Aa
Stopping tx 12-16 weeks
My Hepatologist feels I could probably stop at 12-16 weeks. I am a geno2 ...had the disease for 33 yrs. If I am UND at 4 weeks this is the plan.
Do you think it's wise to stop that soon? Why do most 2's do the 24 week tx?
Julia
Do you think it's wise to stop that soon? Why do most 2's do the 24 week tx?
Julia
Some comments:
The randomisation in the Berg-study was unusual: The patients were adjusted to the groups before start of therapy, not depending from PCR results of week 12. In addition, the dosis of ribavirin was low. Today Berg would use a different study design, I am sure.
The steps 24-48-72 are very simple and do not reflect the individual situation, as mentioned by Jim. But who should pay for e.g. 96 weeks and who could stand two years of treatment without a brake? My idea for people with slow response and more bad factors of prognosis would be to go 72 weeks of SOC and ADD 24 weeks of a low dose interferon monotherapy. The body has to change physiology from external IFN to own production from one day to another after 72 weeks. Does this give the few persisting viral copies the chance to strong up? A low dose therapy with mono IFN could add some “pressure” on the dragon without being too bad for the patient and the wallet.
Just an idea and not proven in studies, or is there any experience with it?
Writing this, the next question comes up: What about interferon resistance, does it exist? Would it be an argument not to continue with IFN and wait for better drugs after relaps?
Hmm.
drofi
The randomisation in the Berg-study was unusual: The patients were adjusted to the groups before start of therapy, not depending from PCR results of week 12. In addition, the dosis of ribavirin was low. Today Berg would use a different study design, I am sure.
The steps 24-48-72 are very simple and do not reflect the individual situation, as mentioned by Jim. But who should pay for e.g. 96 weeks and who could stand two years of treatment without a brake? My idea for people with slow response and more bad factors of prognosis would be to go 72 weeks of SOC and ADD 24 weeks of a low dose interferon monotherapy. The body has to change physiology from external IFN to own production from one day to another after 72 weeks. Does this give the few persisting viral copies the chance to strong up? A low dose therapy with mono IFN could add some “pressure” on the dragon without being too bad for the patient and the wallet.
Just an idea and not proven in studies, or is there any experience with it?
Writing this, the next question comes up: What about interferon resistance, does it exist? Would it be an argument not to continue with IFN and wait for better drugs after relaps?
Hmm.
drofi
While it's almost impossible to qualify everything we say here (like your initial charcterization of Drusano IMO) , I thought I was very "clear" (almost tedious) re Drusano (modified Drusano actually) and how it was applied by my doctor in my individual case which was to INCREASE tx time, not decrease it -- and indeed it seems to be supported by Berg (your post above) for EVRs, which I was (actually RVR). I also have posted numerous times the studies re 72-weeks for geno 1's who were detectible at 12 but non-detectible at 24. Again, these studies (studies in general) don't always match up -- they all have achilles heels, just different ones -- and therefore all tools should be on the table to work with, including Drusano. BTW thanks for offering up the article, but I thought it was the one in German, and given your last quote from the study, it doesn't appear that I have any disagreements with it.
As to your question -- were you an EVR given your 15 IU/ml where -- on one hand it would appear which study you're using. If the study used 10 IU/ml (or less) as a cut-off than you certainly weren't. But I think your question was more where to place yourself if the study used a cut off of let's say 50 IU/ml. The situation here is obviously more cloudy and in lieu of similar studies using more sensitive tests, one might conclude that the subset of those detectible by sensitive TMA (but not detectible by PCR) at week 12, most probably will have higher relapse rates than those non-detectible by TMA, at least given the same tx time. It's possible those figures are broken down somewhere, but maybe not. Again, one limitation of studies, which is matching up a large study group to one individuals's stats.
