Aa
polymerase vs protease inhibitors
Hi Folks, Sorry I haven't been posting. Been gone and off on other tangents a lot recently.
I am starting to get some buzz from my connections for clinical trials. They haven't yet told me what's up, but I can tell that they are gearing up for something that I would qualify for as a non responder. They know I will only do protease inhibitors because of 2 failed attempts with combo. The only protease inhibitor trials I know of in my area are sch503034 and vx950. Sch503034 will not go into phase 3 until much later this year and vx950 is only doing tx naive. So, as best I can tell that leaves only the polymerase inhibitor nm283. I haven't been following this drug. The best info I can find on it was just released from a phase 2b showing good results, but nothing like the early reports on vx950 and sch503034.
Since it seems I will likely be invited to a trial of nm283, does anyone have some advice on choosing this route instead of waiting a year for one of the protease inhibitors. I would jump on the chance for a trial with one of the protease inhibitors, but I don't know much about nm283, so I'm not sure.
I have a 0-1 biopsy, but am quite sick with the HCV. I cannot do another failed attempt for several reasons. I do appreciate any and all feedback on choosing nm283 soon, instead of waiting for the others.
Thanks much,
Rossman
I am starting to get some buzz from my connections for clinical trials. They haven't yet told me what's up, but I can tell that they are gearing up for something that I would qualify for as a non responder. They know I will only do protease inhibitors because of 2 failed attempts with combo. The only protease inhibitor trials I know of in my area are sch503034 and vx950. Sch503034 will not go into phase 3 until much later this year and vx950 is only doing tx naive. So, as best I can tell that leaves only the polymerase inhibitor nm283. I haven't been following this drug. The best info I can find on it was just released from a phase 2b showing good results, but nothing like the early reports on vx950 and sch503034.
Since it seems I will likely be invited to a trial of nm283, does anyone have some advice on choosing this route instead of waiting a year for one of the protease inhibitors. I would jump on the chance for a trial with one of the protease inhibitors, but I don't know much about nm283, so I'm not sure.
I have a 0-1 biopsy, but am quite sick with the HCV. I cannot do another failed attempt for several reasons. I do appreciate any and all feedback on choosing nm283 soon, instead of waiting for the others.
Thanks much,
Rossman
Cuteus quotes a study: "The rates of commonly reported adverse events were the similar for patients whether they received 48 or 72 weeks therapy. Serious adverse events were 5% for 48 weeks & 8% for 72 weeks. There were no previously unreported AEs.
=====================================================
Logic aside -- and logic dictates that the longer you're on these drugs NOT the better -- many of the shorter-course studies suggest the opposite of what you quote above.
One example is from the European short-course study:
"...for patients who become HCV RNA negative at week 4, treatment for 24 weeks has similar high efficacy with superior safety compared to 48 week therapy."
=====================================================
Logic aside -- and logic dictates that the longer you're on these drugs NOT the better -- many of the shorter-course studies suggest the opposite of what you quote above.
One example is from the European short-course study:
"...for patients who become HCV RNA negative at week 4, treatment for 24 weeks has similar high efficacy with superior safety compared to 48 week therapy."
I find this thread very amusing, as it seems some have the opinion that they have a magic looking glass into what works for what genotype with regard to treating HCV.Bottom line is for those individuals who are or considering treatment. The sucess rate will either be 100%, or 0%. That I can guarantee.At this day and age anything else if fluff. For a layman to sit and read abstracts on HCV treatment and thus try to attempt to re-distribute this info to us may be thrilling for a few, but really only serves the distributor. There are a few studies that may suggest this or that, but at the end of the day, each person is an individual and thus using these abstracts to try to predict success or the lack of success is a fool
(A) JmJm said initially:"While some will disagree, my take is that MH, compared to other boards, has a pro-treatment bias in the sense that tx sides/risks are minimized in the risk/reward tx equation.."
