Need Advice on Tx course

[BostonGirl]

I know many of you have done tx 2, 3 times and have a lot of experience, so I trust your judgements. I really need some help here.

I recently had my 12 week PCR. I was previously 55,967,000 and dropped to 19,000. That is a great drop and I am pleased. ( I am 1A, so 48 weeks required )But now, all my doctor agree that 18 months, possibly longer GGGRRR> of tx will be required.

Now here's the part that is confusing. Early into the tx,like the 3rd week my PCR dropped to 303,000 which means 9 weeks later ( at the 12 week mark )I didn't really drop that much.

I e-mailed Dr. Cecil and asked for his advice. His opinion is that I need double doses of Peg or I should switch to daily infergen.

I am also having progression in my cryo. So, I will be seeing another specialist about possibly adding another drug to tx the cryo during the Peg treatmemts.

My questions to slow responders > would it be beneficial to do double doses of Peg at this point or switch to infergen? My doctors seem to think I should continue the current 180 per week and just extend the tx.

Also Dave, I know you did that additional drug for your cryo and I would like to know at what point into tx did you clear the HCV and cryo? were you also a late responder to the Peg? And do I need to be clear of HCV to start the rutuxin? The Hemo said she has mixed feelings on using this drug, but we will talk about it if I still have cryo at 6 months. meanwhile, I am getting a second opinion on the cryo and doing a lot of praying.

Thanks ahead of time for all your resposes. ((( Sue ))

[bon_vivant]

Hey.... I say the longer the better... & especially in your situation... (because you did not clear completely at 12 weeks)

On my first round, I had over a 4&1/2 log drop at 12 weeks...  but was not completely clear.... (This should have automatically bumped me up to the 72 week mile marker)....

I was Undetectable by 24 weeks (even with the wrong dosage) so I am definately a responder.... I was still clear 2 weeks after my TX ended the first time... but by the 3 month ck up... I had relapsed....

I wish I would have extended THEN.... because, in all probability, I'd already be done with it by now, & not doing this second round...

So YES, YES... extend as much as possible the first time...
Why Risk it.... better to add to an already existing 48 weeks... then to have to start all over from square one again!!!!

Just My Opinion!!!!
:)

[willing]

a very rapid initial drop in viral count which slows until the virus drops below the detectable level is the standard response and doesn't indicate there's anything wrong (virus begets more virus, also as the ifn turbo-charges your immune response, it's much easier for it to first eliminate free virions in blood serum than virus replicating in cells). In making  decisions about how long to go and how much ifn to take it's worth taking the time to evaluate the basis of advice you receive. The most reliable recommendations are those based on the large-scale studies since they yield believable odds for various outcomes. Unfortunately, as in your case, there's never enough data and it comes down to judgment, or informed guesses. I haven't kept up with recent studies since I finished tx but, with  all due respect, I doubt Dr. Cecil has much data to support his advice. If you look at the response rates you'll find that most of the time when combo tx works it starts working early on. Your 3.2 log drop is pretty compelling evidence it's working, but the fact that you're not undetectable at 12 lowers your response odds significantly.  To find out whether going to 72weeks will really help those odds it's probably worth digging through the current studies. I went through the same issue around my 12th week and decided not to extend past 48 since what little data there was  showed little benefit. However I'm sure more studies have been published in the past 1.5 years, and your drop is typical of the  "slow responder" most likely to benefit from extented tx (besides, the cryo may provide its own reasons for continuing)..best wishes

[BostonGirl]

Thank you both for your comments. I appreciate them very much. I guess there are no easy answers when it comes to this dreaded virus.

I do know that the first phase the drop in the viral load is usually the most rapid. Then as it tapers off into the second phase, the viral decline is much slower.

I have been reading and all the data points to extended tx for slow responders. ( i knew that going into this ) I am willing to do so, just a bit concerned that Dr. Cecil seems to think extended tx will not benefit me at all.

I assumed Cecil was up on all the latest studies, maybe I am wrong? I really don't know anyone that has treated with him, only that he has treated many thousands of Hep people and has a high success rate. How do most of you feel about Dr. Cecil in general?

