Telaprevir SVR Rates Unaffected by Ribavirin Dose Reduction

[flcyclist]

For those struggling with anemia, following is some recent information regarding Riba dose reduction with Telaprevir.  Sorry if it was already posted.  

The data shows that similar sustained virologic response (SVR) rates were achieved regardless of ribavirin dose reduction, including dose reduction to ≤ 600mg/day in a telaprevir-based treatment regimen for both treatment naïve and previously treated genotype-1 chronic HCV patients.[1]

http://www.prnewswire.com/news-releases/incivo-telaprevir-svr-rates-unaffected-by-ribavirin-dose-reduction-in-treatment-naive-and-previously-treated-patients-with-genotype-1-chronic-hcv-147925655.html

[hrsepwrguy]

Yes I was just approved to resume taking 1000 mg riba, we do reach the finish line together, I have 2 days on you that is it. I really think last wk was a lab error, I have been stable at 11.9 and all of a sudden showed a 3 gm drop to 8.9 then 6 days later back at 11.9.

[frijole]

I am stunned.  Happy but stunned at your HGB.  Does this mean that you have increased the Riba back to normal?  Hang in there -- I will meet you at the finish line.

[Proactive]

Speaking of biotech, PI's etc., interesting quote on Amgen's future revenues(reporting tonight)

"Negatives for the quarter may be seen coming from higher Medicaid rebates and FDA restrictions on Epogen and Aranesp."

http://finance.yahoo.com/news/earnings-preview-amgen-investors-counting-170016305.html

[hrsepwrguy]

"head still looks a little off somehow"

Thats amazing that you can tell by just looking, the last person (doc) that told me that, asked me a bunch of questions and made me look at ink pictures before telling me. LOL

Have a great day Will
Keith

[1swimmer]

Thanx for the post re: DR vs rescue drugs fo anemia. I have bookmarked the info in case I need to discuss this w/ my doc. Maybe I'll get lucky, and have a steady hgb.
Cheers,
C

[willbb]

No wonder you still felt good..altho your  head still looks a little off somehow.
Good news Keith..keep on keep-in on..
Will

[hrsepwrguy]

Well I can chalk the 8.9 hgb up to a lab error, this morning my HGB is 11.9 and HCT is 35, the same as it has been since wk 20

Thanks for all the input

Keith

[Willy50]

look at this study w/ boceprevir.  

http://www.natap.org/2012/EASL/EASL_42.htm

A RANDOMIZED TRIAL COMPARING RIBAVIRIN DOSE REDUCTION VERSUS ERYTHROPOIETIN FOR ANEMIA MANAGEMENT IN PREVIOUSLY UNTREATED PATIENTS WITH CHRONIC HEPATITIS C RECEIVING BOCEPREVIR PLUS PEGINTERFERON/RIBAVIRIN

very interesting,
willy

[willbb]

that the timing matters;
----------------------------
Yes ..it would seem so according to all the data released that once one is well into tx. with  a P.I  ,especially if UND. it is the preferred and most successful option (as hersp is  at 35 weeks)
Will

[Willy50]

The first RBV dose reduction trial in effect took place in Prove 2 in the no- riba arm.  They had a 30% SVR rate.

One has to be careful in quantifying what one means when one says dose reduction; how early, how deep of a dose reduction, on what staging of damage, on what type of past responder, whether one is a 1a or 1b, or CC or TT, or viral kinetics of personal response.  
It all will affect this. (or so i think)

I did a quick read, but all I saw was the general admonition that it wouldn't matter, but I would agree more with Cando or Trish that the timing matters; if it didn't why were the no-riba arms failures in the Telaprevir trial.

It is clear that the timing and the depth of reduction does matter.  I haven't studied the latest so I'm not sure how they worded the "Telaprevir SVR Rates Unaffected by Ribavirin Dose Reduction" document, but I wonder if it is a bad title that needs some conditions placed into the sub-heading.

Keep in mind that failure with a PI is to be avoided.  For me, the interesting issue is that a simple dose reduction may work as well as being placed on rescue drugs/ transfusion.

willy

[Trish77]

You may have more say in this decision than you think.  Trials have certain parameters to follow, yes.  But the trial doc has a certain leeway within which he/she can operate.  Rescue drugs like procrit and neupogen were allowed on my trial as well as mandated dosage reductions below a certain point, i.e. hgb dropped below 10.0, automatic ribavirin reduction.  The use of rescue drugs was left to the doctor's discretion.  I was able to successfully lobby my doc to start procrit when my hgb tanked to avoid any more ribavirin reductions after the first one at 13 weeks. If I hadn't asked, I might not have gotten it. My trial nurse didn't think it necessary and I asked to speak to the doc.  However, when my white count dropped at Week 25, it took me 7 weeks of constant pleading to get him to agree to give me the neupogen.  For whatever reason, he wasn't a big neupogen fan and he reduced my interferon instead.  Finally, when that dosage reduction clearly wasn't working, he agreed to the neupogen.  

So...I guess what I'm saying with my lengthy example is that your doc may have some say of his own to bear here.  If it's up to him when he brings in the procrit, you can voice your own preference for using procrit sooner than later as a means of avoiding dosage reduction and that procrit as a means to avoid dosage reduction is your preference.

I find 400mg drastic also.  Is this the trial's dosage mandate or your doctor's decision?  It's like the trial's but I'd ask.

At 35 weeks, a dosage reduction is not as critical as earlier in treatment but it's good to avoid dosage reductions where they can be avoided.

Good luck with all this.

Trish

[Trish77]

Thanks bean, I'm glad to see you're hanging in there and holding that UND.

