Avatar universal

Lowering Ribavirin Dose

Have any of you seen the new study out of Johns Hopkins regarding comparing the two Pegs? Apparently they also looked at lowering the dose of ribavirin (and interferon) when anemia occurs and found that actually improved the success rate of SVR when compared to people who toughed it out and stayed with the same dose.

I was floored when I read this and wish I knew enough to know just how good this study really is. I have a lot of respect for Dr. Sulkowski. Maybe we will get to hear more about this at AASLD.
19 Responses
87972 tn?1322661239
Wow, do you have a link to this? It surely is counterintuitive, isn't it? I wonder how the study was structured... was it sound? Am I asking too many questions :o)? Thanks; I'll keep an eye out for it,

Avatar universal
That is sure not how it has worked for my husband.  He is now a 3 time non -responder.  This time he is been on interferon since June 2008.  The last 20 weeks he was switched to Infergen because he could never get to nondetectible.  Viral load just stays in the small numbers.  The lowest it got was 80 but last time it went up to 300.  I don't expect they will leave him on it any longer.  We have just tried everything. He has also been on Alinia since May 2009. We predosed Riba and he took a good dose most of this time (1200-1400) but a couple of months ago his hgb dropped to 7.2 and he had to have a transfusion.  They stopped Riba for 2 days and have changed his dose to 800mg. and low and behold his viral load went up instead of down.  Similar pattern in the past.  Ribavirin seems to be pivotol for Joe.  He has taken loads of procrit but eventually it wasn't working well enough to keep him out of trouble.  
I find this study very confusing.  Maybe it is just like this in people that were probably never going to SVR anyway.
Thanks for bringing up so many interesting thing to the board.
Avatar universal
Here is the link:

87972 tn?1322661239
Banarep; thanks for the link.


“In a piece of reassuring news, the study appeared to allay fears about switching to less aggressive drug treatments in response to severe side effects with anemia, showing it can be safe and effective to reduce the does of the antiviral drug ribavirin to doses below those initially prescribed.

Moving forward, researchers say the higher rates of viral eradication in infected people in the early stages of liver disease warrants more widespread screening in people at greater risk of being infected, such as those with liver inflammation, anyone who received a blood transfusion before donor testing for hepatitis C began in 1992, and injection-drug users.

Researchers also found that in the third of study participants whose ribavirin dosage was reduced as a result of anemia, cure rates actually improved to as high as 52 percent, whereas in those whose ribavirin dose stayed the same, cure rates were lower, at 37 percent.

“Contrary to the prevailing belief that ribavirin dose reduction would lead to fewer people recovering from their infection, it actually increased the sustained viral response rate when reduction was used to manage treatment-related anemia,” says Sulkowski, who attributes the onset of anemia as a sign that the body had sufficient ribavirin to fight off the infection.

“Our study shows that in infected people having difficulty tolerating standard dose therapy with peginterferon alfa, we can safely reduce their medication levels,” he says.”

This study apparently involved both Schiff and Shiffman as well; all good investigators; it will be interesting to see more.

179856 tn?1333547362
Maybe they are insuinating less drop outs from the anemia? It sure sounds completely incorrect and against everything we've ever seen previously and I still wouldn't do it if it were me.
Avatar universal
Sorry, I was at the supermarket. Thanks for posting the link. I will try and speak to Dr. Sulkowski in November.
264121 tn?1313029456
ok - upon reading the actual study, it seems to me that what they are saying is that when people are effected with anemia to the point that their ribavirin has to be reduced in order to complete the treatment, this is a good indication that the ribavirin is working as it is supposed to and those patients who had that level of anemia attained SVR more often DESPITE the reduction by up to 50% of the riba.

"Despite the reduction of ribavirin dose by as much as 50% in patients receiving peginterferon alfa-2a, patients with anemia had a higher rate of sustained virologic response than did those without anemia, suggesting that the magnitude of anemia may be a pharmacodynamic marker of drug exposure. The data indicate that the initial ribavirin dose should be at least 13 mg per kilogram per day and that the conservative management of anemia, involving a ribavirin-dose reduction in either one or two steps, appears to maintain safety and not to compromise efficacy."

Actually, we've heard that before on this forum, I'm not certain in conjunction with which study, but I do remember having it mentioned when I was having anemia during tx.
264121 tn?1313029456
that would be... affected / not effected (sigh)
683664 tn?1330966324
"The disease, transmitted by contact with blood and other body fluids of an infected person, through sexual activities, injection drug use or sharing of personal care items, kills more than 10,000 Americans annually."