Thanks again ((((((( Sue ))))))))

[twotells]

Sue, It's tough to have to make a decision about this, especially since you have had a good early response.  Frankly, my GI's were always guarded about my chances of going to SVR, because of the cryo, even when I was clear at 12wks.  They always seemed to think the cryo was a factor, even though I was treated for it and the Hematologist told me "we took care of that (cryo), and you don't have it anymore."  There are some reports as well as a study showing the usefulness of taking care of the cryo with rituxan when treating for HCV.  I imagine your hematologist would have mixed feelings since the rituxan would be off-label for cryo (it's a lymphoma drug and using it for cryo is very new).  My understanding is that it is safer for people like us, without cancer, than it is for people with alot of cancer to clear.  I really believe that the Rituxan helped me achieve SVR by removing the cryo, which somehow interferes with SVR.  The rheumatologist that I just saw, commented that he would have recognized the cryo, but that he wouldn't have used Rituxan and he considered me fortunate to get the care of my hematologist because he did use the Rituxan.  I wish you the best, and hope the second opinion is helpful,  Dave

[layla]

It was the same with me though I don't have the exact numbers I had with me now. Regardeless I was not clear at 3 months even with a good inital drop. I immediatley knew I wanted extended tx and had already addressed this senario with my doc. We both felt this was the way to go. The only difference was I thought I should do 36 weeks form clearing and he said he really thought I should do 48 weeks from clearing soooo that is what I did. At 10 months post tx I was still SVR.  It can be done..... It's very very tough to do full dose tx that long but I would recommend it in your case too. I did work the whole time for whatever that is worht. What are your other options? Infergen would be next. No thanks is my though unless I've tried everything else first. I would try this first at 18 months at full dose. I really do feel for you and if you want to chat just email me anytime. ***@****. LL

[twotells]

I was symptomatic, with a cryocrit of >7%, and I did do the rituxan at the same time with little, if any, added side-effects from the Rituxan.  The biggest risk with Rituxan involves a type of shock that can occur with people that have large amounts of cancer.  People without cancer don't have that risk.  In most people, the cryoglobulinemia resolves with Peg-interferon and Riba (so I'm told).  That would make my experience rare, since my cryo became dramatically worse following the start of combo tx for HCV.  The Rituxan is expensive ($20,000 for the series of 4 infusions) and not labeled for cryo, so my insurance (Aetna at that time) balked initially, but then was persuaded by my Hematologist/Oncologist to pay through the prescription plan.  

My biggest problem then and now is the peripheral nerve damage sustained during the 5 months it took me to have the cryo diagnosed and Rituxan treatment approved and started.    My biggest improvement with the cryo related neuropathy came in the month following the Rituxan treatment.

I wish you success in your treatment,  Dave

[Tallblonde]

Did you know that more than 75% of people with HCV test positive for cryoglobulins?  I'm one of them, but I don't have cryoglobulenmia, according to both of my GI's.  I'm wondering if you're just someone, like me, who has simply tested positive for it.  

If you still have the copy of your cryocrit lab results, could you please tell me exactly what it says?

Here's what mine says from my 12/04 test:


Cryo Quantitative Bl              63          (>50 = High)


By the way, when I was first tested for cryo 18 months ago, the result was 83.  But like everything else (viral load and enzymes), it has decreased.

Any thoughts?

Susan

[twotells]

I never actually saw any numbers on reduced odds for people with cryo reaching SVR, but the GI's all seemed convinced of it.  This is the link for a study on the safety and efficacy on Rituximab for Cryo:
http://www.bloodjournal.org/cgi/content/full/101/10/3827
Take care,  Dave

[cuteus]

it is nice to see you are still checking up on MH, the wealth of information you share is invaluable and irreplaceble. I wish you had time for more visits.

[TnHepGuy_]

Here's a new study that may be somewhat applicable in your case: <a href="http://www.hivandhepatitis.com/2005icr/ddw2005/docs/hcv_052305_b.html">Correlations Between Rapid Virologic Response (RVR), Early Virologic Response (EVR) AND Sustained Virologic Response (SVR) in HCV Genotype 1 Patients Treated with Pegylated Interferon Alfa-2a (Pegasys) and Ribavirin"</a>. (I say "somewhat applicable" since in this study they used tx-naive patients and in your case you have already done tx on multiple occasions. Even so, I believe that the data here can be useful for your decision making.)