(B)Cuteus responds: "members stating their personal experiences and those of the folks with similar experiences of mild to moderate side effects on tx, should not be considered "minimizing tx side effects". They are stating a fact as it pertains to them. If it is to be considered "minimizing", then folks stating how much they ache and how they have to spend 24/7 on the couch, are, by the same token, "maximizing" the effects of tx."
----------------------------------------------------
Wow. Can you please tell me how "B" follows "A" ???
I was clearly talking about treatment bias on the board in terms of advice/opinions/analysis, etc, and in NOT in any way inferring that people are either either "minimizing" or "maximizing" their individual treatment experiences. I value everyone's personal experience at face value and hope others do as well.
(B)Cuteus responds: "members stating their personal experiences and those of the folks with similar experiences of mild to moderate side effects on tx, should not be considered "minimizing tx side effects". They are stating a fact as it pertains to them. If it is to be considered "minimizing", then folks stating how much they ache and how they have to spend 24/7 on the couch, are, by the same token, "maximizing" the effects of tx."
----------------------------------------------------
Wow. Can you please tell me how "B" follows "A" ???
I was clearly talking about treatment bias on the board in terms of advice/opinions/analysis, etc, and in NOT in any way inferring that people are either either "minimizing" or "maximizing" their individual treatment experiences. I value everyone's personal experience at face value and hope others do as well.
members stating their personal experiences and those of the folks with similar experiences of mild to moderate side effects on tx, should not be considered "minimizing tx side effects". They are stating a fact as it pertains to them. If it is to be considered "minimizing", then folks stating how much they ache and how they have to spend 24/7 on the couch, are, by the same token, "maximizing" the effects of tx. same equation. If sides were been minimized here, why are there so many freaked out about tx?
the fact that geno 2 and 3 only have to treat 24 wks, does not benefit the so call risk/reward ratio. Susceptible individuals can have severe adverse effects the first two months of tx. So, stating that it makes sense to offer tx to one genotype and not the other because one only does 24 wks and thus has less chance of severe effects is misleading. I do believe it has to do with cost, the same reason they want to cut the tx in Europe. MONEY.
If length of tx is the factor that weighs on the risk factor, why is it not manifested in these extended tx studies?
"ADVERSE EVENTS
The rates of commonly reported adverse events were the similar for patients whether they received 48 or 72 weeks therapy. Serious adverse events were 5% for 48 weeks & 8% for 72 weeks. There were no previously unreported AEs.
TREATMENT DISCONTINUATION
At week 24, disct was 12% in 72 week grp & 11% in the 48 week grp, the same. At week 48, disct was 18% in the 48 week grp 7 27% in the 72 week grp. And at week 72 the disct rate was 36%."
treatment was discontinued the same for both the 48 group as the 72 group at wk 24. You can make a correlation on the 24 and 48 group with these numbers, can you?
the fact that geno 2 and 3 only have to treat 24 wks, does not benefit the so call risk/reward ratio. Susceptible individuals can have severe adverse effects the first two months of tx. So, stating that it makes sense to offer tx to one genotype and not the other because one only does 24 wks and thus has less chance of severe effects is misleading. I do believe it has to do with cost, the same reason they want to cut the tx in Europe. MONEY.
If length of tx is the factor that weighs on the risk factor, why is it not manifested in these extended tx studies?
"ADVERSE EVENTS
The rates of commonly reported adverse events were the similar for patients whether they received 48 or 72 weeks therapy. Serious adverse events were 5% for 48 weeks & 8% for 72 weeks. There were no previously unreported AEs.
TREATMENT DISCONTINUATION
At week 24, disct was 12% in 72 week grp & 11% in the 48 week grp, the same. At week 48, disct was 18% in the 48 week grp 7 27% in the 72 week grp. And at week 72 the disct rate was 36%."
treatment was discontinued the same for both the 48 group as the 72 group at wk 24. You can make a correlation on the 24 and 48 group with these numbers, can you?