Well, here's one of the reasons we get so many folks asking about sexual transmission.  Ruh roh...  It says so right here.

Meanwhile, I find this very interesting in light of my own recent tx experience with no rescue drugs for anemia.  Of 24 wks of tx, Ribavirin was reduced for 7 weeks total (first 3 weeks, later 4 weeks) due to anemia.  My hgb went below 10 at week 3, which seems early to me, from reading other posts.  

Here's my curiosity.  We know that sides (their number and severity) generally do not predict response to tx or SVR, and that, conversely, anemia signals a therapeutic response to Ribavirin.  Since the PI's also cause anemia, I wonder if we're seeing a link between degree of anemia and SVR.  Is that what they're saying?  What do you folks think?  Just please don't eat me for dinner : )

264121 tn?1313029456
Right.  They are saying that degree of anemia correlates with higher SVR rates, even though  at times they had to cut the ribavirin by up to 50% in those individuals.  When I was on tx, the riba ate my rbc's like they were little pacmen.  It happened very quickly.  
Avatar universal
Since plasma level testing of ribavirin is rarely available in th eUS they use anemia as a barometer of the adequacy of dose. If you have enough ribavirin to kill a lot of RBCs then you're probably dosed high enough and if you don't present with anemia then the dose is likely too low. Note that in renal impaired patients the dose is often decreased because lower doses result in higher plasma levels when the kidneys function is impaired. I think looking at anemia as a marker is just a relatively cheap way of measuring the adequacy of dose.
Avatar universal
I believe I saw a study recently where it said it was crucial for SVR to keep the dose of ribavirin not only for the first 12 weeks but during the entire tx period.
691935 tn?1421027090
The study was actually a comparison between the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin.  

In addition to the reductions, I thought it was interesting that women may have higher rates of sustained virologic response with standard-dose than with low-dose peginterferon alfa-2b.

Here's the link to the actual study:  http://content.nejm.org/cgi/content/full/NEJMoa0808010

Avatar universal
Cirrhotics can have a low hemoglobin before even starting Tx so it makes sense that this barometer wouldn't work as well once you were to stage 4.  Your labs just don't have as far to fall before you get in trouble when you start Tx with cirrhosis.
250084 tn?1303307435
It's late, tired and slipping into this thread here but.....

I see no mention above as to geno types. Being a 2b,my reductions were a better route versu stopping tx , etc. while that, thus far in tx/soc, is not such a safe move for geno 1's. Like Alagirl, my hgb went south fast. I achieved SVR with reductions, but I was Geno 2.

Back when more alert ;)

568322 tn?1370165440

This study recommends maintaining as high a ribavirin dose as possible during the full treatment period to prevent relapse.


J Viral Hepat. 2009 Jun 22.

Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin.

Hiramatsu N, Oze T, Yakushijin T, Inoue Y, Igura T, Mochizuki K, Imanaka K, Kaneko A, Oshita M, Hagiwara H, Mita E, Nagase T, Ito T, Inui Y, Hijioka T, Katayama K, Tamura S, Yoshihara H, Imai Y, Kato M, Yoshida Y, Tatsumi T, Ohkawa K, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N.  Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.

The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis (P = 0.002), the timing of HCV RNA negativiation (P < 0.001) and the mean doses of ribavirin (P /=12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 mug/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (>/=12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in complete early virologic response (c-EVR) patients.
Avatar universal
I wonder if this bears on riba trough levels and not the number of pills one takes?

People with higher trough levels might experience more anemia and therefore be fine with less riba since they are getting more *bang for the buck.*

In some respects the results should not be too surprising if they factored in discontinuations (which would affect the success rate) caused by the higher riba dosing.  

I think you would have to be careful interpreting this too quickly and simply.
(ie: lowering the riba= higher success rate)

691935 tn?1421027090
"People with higher trough levels might experience more anemia"  I'm thinking the same thing Willy.

Also, I'm wondering if the reduction brings the person back to a state of health to where he can get a boost to be more able to fight it.
264121 tn?1313029456
I think you would have to be careful interpreting this too quickly and simply.
(ie: lowering the riba= higher success rate)
I think it's pretty apparent if you read the study that this is NOT what they are saying.  In fact, they clearly state that maintaining appropriate riba levels is important in general.  What they ARE saying is that a fairly high percentage of people who register severe enough anemia that their riba has to be reduced are achieving SVR.  They are postulating that the anemia is an indicator - as Mike said - that the riba is therapeutic in those folks.  It apparently continues to be therapeutic in those folks in spite of having their riba reduced by up to 50%.  
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