You experienced a >2 log decrease by week 12. The chart in the above study shows that the 23% of patients who received a >2 log decrease by week 12 (but did not become undetectable) had an overall SVR rate of 26% for a 48 week tx time-frame.

Given that you've tried tx before, the fact that you have cryo  and the low SVR odds (26%) shown here for 48 weeks on tx-naives, I'd think that a full course of 72 weeks should be considered in your case. You'd (of course) want to get another PCR done no later than week 24, to be sure that your viral load has continued decreasing (hopefully to undetectable). And make sure that your doc will be proactive in keeping your dosages at full amounts via early intervention with Procrit and/or Neupogen, should either of those be needed based upon your bloodwork.


As far as doubling the dosage of the interferon, there have been conflicting reports in the past about it's effecacy, but here is a new study showing positive results: <a href="http://www.hivandhepatitis.com/2005icr/ddw2005/docs/hcv_051805c.html">Double-dose Peginterferon Alfa-2b Plus Weight-based Ribavirin for Retreatment of African-American Non-Responders with Hepatitis C</a>.

Here is another new study you may find of interest: <a href="http://www.hivandhepatitis.com/2005icr/ddw2005/docs/hcv_051605a.html">Sustained Virologic Response (SVR) with Peginterferon Alfa- 2b (PegIntron) Plus Ribavirin Weight-based Dosing in Previous Interferon/ribavirin HCV Treatment Failures: Week 12 Virology as a Predictor of SVR in the EPIC3 Trials</a>

Also, here's a recent study looking at: <a href="http://www.natap.org/2005/HCV/050305_02.htm">Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study</a>



May God's blessings and mercy be upon you.


TnHepGuy

[twotells]

Here's a link for a controlled study on Rituxin (Rituximab) for people with HCV and Cryoglobulinemia:
http://www.bloodjournal.org/cgi/content/full/101/10/3818
God Bless,   Dave

[twotells]

In the second study (Domenico Sansonno et al) they mentioned increased viremia (increased viral load) with the Rituxan alone and  suggested the potential synergistic value of treating with Rituxan and anti-viral therapy (at the same time).  That is essentially what my experience may demonstrate, ie. that the Rituxan and Peg-interferon/Ribavirin may work best together.

Have a blessed day,  Dave

[rearfang]

I am so glad to hear from you! I guess you're probably out enjoying life and catching those van Gogh exhibits? Anyway, don't be a stranger! Your input has always been most valuable.
Lauren

[willing]

TN - as always, great references - you are a master at locating relevant information. Hope post-tx life is treating you well.

Sue: from the second line of the table TN posted, it looks like your initial drop was rapid enough that you're currently looking at about a 60% chance of SVR (log(55967000)=7.7 and log(303000)=5.4 so you had a 2.3 drop by 3 weeks). This is getting pretty close to the 70% you could expect if you had come up undetectable at 12. You should probably keep digging to see how likely you are to recoup that 10% by adding 6 months. My own bias is that tx is the best option we've got but trying to force a good result by persistence is sort of like forcing a frozen screw with a screwdriver that's the wrong size - damage is more likely than success.

[TnHepGuy_]

Thank you for the kind words and for asking about me.

I hope all is doing well in your folks necks-of-the-woods and that 'willing's '1-person post-tx study is coming along nicely.

I've jumped back into life head first and it has left little time for things Hep C-related. I still try and check on the latest releases of info and studies and continue peek in here from time-to-time. As far as my physical recovery goes, I'm 4 1/2 months post-tx now and only recently have my white counts returned to normal range. And I'm one of the 15-20% who take a long time for the red counts to rebound (5-10% never do), so at this point I'm still slightly anemic - though the counts are still moving upward, just at a snail's-neck pace. Other than that particular problem, some degraded eyesight and very occasional and intermittent bone pain in my hip, there haven't been too many lingering physical manifestations from the tx.