Most report the stats that 5-20% of HCV sufferers will advance to cirrohis. And out of these 5-20%, 1-5% will go on to develope HCC. My math isn't that great today but overall that means about 5 out of every 10,000 to about 20 out of 10,000. The average age of these HCC sufferers are just about 8 years less than the average lifespan today. Scare tactics work on both sides. Peace
I hesitate to say this, but I think ecconomic costs must be recognized too. My doc talks about this openly, and I appreciate his candor. When we speak of me treating for 48 vs. 24 weeks, there is a significant ecconomic differential between the two, and it would be irresponsible not to consider it.
Most of us use insurance to pay for our treatments. Insurance funds are a means of pooling and sharing risks across a population. The funds must be spent judiciously, or in addition to escalating insurance premiums, we risk insolvency of the fund. Meaning no more insurance for the membership.
Back to my case, between the primary and support drugs I'm on, my treatment costs are running somewhere around $2,500 a week. Extending my treatment by 24 weeks carries a significant ecconomic burden. I believe it would be irresponsible for the Doc not to consider that in his decision making process.
Most of us use insurance to pay for our treatments. Insurance funds are a means of pooling and sharing risks across a population. The funds must be spent judiciously, or in addition to escalating insurance premiums, we risk insolvency of the fund. Meaning no more insurance for the membership.
Back to my case, between the primary and support drugs I'm on, my treatment costs are running somewhere around $2,500 a week. Extending my treatment by 24 weeks carries a significant ecconomic burden. I believe it would be irresponsible for the Doc not to consider that in his decision making process.
People should be scared of treatment, very scared. Because my QOL had suffered tremendeously and I was having classic symptoms of advanced liver disease, I felt I had to give tx a shot. Otherwise TX scares me more than HCV, just my personal opinion. Peace
Zero or one hundred percent is the only medically proven effect from interferon treatments to date. If you are suggesting, and I will use your "cure" word for effect, that one can achieve any other result, as one may be 38% cured, or achieve a 68% SVR. Please by all means enlighten us.
Is this "American Idol" or "Survivor". Just wondering as it may or may not influence my vote. This I can be either 100% or 0% sure of. Peace
Oh well, intolerant one, the reality is most know the outcomes, and no doubt can cite them in their sleep. Pompous and arogant, is close to the only opinion that may have any relation to anything. I would suggest that I may be 48% arrogant and close to 28% pompous, but then again only on days when the sun is shining. My next comment I will reduce in scope while retaining the essential elements or abridge for your reading pleasure.
I would check your depends as they seem a mite wet.
I would check your depends as they seem a mite wet.
Goof: If your cognitive function has decreased on treatment treatment as you suggest, it must have been pretty scary good pre-tx. I didn't even know where to begin with that last post after I got to the "The sucess rate will either be 100%, or 0%. That I can guarantee." Boy, if that's what any of my doctors told me I'd be out the door in a second.
Cuteus: You can always poll the audience.
Cuteus: You can always poll the audience.
it is about time we get with the program. Salaries and trial subjetcs re-imbursement must be lower in the old country.
I like playing elitist medical wanna be, I have a couple of lifelines I can use too.
I like playing elitist medical wanna be, I have a couple of lifelines I can use too.
<i>I find this thread very amusing</i>
And I find your pompous arogance pretty amusing too. Between the two of us, we've got a veritable comedy fest going on! Let's enjoy it while it lasts!
<i>ensure that their Doc fully <a href="http://wordnet.princeton.edu/perl/webwn?s=abridge">abridge</a> them of the risks</i>
Thats the exact problem I've been trying to discuss.
<i>The sucess rate will either be 100%, or 0%....anythng else [is] fluff. </i>
Great, so we are to embark upon this treatment not considering probale outcomes, but rather based on a "might work, might not" assessment?
<i>There are a few studies that may suggest this or that, but at the end of the day, each person is an individual and thus using these abstracts to try to predict success or the lack of success is a fool
And I find your pompous arogance pretty amusing too. Between the two of us, we've got a veritable comedy fest going on! Let's enjoy it while it lasts!
<i>ensure that their Doc fully <a href="http://wordnet.princeton.edu/perl/webwn?s=abridge">abridge</a> them of the risks</i>
Thats the exact problem I've been trying to discuss.