All the best,
-- Jim
As to your question -- were you an EVR given your 15 IU/ml where -- on one hand it would appear which study you're using. If the study used 10 IU/ml (or less) as a cut-off than you certainly weren't. But I think your question was more where to place yourself if the study used a cut off of let's say 50 IU/ml. The situation here is obviously more cloudy and in lieu of similar studies using more sensitive tests, one might conclude that the subset of those detectible by sensitive TMA (but not detectible by PCR) at week 12, most probably will have higher relapse rates than those non-detectible by TMA, at least given the same tx time. It's possible those figures are broken down somewhere, but maybe not. Again, one limitation of studies, which is matching up a large study group to one individuals's stats.
All the best,
-- Jim
Yes, Jim, I am also living the studies. As you know, I started out with a 70% hope of being an RVR because of my low baseline viral load, only to have to realize that I was a slow responder, detectable at week 12 with a test of the sensitivity of 15 IU/ml. (So was I an EVR or not, being < 50 IU/ml at week 12?) So I, as you, have had my fair deal of struggling with studies and decisions about treatment duration. I have consulted 4 different hepatologists, all with different opinions, and in the end this forum (with the special help of Friole, Nygirl and you) and a family member educated in statistics helped me sort out my thoughts and emotions so that I could make my own treatment decision which has since been approved by my doctor.
I understand the way you and your doctor used the Drusano model, and this seems reasonable to me. I think this is very important for you to point out when you post about this model. I know of my own experience how very tempting any mention of Drusano is to a slow responder. It is IMO important for you to be very clear on how it was used in your case - to add tx duration to the 48 week course, not to shorten the 72 week course.
You certainly do not come off as argumentative. Discussions with people such as you are one of the refreshing elements on this board, which makes our understanding of the fight against this virus increase.
I understand the way you and your doctor used the Drusano model, and this seems reasonable to me. I think this is very important for you to point out when you post about this model. I know of my own experience how very tempting any mention of Drusano is to a slow responder. It is IMO important for you to be very clear on how it was used in your case - to add tx duration to the 48 week course, not to shorten the 72 week course.
You certainly do not come off as argumentative. Discussions with people such as you are one of the refreshing elements on this board, which makes our understanding of the fight against this virus increase.
The Berg study I quoted is the full text study in English from 2006 on extended treatment. If you want to, I can send it to you. (Friole also has it, if you prefer contact with her.) Let me know at my screenname underscorejonesathotmaildotcom.
For your information, I will quote here what more is said in this Berg study about the Drusano model:
"Drusano and Preston recently presented a mathematical model to predict whether patients may achieve SVR or suffer from relapse. It was concluded that type 1-infected patients require the continuous abscence of detectable HCV RNA in serum for 36 weeks to attain 90% probabilities of an SVR (ie, relapse rate of 10%). We agree only to some extent with this predictive model, realizing that our week-12 rapid virologic responders who were HCV-RNA negative for at least 36 weeks also had low relapse rates (< or = 15%). However, group B late responders..."
For your information, I will quote here what more is said in this Berg study about the Drusano model:
"Drusano and Preston recently presented a mathematical model to predict whether patients may achieve SVR or suffer from relapse. It was concluded that type 1-infected patients require the continuous abscence of detectable HCV RNA in serum for 36 weeks to attain 90% probabilities of an SVR (ie, relapse rate of 10%). We agree only to some extent with this predictive model, realizing that our week-12 rapid virologic responders who were HCV-RNA negative for at least 36 weeks also had low relapse rates (< or = 15%). However, group B late responders..."
BTW hope I'm not coming off argumentative on this, but this isn't just an intellectual discussion for me (not that it is for you) because I litterally lived these studies and decisions by reading all pertinent studies and discussing with at least six hepatologists (3 in personal consultation). Where I came out -- and I'm sure I'm not alone here -- is that the study data are just jumping off guidelines -- be it the formal studies or mathematical models like Drusano -- but often things then have to be tweaked, analyzed and in a sense guessed (educated hopefully) over for the final decision. Or, you can do what probably the majority of patients do and that is do exactly what your doctor says :)
-- Jim
-- Jim
Zazza: We need guidelines to go by, and at present the consensus among hepatologists seems to be leaning more and more towards: Detectable at week 12, UND at week 24, go the full 72 week course.
