the fact that you responded so slowly the first go round I think 48 weeks is wise choice with good odds of SVR.

[can-do-man]

Null Responder: A null responder is someone who achieves little or no decrease in hepatitis C viral load during HCV treatment.

http://www.thebody.com/content/art46371.html

So yes you should be treated as such, that said you are a eRVR which is great, hang in there and do the 48, i wouldn't quit with having that eRVR.

Best to you