<i>The sucess rate will either be 100%, or 0%....anythng else [is] fluff. </i>
Great, so we are to embark upon this treatment not considering probale outcomes, but rather based on a "might work, might not" assessment?
<i>There are a few studies that may suggest this or that, but at the end of the day, each person is an individual and thus using these abstracts to try to predict success or the lack of success is a fool
From one armchair clinician to another with way too much time on our hands :) --
I was referring the fact that one of the conclusions was "superior safety" with the short-course treatment and not making a case for or against it in terms of efficacy -- the study does that for itself. :) BTW when Googling recently to try and pull the study up, I noticed a couple of trials -- not Italians -- not French -- not Spanish -- but AMERICAN trials. So hopefully, more data on shorter treatment courses will be available one of these days.
I was referring the fact that one of the conclusions was "superior safety" with the short-course treatment and not making a case for or against it in terms of efficacy -- the study does that for itself. :) BTW when Googling recently to try and pull the study up, I noticed a couple of trials -- not Italians -- not French -- not Spanish -- but AMERICAN trials. So hopefully, more data on shorter treatment courses will be available one of these days.
we are comparing tx efficacy with tx adverse events, not the same animal, different markings. The study that involved 500 subjects stated that the rate of events was the same in both the 48 wks and 72 wks tx groups. Nothing was said as to efficacy.
Briefly regarding doctors generally recommending geno 2's and 3's treating...
It's the risk/reward equation which basically is at the heart of all medical decisions.
Geno 2's and 3's have an 80% chance of being cured with only 24 weeks of treatment. Therefore their chance of reward (SVR) is greater and their risk (exposure to tx drugs) is less.
Geno 1's, on the other hand, have let's say 40-45% chance of being cured with 48 weeks of treatment. Their chance of reward (SVR) is less and their risk (exposure to tx drugs) is more.
I really think it's only that and to me it makes a lot of sense. I agree that hep c patients should be given all options when diagnosed but a good doctor also has an obligation to explain the options in terms of risk/reward based on his/her knowledge, available studies, and personal clinical findings.
--Jim
It's the risk/reward equation which basically is at the heart of all medical decisions.
Geno 2's and 3's have an 80% chance of being cured with only 24 weeks of treatment. Therefore their chance of reward (SVR) is greater and their risk (exposure to tx drugs) is less.
Geno 1's, on the other hand, have let's say 40-45% chance of being cured with 48 weeks of treatment. Their chance of reward (SVR) is less and their risk (exposure to tx drugs) is more.
I really think it's only that and to me it makes a lot of sense. I agree that hep c patients should be given all options when diagnosed but a good doctor also has an obligation to explain the options in terms of risk/reward based on his/her knowledge, available studies, and personal clinical findings.
--Jim
Awww, c'mon Kalio, no need to get your knickers in a knot - I meant no harm...
You say: <i>I didn't say risks should not be presented openly and honestly
anywhere in my post!</i>
I suppose I could go down the tit-for-tat road and point out that nowhere in my post did I say that you said that in your post. But endlessly listing things we didn't say would probably become counter productive, sooner rather than later :) :)
You say:<i> nor did I say that fear of treatment is
overblown on this board, <b>I said to do so wouldn't be prudent</b>.</i>
Respectfully, I didn't find the words <i>wouldn't be prudent</i> in your post. I did find the quote: <i>...to overblow the fear of lingering long term side effects <b>scares</b> people off from treating</i>
Absent of a conditional modifier such as <i>could</i>, <i>would</i>, or <i>might</i>, I took <b>scares</b>
to imply people are actively being scared off of treating. If that was not your message, my mistake. And since I seem to have missinterpreted your message, where such statements (that didn't occur) were (not) made becomes somewhat moot.
<i>I don't understand what it is you are trying to disagree with me on.</i>
I'm really not. Simply trying to give another point of view. As I said, no harm intended. Sorry that I've offended.
Take care my friend.