------------------------------------------------------------
Yes, and that particular study trumps Drusano IMO, as I've stated many times before. However, the way my doc and NP applied Drusano was different, as I was non-detectible before week 12.
Can't really comment too much more on Berg, since I assume the study you quote is the one published in German? Hopefully, you or someone else will offer us a translation at some point, so we know what we're discussing. If it's an English article you're quoting, please supply the link.
But going back to my case again -- the only reference I made to Drusano -- that particular study wasn't published as best I know. And even if it was, I wouldn't have qualified for 72 weeks since I was non-detectible at week 6. So what my doc did was the opposite of your reasonable concern. He didn't use Drusano to shorten my treatment, but he used a variation of Drusano to urge me to treat longer. And the reason this variation of Drusano was used was because there were no studies that matched up to my stats such as "detectable at week 12, UND at week 24...etc. Again, I was RVR but I also was told to hve significant fibrosis plus advanced age. This is where the limitations of the studies are -- no clear match ups -- and this is where the "art" or judgment calls come into play that IMO justify treatment periods between the study guidelines of let's say 48 and 72 weeks, as in my case and in others.
All the best,
-- Jim
------------------------------------------------------------
Yes, and that particular study trumps Drusano IMO, as I've stated many times before. However, the way my doc and NP applied Drusano was different, as I was non-detectible before week 12.
Can't really comment too much more on Berg, since I assume the study you quote is the one published in German? Hopefully, you or someone else will offer us a translation at some point, so we know what we're discussing. If it's an English article you're quoting, please supply the link.
But going back to my case again -- the only reference I made to Drusano -- that particular study wasn't published as best I know. And even if it was, I wouldn't have qualified for 72 weeks since I was non-detectible at week 6. So what my doc did was the opposite of your reasonable concern. He didn't use Drusano to shorten my treatment, but he used a variation of Drusano to urge me to treat longer. And the reason this variation of Drusano was used was because there were no studies that matched up to my stats such as "detectable at week 12, UND at week 24...etc. Again, I was RVR but I also was told to hve significant fibrosis plus advanced age. This is where the limitations of the studies are -- no clear match ups -- and this is where the "art" or judgment calls come into play that IMO justify treatment periods between the study guidelines of let's say 48 and 72 weeks, as in my case and in others.
All the best,
-- Jim
To me the danger with the Drusano model is that it is very tempting for the slow responders to just add 36 weeks to the week they become UND. And it is precisely the slow responders who need to calculate their treatment length in "a more exponential way".
Quote from "Extended Treatment Duration for Hepatitis C Virus Type 1: Comparing 48 Versus 72 Weeks of Peginterferon-Alfa-2a Plus Ribavirin" by Berg et al, concerning the Drusano model:
"However, group B late responders who first became HCV-RNA negative at week 24 (ie, who also had undetectable HCV-RNA levels during the last 36 weeks of the total 72-week treatment period) still had relapse rates of 40%, a finding that clearly contradicts the proposed Drusano and Preston model. Obviously, the HCV-RNA negative phase required to prevent a relapse must be calculated in a more exponential way and seems to be dependent on how early a patient becomes HCV-RNA negative during treatment."
Of course you are correct that having treated long enough one can become virus free at any week, not just at week 48 or 72. But when is "long enough" for a particular patient? We need guidelines to go by, and at present the consensus among hepatologists seems to be leaning more and more towards: Detectable at week 12, UND at week 24, go the full 72 week course.
Quote from "Extended Treatment Duration for Hepatitis C Virus Type 1: Comparing 48 Versus 72 Weeks of Peginterferon-Alfa-2a Plus Ribavirin" by Berg et al, concerning the Drusano model:
"However, group B late responders who first became HCV-RNA negative at week 24 (ie, who also had undetectable HCV-RNA levels during the last 36 weeks of the total 72-week treatment period) still had relapse rates of 40%, a finding that clearly contradicts the proposed Drusano and Preston model. Obviously, the HCV-RNA negative phase required to prevent a relapse must be calculated in a more exponential way and seems to be dependent on how early a patient becomes HCV-RNA negative during treatment."