I think the report is good hope for those who can't do that 100% also - which is why flcyclist is posting it, I think - but is just a little too imprecise, as these reports often are when they lump all results together and come up with a median and report that, but not who the lower end of that median applies to. Always good to dig a little deeper into the details.  

Hope the rest of your treatment goes well and fervently hoping for that SVR for you.

Trish

[copyman]

Agree with the study. I lived it first hand.
I had my riba dose reduced because of anemia during a Telap study back in 2009. Around the 13th week Riba was reduced from 1200mg to 600mg for about a month. Still SVR'd.

[willbb]

cando .agreed  there doesn't seem to be enough data yet on chirrotic's(with P.I therapy),however given the last sentence below it would seem reduction possibly keeps some chirrotic's in the game
Best..
Will

Summary of Key Conclusions
In real-world setting, poor safety profiles for telaprevir- and boceprevir-based regimens in patients with genotype 1 HCV and compensated cirrhosis who had relapse or partial response to previous peginterferon (pegIFN)/ribavirin (RBV) therapy
Rates of serious adverse events markedly higher (38% to 49%) than in phase III trial results (9% to 14%)[2-6]
High rates of discontinuation because of adverse events (7% to 15%)
Grade 3/4 anemia common with both regimens and responded poorly to erythropoietin

http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/Barcelona%202012/Tracks/Highlights%20From%20Barcelona/Capsules/8.aspx

[willbb]

Keith ..As per dosing protocols (both within your trial and also if you were treating clinically)   they are doing dosing correctly . As I mentioned..35 weeks in and with approx. 30 of that UND you should be just fine ..
Hang tough ..
Will.

[hrsepwrguy]

Right at the moment I am on a wait and see basis, I go for labs tomorrow (5 days reduced) and if I have shown a decrease, I will stayed reduced and procrit will be ordered, if I have stablized or show an increase I will be managed by dose reduction on an as needed basis, I really have no say in the decisions, but it was my decision to join the trial and I have to follow thier protocol, the kicker is that if I fall below 8 I will be removed from the trial which I would rather continue than to dose myself and end up being removed.

[frijole]

Good to see you.  You hit it on the head -- we want the edge and every nuance is important.  I also think 100% compliance is important -- none of this 80/80 cr@p.  100%.  

[Trish77]

"Yes this is true, but only once one is Und. Trials showing a lower dose of riba starting out did not work out to well."

As well as lower dose starting out, data showed that reductions in the first 12 weeks on PI's showed low-er rates of SVR than if riba reductions came later on.  For people looking to grab every percentage of advantage towards a cure, the nuances to this are important.  If it were me on treatment again with one of these two PI's, I'd be looking to maintain dosage for the first while as much as possible, without risking health.

[can-do-man]

"and then your remarkable 48 week  trial with Boceprevir under Kwo.  I love his programs on CCO and if he doesn't think riba dose reductions are the way to go, well, I am with him -- and you.

This was his feelings while i was doing the trial and maybe he has changed his mind. I hope to see him after he gets back from the conference. But i would be very surprised if he thinks us cirrhotics should be treated like non cirrhotics and treatment navies... Hang in the bean, it soon will be over.........

[frijole]

horseprwguy
I am on week 35 with VIC and my HGB has dropped again to 9.6.  I have been doing procrit every 6 days.  It is supposed to be 5 but I don't seem to be able to add my days right.    Anyway, interesting this late in the game that yours had tanked so badly.  The riba reduction is a good quick fix, I have found, but are you getting procrit ordered? Oh - re read you are in a trial but I too think down to 400 is pretty radical.

to can-do man
I'm with you, Zach.  In fact I have been with you through your 84 weeks (or was it 96) and then your remarkable 48 week  trial with Boceprevir under Kwo.  I love his programs on CCO and if he doesn't think riba dose reductions are the way to go, well, I am with him -- and you.  Most of the data is for treatment naive and it seems to be holding up.  But there are those treatment naives who will be like me (and others)---at least 36 weeks UND with a test sensitive to 2.  By all standards, I should have cleared - but I did not.  So we need every advantage and that means no dose reductions.

I dose reduced out of desperation.  Insurance issues and absolutely having to get my hgb up to a level I could live with (10).  But as soon as I could I went back to my 1200mg day.  Riba reductions are a quick fix but in the long term, I think epo helps much more without changing treatment protocols.

bean

[flcyclist]

Yes, very good points about cirrhotics, which this article does not address.  I'd also be reluctant to dose reduce Riba if cirrhotic.  I haven't seen similar studies this group.

[can-do-man]

"However, few cirrhotic patients were included in these trials."

Would like to add i was in the Phase III trial for boceprevir and one of the cirrhotics. Kwo was the Principal Investigator and was very much against dose reducing us at any time, and i not sure theres been much data on SVR cirrhotics at this time for minds to have changed... Maybe though.

[can-do-man]

Kathy makes a good point on cirrhotics and how they should be treated as not many were in these trials. As we know one size does not fit all when treating HCV.

Phase III trials have shown that Telaprevir (TVR) is associated with frequent dermatological disorders and anemia, whereas Boceprevir (BOC) is associated with frequent anemia. However, few cirrhotic patients were included in these trials.

http://hepatitiscresearchandnewsupdates.blogspot.com/2012/04/easl-2012-safety-of-telaprevir-or.html

[frijole]

Well I see Incevik is getting on the band wagon too - like Victrelis.  

However, there is still not enough information specifically on relapsers and cirrhotics.  I hope the information posted in new studies is correct, but until they sort out the "hard to treat" I find the information significant only to treatment naive who (as can do said) have already achieved a UND.