You say: <i>I didn't say risks should not be presented openly and honestly
anywhere in my post!</i>
I suppose I could go down the tit-for-tat road and point out that nowhere in my post did I say that you said that in your post. But endlessly listing things we didn't say would probably become counter productive, sooner rather than later :) :)
You say:<i> nor did I say that fear of treatment is
overblown on this board, <b>I said to do so wouldn't be prudent</b>.</i>
Respectfully, I didn't find the words <i>wouldn't be prudent</i> in your post. I did find the quote: <i>...to overblow the fear of lingering long term side effects <b>scares</b> people off from treating</i>
Absent of a conditional modifier such as <i>could</i>, <i>would</i>, or <i>might</i>, I took <b>scares</b>
to imply people are actively being scared off of treating. If that was not your message, my mistake. And since I seem to have missinterpreted your message, where such statements (that didn't occur) were (not) made becomes somewhat moot.
<i>I don't understand what it is you are trying to disagree with me on.</i>
I'm really not. Simply trying to give another point of view. As I said, no harm intended. Sorry that I've offended.
Take care my friend.
I think that there ARE people who come in and read and DO get scared from treating. I know one person who is now petrified of Riba and won't treat because of all they have read.
BUT...like any message board - this board is a hodgepodge of ALL thoughts and opinions and nothing more. Experiences are all different and presented by what the opinion is.
Hopefully we are a good enough example of the positivity of treatment - and can encourage people who need to.
I would never want to turn anyone OFF of tx - people need to decide either way for themselves and we can only give our experiences and advice and opinion on that.
Yeah..we put poisons IN but hopefully they are killing the potentially deadly virus that is already there.
BUT...like any message board - this board is a hodgepodge of ALL thoughts and opinions and nothing more. Experiences are all different and presented by what the opinion is.
Hopefully we are a good enough example of the positivity of treatment - and can encourage people who need to.
I would never want to turn anyone OFF of tx - people need to decide either way for themselves and we can only give our experiences and advice and opinion on that.
Yeah..we put poisons IN but hopefully they are killing the potentially deadly virus that is already there.
See I think that people come in to the forums with pretty much ONE thing on their minds - HOW MUCH IS THE SIDE EFFECTS GOING TO HURT ME????? I know it seems when new people come in my take is that is their first and biggest concern.
What I was trying to SAY is that I would not want to turn anybody off to trying tx based on my whining (ah the anemia is horrible! ah the Ribarash drives me nuts!!!). While I do feel we NEED a place to complain to those who UNDERSTAND...I try to remember that others might see it as IMPOSSIBLE to deal with and choose not to based on my comments.
So I try to remain upbeat about it. It is everyones personal decision in the end. I just don't want to be the cause of mistakenly having anyone think it's not worth trying...just because it IS inconvenient at times.
What I was trying to SAY is that I would not want to turn anybody off to trying tx based on my whining (ah the anemia is horrible! ah the Ribarash drives me nuts!!!). While I do feel we NEED a place to complain to those who UNDERSTAND...I try to remember that others might see it as IMPOSSIBLE to deal with and choose not to based on my comments.
So I try to remain upbeat about it. It is everyones personal decision in the end. I just don't want to be the cause of mistakenly having anyone think it's not worth trying...just because it IS inconvenient at times.
NY said:I would never want to turn anyone OFF of tx - people need to decide either way for themselves and we can only give our experiences and advice and opinion on that.
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Can't agree more on that people need to decide for themselves. However, we have to keep in mind that agressively shepherding people toward treatment who may have other options, is as risky as turning people off treatment who may need it.
While some will disagree, my take is that MH, compared to other boards, has a pro-treatment bias in the sense that tx sides/risks are minimized in the risk/reward tx equation.
Hopefully, those making treatment decisions will carefully read both sets of opinions here, do their own independent research, visit other hep c discusion groups for their perspective -- and of utmost importance -- find the right doctor (preferably a liver specialist (hepatologist) -- who can help put everything together, and guide them toward the right decision for that particular individual.