As far as the Reddy study, I'm cautious to draw a true direct parallel to BostonGirl's case since she has tx'ed prior (though I don't know if she relapsed or was a non-responder) and the patients used here were tx-naive. But in the attempt to make this study useful in her particular case, I chose to use the data from the 'Week 12' area of the chart because, even though she reached the >2 log drop by Week 4, she currently falls into the >2 category for Week 12 by virture of her PCR not showing clear at that later point in time. With that being the case, she then would have a 60% chance of her Week 24 PCR being clear and an overall 26% chance for SVR (based upon a 48 week tx).

Add onto all of this that she's tx'ed unsuccesfully twice before and has cryo - and that 26% SVR figure may be optomistic, at best (unless her prior tx'ing was sub-optimal due to initial under-dosing, dose reductions, etc - in which case she could effectively be considered 'tx-naive' to a full-dose tx regime). So, being that I'm from the school of "tx once, tx best-you-can", I think 72 weeks of closely monitored tx would be her best shot at waving goodbye to this invader once-and-for all.


TnHepGuy

[twotells]

It appears that this K. Reddy may be the same guy who did my biopsy and started my treatment- and later recommended the 48wk titrated extension.  Does he work at U of Penn?  It's not important, just interesting to me.  Later,  Dave

[willing]

twotells - I believe it is : the presenter of that session is on the faculty at U.Penn

tn: the irritating part, for me at least, is that improving patients' perspective of where they are on the treatment landscape is a problem with a relatively simple solution - better data management - yet it gets very little attention. Designing more effective drugs or understanding the mechanisms of response await significant advances in basic science, but giving patients a realistic sense of their likely outcome could be addressed today  with as simple a solution as requiring Roche and Schering to maintain publicly  accessible databases where users could, voluntarily and anonymously, choose to deposit all test results throughout treatment. Then instead of estimating your outcome on the basis of scarce data, incompletely reported, you'd have the benefit of the experience of the thousands of patients with a profile similar to yours who had preceded you (if you can't be an organ donor, be a data donor..)

[BostonGirl]

I would like to thank all of you who responded to this question. It is a bit complicated and I am still sorting through all the data. There's a lot of great information at this site and I really do appreciate all who post the studies, articles, and give their personal opinions. I thank you all from the bottom of my heart.

As far as treating prior to this go round > No, I have never treated with any interferons. This is my first shot at it. I have been on full dosages the entire 14 weeks, never reduced. I was put on procrit instead. I refused reductions, so they gave me procrit right away.

When first diagnosed with Hep C in 2002, I was doing alternative tx's, for a couple of years ( with great success ) But by the end of 2004 my viral load skyrocketed, I got really sick and everything else just seemed to go down hill from there. My herbal regimen did not change, I was eating organic, kept a low body weight > doing all the right stuff, but it just wasn't working anymore for me.

I will keep you all posted on what decisions we have made. Right now I am continuing the full dose Peg tx and setting my goal for at least 72 weeks. I only want to do this once.

Thanks again everyone and God Bless you all for this forum.

(((((( Sue )))))))

[willing]

yes, that very small study is chugging along, though I think my Dr.'s might be getting a tad irritaded by my procrastination. Life is good.

you're right about my being overly optimistic about the 60%. However, I also believe the 26% is unduly pessimistic and that the best estimate of Sue's current outlook lies somewhere between those two points. The trouble is the tables don't give a complete breakdown  : how many of those 242 patients who had a >2 drop by week 4 were still detectable at 12 ? and how many of the 133 who were detectable at 12 had benefited from a >2 drop by week 4 ? By picking either 26% or 60% you're throwing away part of the available information. I wrote to Reddy to see whether he would release the actual vl counts( probably not, I've tried with Roche before). The best prediction would use all the available information, including actual VL counts rather than binary cuttoffs, but this requires the actual data...it's unfortunate drug companies are so closed to making it available.

[TnHepGuy_]

I'm glad you wrote to Reddy and I hope you get a complete response.

I, too, was concerned when looking at the percentages, that patients can overlap and 'bounce' in and out of various categories. To come up with 'true' SVR figures, they would need to have a more exacting breakdown that would separate them all the way through the study, as you suggest.

