New guidelines say reduce Riba first for anemia

[sandysf]

I was just reading the post from HectorSF from the AASLD and I have also read similar information at the Clinical Options site.  The new guidelines recommend Riba dose reduction with the new PI's when anemia occurs as it has not been shown to reduce SVR chance.   I know this topic of reduced riba has been debated many times on this forum.  But as it pertains to triple therapy.. I get the feeling that researchers are comfortable based on the data that reducing riba is as effective without impacting SVR as using procrit.  

My question though is nowhere can I find the guidelines on reducing riba in triple tx.   Reduce by 200 mg as a first step,  but for how long?   If you reduce riba after UND is it safe to stay on reduced riba for 11, 12 weeks?   The research doesn't seem to be clear on exactly what level of reduced riba is safe without impacting SVR chance.

[Diamando6]

No Sueze, I was not on triple therapy, only on SOC , which is Pegasys and Ribavirin, for 48 weeks. I was UND , at week 12, but again detectable, at the week 48., I was all the time at dose of 800 mg of Ribavirin. I think it was not enough, for achieving SVR.

[willbb]

It seems at when the time of UND. is more important than the actual week...according to Shiffman..
.

[copyman]

Just to clarify,

My point about the reduction was that only reducing by 400mg can have an impact on a persons HGB increasing. Much better then rescue drugs in my opinion. Reducing riba should at least be tried before procrit.

I would be leery lowering riba before 12 weeks. I would consider rescue drugs if is was before at least 8 weeks. Usually HGB drops after 8 weeks which is plenty of time for riba to have built up in a persons system.

And I only say the riba reduction is better if on triple therapy. If on SOC only then NO reduction of peg or riba.

[sandysf]

Thanks for all the comments.. the real answer I suppose with the new drugs is that we just don't know yet.  There is just not enough data and we are all guniea pigs of sorts with this new PI's right now.  

We shall see... but I am with copyman, I would rather have my riba reduced than put yet another drug in the mix.  

[frijole]

No matter what the studies say, I am glad I don't have to fight the battle.  Procrit should be on my doorstep when I get home tonight and boy, am I looking forward to that burn!

Even if you add all those studies together, how many people are we talking about? Low thousands, maybe?  Seems I read that 17,000 people have started INC since May.  Anybody heard how many Victrelis patients there are?  What I would like to see is surveys done by the two drug companies filled out by the doctors on HGB levels, treatment (riba reduction, procrit, transfusion, other) and, of course, outcome.

frijole

[desrt]

It's long been known that riba does its 'heavy lifting' (even for SOC) during the early part of tx. The 'scarfle-riba-till-your-ears-bleed' torch people never had reason on their side, other than it was a cheap, easy way to tweak your tx.

desrt
who (at 100 kg) dose reduced from 1200 to 800 and wasn't anywhere close to anemic)

[Trish77]

Copyman: That's not much of a dosage reduction to be basing an opinion on that dosage reduction of ribavirin isn't harmful because you did and you got SVR.  One week dosage reduction of riba on SOC after Week 12 is considered acceptable and you had two and then none again at all.  That's a drop in the bucket for dosage reduction comparatively.

As for the rest of it, the devil is in the details, seems to me, as Spectda points out.  How many were dose reduced, by how much and what do other studies say?  I've seen a solid study posted by someone else that clearly indicated the impact of dosage reduction of SOC during triple therapy.  Slight drop in SVR rates across the board.  I personally don't think there's enough data out on this yet to make me comfortable with reducing Riba as a first choice when HGB drops and I'd like to see more data coming out of "Phase IV" first.

Trish

[copyman]

I reduced the riba at week 13.  From 1200 to 800mg for around 2 weeks. HGB shot right back up then back on full dose until I stopped TX around week 28.

[nowhine]

Wow...great information guys and gals. Thanks for doing the research.

Knowing all this information and the potential for no interf/riba in the near future would you start treatment now or wait?

[nygirl7]

Maybe the devil you know is better than the one you don't know. Only time will tell who really are the nasties. ."

Nasty, nasty boys, dont mean a thing....
Oh you nasty boys.

;)

[suezeeque]

Was your last treatment with triple therapy?

I'm in a PI study and was told going into it that if necessary, my riba dosage would be reduced by 200 mg a day (incremenets, increasing if necessary) FIRST.  And the dosage would remain lowered as long as necessary.

[Diamando6]

I would rather go for rescue drugs!

[Diamando6]

I think, that one of the reasons, I fell to achieve SVR in my last treatment, is that I had to reduce Riba dose, since my low platelets and wbc! After I read in some articles, that Riba dosage is very important!

[Diamando6]

I heard, that Riba level is much related to SVR outcome.

[beeblessed]

Oops, meant to thank Copyman and Will too.

[beeblessed]

Sandy -- Wow.  My mind is reeling.  Thanks very much for posting this question, as the info here helps me too.  Trying to see what is best, without 'doctoring myself', is a bit of a balancing act today.