-- Jim
---------------------------------------------------
Can't agree more on that people need to decide for themselves. However, we have to keep in mind that agressively shepherding people toward treatment who may have other options, is as risky as turning people off treatment who may need it.
While some will disagree, my take is that MH, compared to other boards, has a pro-treatment bias in the sense that tx sides/risks are minimized in the risk/reward tx equation.
Hopefully, those making treatment decisions will carefully read both sets of opinions here, do their own independent research, visit other hep c discusion groups for their perspective -- and of utmost importance -- find the right doctor (preferably a liver specialist (hepatologist) -- who can help put everything together, and guide them toward the right decision for that particular individual.
-- Jim
Here is a study I haven't ever heard of before. I thought some of you might like to read about it.
http://www.romark.com/index.php/media_center/press_releases/35.html
Monte
http://www.romark.com/index.php/media_center/press_releases/35.html
Monte
My ANC (absolute neutrophils) have been as low as 320. My med team rarely uses Neupogen and only if it drops to around 200. BTW they are VERY agressive, just not with this drug. Everytime I got below 500, I emailed them and they told me to relax, that it will probably bounce back it -- that the low count was probably caused by an infection. They were right. My ANC has "bounced" around from 320 to 1700 often in a matter of weeks. Currently it's around 1200. My opinion -- and it's only that -- is that most doctors are too slow on the draw with Procrit but too fast on the draw with Neupogen. Again, unlike with Hgb, ANC can reverse itself very quickly without a rescue drug. Your milage may vary but I certainly wouldn't be concerned at ANC 1000.
-- Jim
-- Jim
Hi Land,
Lessee LOL..
Seriously, I read your post to define EVR as non-detectible at week 24, but yes, what you say here, is correct -- a two-log or better drop at week 12 is EVR. Better of course is being non-detectible at week 12.
One reason the more sensitive tests are better is because non-detectible is more and more being defined by the studies as at least under 50 IU/ml. So, if your test has a sensitivity of 600 IU/ml, you could test negative but still be detectible, if say your viral load was 400 IU/ml.
So, using the Drusano model (treat 36 weeks past non-detectible) using a less sensitive test could result in a different tx length. As another example, if you went non-detectible at week 4, and were having a very difficult period with sides at week 4, you would have more information to make a decision regarding the risks/rewards of continuing on. Lastly, multiple PCR's have the added benefit of more or less guaranteeing you that you were consistently negative throughout treatment. It's possible some people have a viral breakthrough -- then a reversal -- mid treatment and don't know it. If they had the added information, they might treat longer.
That said, testing at week 12, 24 and 48 is pretty standard with the 4-week PCR becoming more popular. I'd simply recommend that as long as you're getting stuck with the needle, why not get the most sensitive test available?
It's a bit past my bedtime, so I hope this is making some sense.
Take care and thanks for asking.
-- Jim
Lessee LOL..
Seriously, I read your post to define EVR as non-detectible at week 24, but yes, what you say here, is correct -- a two-log or better drop at week 12 is EVR. Better of course is being non-detectible at week 12.
One reason the more sensitive tests are better is because non-detectible is more and more being defined by the studies as at least under 50 IU/ml. So, if your test has a sensitivity of 600 IU/ml, you could test negative but still be detectible, if say your viral load was 400 IU/ml.
So, using the Drusano model (treat 36 weeks past non-detectible) using a less sensitive test could result in a different tx length. As another example, if you went non-detectible at week 4, and were having a very difficult period with sides at week 4, you would have more information to make a decision regarding the risks/rewards of continuing on. Lastly, multiple PCR's have the added benefit of more or less guaranteeing you that you were consistently negative throughout treatment. It's possible some people have a viral breakthrough -- then a reversal -- mid treatment and don't know it. If they had the added information, they might treat longer.
That said, testing at week 12, 24 and 48 is pretty standard with the 4-week PCR becoming more popular. I'd simply recommend that as long as you're getting stuck with the needle, why not get the most sensitive test available?
It's a bit past my bedtime, so I hope this is making some sense.
Take care and thanks for asking.
-- Jim
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