Of course you are correct that having treated long enough one can become virus free at any week, not just at week 48 or 72. But when is "long enough" for a particular patient? We need guidelines to go by, and at present the consensus among hepatologists seems to be leaning more and more towards: Detectable at week 12, UND at week 24, go the full 72 week course.
The slow responder who decides to go past the 48 week mark but treats for less than 72 weeks and then relapses, will always have the question unanswered, what if I had done the full course?
That is correct, the Drusano model is a mathematical model built on accumulated data. Be clear that I did not suggest anyone used it to determine treatment length -- I mentioned studies for that -- but simply reported that my doctor -- a leading hepatologist -- as well as my NP, referenced it in my treatment and we ended up using a modified version (my doc thought it didn't apply to me because of age and histology) in my individual case. I have also read here that a couple of other very well-known hepatologists have also used Drusano as a GUIDE to determine treatment length. To say it is "dangerous" in influencing your opinion IMO is an overstatment, unless you mean using it as the sole influence. Unfortunately no science yet in predicting optimum tx length and we have to use as many tools at our disposal -- studies, anecdotal data in the field, and models like Drusano -- to come up with something that makes sense for a given individual. The fact that there haven't been any studies to back up tx lengths between 48 and 72 weeks doesn't mean that someone in conjunction with their doc, can decide that treating within that frame isn't reasonable. When we treat successfully for 72 weeks, I would imagine in most cases that doesn't mean that the virus is still going strong at 71 weeks.
-- Jim
-- Jim
-- Jim
-- Jim
Notice that it is called the Drusano MODEL. It is a mathematical model, not supported by studies, and, in my opinion, letting it influence your decision of the length of your tx is dangerous.
Studies I have read make me support the criteria PSP-n-Me's clinic has regarding geno 1:
RVR (UND by week 4), low VL, low liver damage - possible to consider 24 weeks tx
EVR (UND by week 12) - 48 weeks tx
Detectable by week 12, UND by week 24 - 72 weeks
There has, to my knowledge, been no studies to back up treatments of any length between 48 and 72 weeks.
Studies I have read make me support the criteria PSP-n-Me's clinic has regarding geno 1:
RVR (UND by week 4), low VL, low liver damage - possible to consider 24 weeks tx
EVR (UND by week 12) - 48 weeks tx
Detectable by week 12, UND by week 24 - 72 weeks
There has, to my knowledge, been no studies to back up treatments of any length between 48 and 72 weeks.
Hi there - Nice to see you :)
The Clinic I go has a totally differnt approach to the "36 week rule" they now use, as standard practice, RVR 24 weeks for 1's - if not clear by 12 weeks then it's 72 weeks for 1's and 48 for 2's
But, that said - there is certain critieria for shortened treatment of 1's - you have to have low VL (under 600K) low liver damage (no higher than a stage 1 - they do not consider grade anymore)
I think the times, they are a changing *dip*
The Clinic I go has a totally differnt approach to the "36 week rule" they now use, as standard practice, RVR 24 weeks for 1's - if not clear by 12 weeks then it's 72 weeks for 1's and 48 for 2's
But, that said - there is certain critieria for shortened treatment of 1's - you have to have low VL (under 600K) low liver damage (no higher than a stage 1 - they do not consider grade anymore)
I think the times, they are a changing *dip*
Last paragraph a little unclear. Left out that the Drusano model predicts around 80% SVR if you add 36 weeks. The 70% figure was if you add 24 weeks. This is all by memory and may be off a little, so please check from the source if interested. Also, when I said my NP would let me off in 36 weeks, I wasn not referring to Drusano, but to 36 weeks of total treatment.
One last thing and hopefully I'll stick to it :) In regard to my six week extension. Besides my docs opinion -- and his anecdotal accounts of significant relapse per cents in his practice in older patients -- I was unable to find a study which I could break down into a subset of older patients with Fibrosis who were RVR. Just couldn't find it which is often the case. This therefore left enough doubt in my mind (with of course my docs position) to err on the side of extending a little. It was a difficult decision and somewhat of a compromise, and looking back it still seems reasonable although my hunch is I would have SVR'd with 48 weeks, no problem.