Spectda, Hector, Bill, Can-do-man......thank you for doing your homework and shedding some insight on this debate.  I really do think it is a different ball game with the P.I.'s, not quite as cookiecutter as they (the great and powerful Oz of Merck and Vertex) anticipated.   Maybe that is why we are seeing so many different moves from doctors, from patient to patient.  Either way, I am taking everything your have said here very seriously.  Thank you.

[spectda]

They didn't use procrit in the inci trials. They used it pretty freely in the Boceprevir trials.
-Dave

[sandysf]

Thanks Hector!  I was actually looking for Boceprevir data since I am on Vic.. but this is great information and likely applies.  I am digging around on natap site now to see if I can find the same data for BOC.

[spectda]

Great information Hector. I am confused by the statement below. I assume all of the people were not reduced to 600mg per day although perhaps they were. It would be good to know what HGB levels were vs what level of ribavirin reduction was used.

"The dosage of riba was reduced to 600 mg/per day according to “package insert directions.”

-Dave

[HectorSF]

Sandy,

Here is the data the source documents referred to in the new AASLD Guidelines for telaprevir that you asked about in your questions. (Others can read the data on boceprevir).
-----------------------------------------------------------------------------------------
24. Sulkowski MS, Reddy R, Afdhal NH, Di Bisceglie AM, Zeuzem S,
Poordad F, et al. Anemia had no effect on efficacy outcomes in treatment naive patients who received telaprevir-based regimen in the
ADVANCE and ILLUMINATE phase 3 studies. J Hepatol 2011;
54(suppl 1):S195.

http://www.natap.org/2011/EASL/EASL_41.htm

Results:

41% (361/885) of patients in the T12PR developed anemia (hemoglobin < 10 g/dL) during treatment. Seventy four percent (267/361) of T12PR patients with anemia achieved SVR.

Seventy three percent (384/524) of T12PR without anemia achieved SVR.

Seventy-two percent (260/361) of T12PR patients with anemia had ribavirin dose reduction due to adverse events compared to 11% (60/524) of T12PR without anemia, respectively.

SVR was achieved by 76% (243/320) of patients with ribavirin dose reduction in the T12PR compared with 72% (408/565) of patients without ribavirin dose reduction in the T12PR.

Conclusions:
In patients treated with telaprevir-based therapy, anemia as well as ribavirin dose reduction had no apparent effect on SVR rates. These data suggest that management of treatment-related anemia with ribavirin dose reduction appeared not to impact SVR with telaprevir-based therapy.

"Reduce by 200 mg as a first step, but for how long? "  
"If you reduce riba after UND is it safe to stay on reduced riba for 11, 12 weeks? "

Hemoglobin <10 g/dl is considered anemia.
The dosage of riba was reduced to 600 mg/per day according to “package insert directions”.
Time of first Ribavirin dose modification appeared not to affect SRV rates.

7 days was considered “dose interruption”

76% (24 weeks) and 73% (48 weeks) with “dose interruptions” achieved SVR.


Cheers!
Hector

[mikesimon]

I suppose it’s only a matter of time now before the nasties are morphed out of the equation.

Maybe the devil you know is better than the one you don't know. Only time will tell who really are the nasties.

[willbb]

suppose it’s only a matter of time now before the nasties are morphed out of the equation.
----------------------------------------------------------------------------------
Kinda my thoughts Bill...but will take some time huh. .... but that Inci ,is quite a nasty...from what folks have been reporting.... :)
Will

[Bill1954]

Wow; all four study arms and none of them involve either IFN or riba. Treatment is certainly changing, Dave. I suppose it’s only a matter of time now before the nasties are morphed out of the equation. There’s likely to be a substantial pay day for the companies involved, hmm?

Thanks,

--Bill

[spectda]

I thought this was interesting although it's about a year and a half old:

http://www.natap.org/2010/HCV/050610_01.htm
"from Jules: in 2011 the first 2 protease inhibitors are expected to become available as they are in phase 3 studies now and will be used in combination with peg/rbv. Over the following several years numerous additional oral HCV drugs in a number of different classes are expected to become available as now there are about 25 oral drugs in development. It remains to be seen if peg/rbv can be eliminated from therapy. Drug classes include protease inhibitors, several types polymerase inhibitors that may be able to be combined in 1 regimen, NS5A inhibitors, and there are 2 new interferons in early clinical development, lambda interferon and locteron, that appear to have less side effects than the peginterferon used now. I expect eventually therapy will be reduced to perhaps 12 weeks for some patients but even in 2011 duration of therapy with 1 oral +peg/rbv will be 24 weeks. Combination therapy in the future will consist of several oral drugs - 2, 3 or even 4 - with or without peg/rbv. Oral drugs are expected to be equally effective in all ethnicities so there should not be major barriers to curing African-Americans and Latinos if testing/screening, linkages to care and patient services are adequately providing and if we can prevent too much drug resistance."