The good news for BostonGirl is that she is tx-naive. The bad news is her extremely high starting VL figure - though the encouraging news there is the very large, continuing VL drop by week #12. As far as the other 'big' factors that go into SVR predictors (liver histology, age, sex, BMI) - only one of these is obvious. Assuming the others are in her favor (no higher than Stage 1 liver damage, age 45 or below, normal BMI), then I would suggest that she monitor her VL every 4 weeks past week #12 to best determine when the point of undetectability is reached, then tack on a minimum of 36 weeks more of tx. If liver histology is an issue, then I would consider going for the full 72 - both for SVR chances and for potential histological improvement via the interferon.


(note on very high VL figures: - I think the Hep C medical/research community is doing a great disservice by lumping anyone above the 2,000,000 mark into a single category of 'high' VL. For example, mine was 2,400,000 going into tx, putting me at the low end of 'high'. Yet someone such as BostonGirl (with a VL of 56,000,000) is catagorized (as far as studies and trials go) the same. This seems rather unreasonable given how well known the inverse relationship is between VL and SVR. I think a more detailed approach of three or more categories would be of benefit to researchers, doctors and patients - giving all a more useful info to work with and therefore a more focused approach to tx).




TnHepGuy

[cuteus]

I was going to bring up that national database issue.  I think it is a must, but I am afraid that if we allow the drug co. to obtain and handle that input, that some numbers might get manipulated...are you working on this project?

[BostonGirl]

Yes, not only am I treatment niave, my BMI is 20, I am 44 and premenapausal, so still having plenty of estrogen, and I am fairly thin. My biopsy in 2002 showed stage 0/1 no fibrosis grade 2 inflammation. I have many factors in my favor.

My high vl and the cryo are definately not in my favor. But, I am going to continue tx and keep believing that this dragon will be gone.

The plan now is to have viral loads every 30 days, so we will know when I clear. Then, we will consult Dr. Ahmed from Stanford Liver center. He's been treating HCV for many years. He also is the Head of the transplant unit. I trust his judgements.

We will also consult my hemo and the rheumy when all the test results for cryo and vascultis come back. So, in about another 2-3 weeks I will know exactly where I stand. Thanks again for all your great links and posts. I do appreciate it.

((((((( Sue )))))))))

[willing]

to the best of my knowledge there is no such project underway. In the unlikely event I actually get the source data from the Reddy et al study I'll post the more detailed breakdown. The drug companies already have access to most of the available data : if you look at the disclosures statements for most of these studies (including the Reddy one) you'll see Roche or Schering as the funding source. The trouble is they don't provide access to what they have. Putting together a publicly accessible database is a huge job, which is why it makes sense to have them pay for it. You'd need lawyers to bless the medical-release forms that would enable the database to obtain your records and to ensure the right privacy-protection mechanisms were in place, nurses or equivalent to interpret the results and convert them from the various lab-specific formats to a uniform representation, statisticians  to determine the analytical models used for prediction and a gaggle of programmers to make it actually work.

The total predictive value of all this data is unknown, precisely because no one has looked. I've never seen a study that tried to assemble all SVR-related factors (the various host factors TN listed) plus  viral factors such as the ISDR sequence of the virus you're carrying, into a comprehensive model and assess its predictive power. It may well be that even though we don't yet understand the biological mechanism of tx success/failure we have identified enough of the asssociated factors to be able to predict outcome with some accuracy, This will never happen as long as we continue to throw away most of the information content of the available data - as in the crude VL cutoffs TN mentioned. The most likely abusers of such a database would not be the drug companies but insurance companies and government-funded health plans. If your predicted chances of success are low enough they probably wouldn't give you the chance to try.

[cbee]

Has anyone had experience with testing negative for cryo and then testing positive?  For years it was negative and then positive again which helped me decide to tx.  Now I'm at 19/24 and I test negative again.  The doctors don't have straight answers.  Does the cryo actually go away?  The doctors tell me once you are positive, you can have false negatives.  Anyone have some good insight into this?

-cbee