-- Jim
-- Jim
Drofi, Thanks for the post.
CS, yes it's all in the details and hopefully anyone following this will see how important it is to get access to a full-text study (as opposed to abstract) when treatment decisions are going to be in part based on the study. Even looking at the same study in its entirety it's easy to see how different overall conclusions can be made and phrased. A couple of the charts really break things down to help match ups, and the overall conclusions are well hedged depending on individual factors such as pre-tx viral load (where <400,000 actually shows higher VL for the low dose group) plus the ribavirin issue is discussed, but IMO not convincingly although the authors do say more study needed. Still, the trend among the better hepatologists I'm familiar with is to treat geno 2's and 3's with weight base.
I won't do a line-by-line on your previous post other than to say we're in agreement more than not. But I will answer two of your questions/comments re my own treatment.
CS: Clear at 6 weeks is not RVR
---------------------------------------------
It depends on your definition of RVR and what tests you took. For example, if RVR is defined by a study as <50 IU/ml, and you are 25 at wk 4 (using a test with sensitivity of 5) then you are not non-detectible (clear) at week 4 but you are RVR. Or are you? And how many of the "RVRs" per study would have been truly non-dectible with a test sensitive to 5?
My case was even less clear because I was tested weekly from week 1 and was below 50 at week 3 (RVR right?) BUT above 50 at week 4 (when the study would test), even higher at week 5, but under 5 (non-detectible) at week 6. So tell me, was I RVR or not :) Well, no clear guidelines but the consensus of my docs is that I was, also factoring in a week of stopping riba around week 2-3 due to anemia from high doses or riba (2000 mg/day).
CS: You will have to tell me how hou came up with 54 weeks.
-----------------------------------------------------------------------------------
Yes, given my RVR (or even EVR), 48 weeks by most studies should have done it, but at that time (and I'm sure my doc still thinks this way) some very good docs were pushing for more time for those with significant liver damage. My doc felt that given my age (58) and histology, I needed more time than the studies suggested. Being who he was (a guy who does many of the major studies) and the fact that he probably treats more patients than a lot of these studies combined represent, I did factor in his opinion heavily even though two other equally well-versed docs said 48 weeks would be enough.
As stated before the actual number (my doc probably would hv been happier with 60 or even 72 weeks) came from a variation of the Drusano model formula.
Drusano says add 36 weeks (or 24 for I think 70% chance of SVR) to the date you were non-detectible. My doc felt that 48 weeks is more appropriate (at a minimum) to those older and with more fibrosis than represented by the Drusano group. His NP btw felt 48 weeks was fine, in fact given my RVR (and also the fact that my seven day drop was just about two logs) she probably would have let me off treatment in 36 weeks had I pushed for it. She clearly believes and has stated that from her observations, early response is the single most important factor in determining SVR.
Thanks for the discussion.
All the best,
-- Jim
CS, yes it's all in the details and hopefully anyone following this will see how important it is to get access to a full-text study (as opposed to abstract) when treatment decisions are going to be in part based on the study. Even looking at the same study in its entirety it's easy to see how different overall conclusions can be made and phrased. A couple of the charts really break things down to help match ups, and the overall conclusions are well hedged depending on individual factors such as pre-tx viral load (where <400,000 actually shows higher VL for the low dose group) plus the ribavirin issue is discussed, but IMO not convincingly although the authors do say more study needed. Still, the trend among the better hepatologists I'm familiar with is to treat geno 2's and 3's with weight base.
I won't do a line-by-line on your previous post other than to say we're in agreement more than not. But I will answer two of your questions/comments re my own treatment.
CS: Clear at 6 weeks is not RVR
---------------------------------------------
It depends on your definition of RVR and what tests you took. For example, if RVR is defined by a study as <50 IU/ml, and you are 25 at wk 4 (using a test with sensitivity of 5) then you are not non-detectible (clear) at week 4 but you are RVR. Or are you? And how many of the "RVRs" per study would have been truly non-dectible with a test sensitive to 5?
My case was even less clear because I was tested weekly from week 1 and was below 50 at week 3 (RVR right?) BUT above 50 at week 4 (when the study would test), even higher at week 5, but under 5 (non-detectible) at week 6. So tell me, was I RVR or not :) Well, no clear guidelines but the consensus of my docs is that I was, also factoring in a week of stopping riba around week 2-3 due to anemia from high doses or riba (2000 mg/day).
CS: You will have to tell me how hou came up with 54 weeks.
-----------------------------------------------------------------------------------
Yes, given my RVR (or even EVR), 48 weeks by most studies should have done it, but at that time (and I'm sure my doc still thinks this way) some very good docs were pushing for more time for those with significant liver damage. My doc felt that given my age (58) and histology, I needed more time than the studies suggested. Being who he was (a guy who does many of the major studies) and the fact that he probably treats more patients than a lot of these studies combined represent, I did factor in his opinion heavily even though two other equally well-versed docs said 48 weeks would be enough.
As stated before the actual number (my doc probably would hv been happier with 60 or even 72 weeks) came from a variation of the Drusano model formula.
Drusano says add 36 weeks (or 24 for I think 70% chance of SVR) to the date you were non-detectible. My doc felt that 48 weeks is more appropriate (at a minimum) to those older and with more fibrosis than represented by the Drusano group. His NP btw felt 48 weeks was fine, in fact given my RVR (and also the fact that my seven day drop was just about two logs) she probably would have let me off treatment in 36 weeks had I pushed for it. She clearly believes and has stated that from her observations, early response is the single most important factor in determining SVR.
Thanks for the discussion.
All the best,
-- Jim
Thanx, wondered how i was going to lay my hands on it.
A little strange that the stats are slightly different than the ones publised in abstarct form.
CS
A little strange that the stats are slightly different than the ones publised in abstarct form.
CS
You are not wrong about the full text articles.
This clearly shows the diffences and similarites between G2s and 3s
Enjoyed this chat.
CS
This clearly shows the diffences and similarites between G2s and 3s
Enjoyed this chat.
CS
Here is a download link for the full text NEJM paper about the Accelerate study:
http://hepatitis-rm.de/downloads/Studie2007.pdf
drofi
http://hepatitis-rm.de/downloads/Studie2007.pdf
drofi
Must be this para it hates.
With the low svr rates for patients who didn’t RVR in Accelerate trial , the Pegasys insert studies 4&5 were re evaluated to see if 48 weeks made any difference. It most definitely did, went from <50% to 76%. Add this to High relapse rates and the logic is sound.
With the low svr rates for patients who didn’t RVR in Accelerate trial , the Pegasys insert studies 4&5 were re evaluated to see if 48 weeks made any difference. It most definitely did, went from <50% to 76%. Add this to High relapse rates and the logic is sound.
Must be something in this para that it doesnt like. Try again
Once again, The following comes from the CIGNA HEALTHCARE COVERAGE POSITION
patients with genotype 3 who have steatosis and initial high viral loads (HCV RNA >600,000 IU/mL) receive therapy for 48 weeks.
Why would they pay for this if it didn’t make any difference? For the love of Interferon.
Once again, The following comes from the CIGNA HEALTHCARE COVERAGE POSITION
patients with genotype 3 who have steatosis and initial high viral loads (HCV RNA >600,000 IU/mL) receive therapy for 48 weeks.
Why would they pay for this if it didn’t make any difference? For the love of Interferon.
Somehow these two paras got messed up, so i'll post again
With the low svr rates for patients who didn’t RVR in Accelerate trial , the Pegasys insert studies 4&5 were re evaluated to see if 48 weeks made any difference. It most definitely did, went from 600,000 IU/mL) receive therapy for 48 weeks.
Why would they pay for this if it didn’t make any difference? For the love of Interferon.
CS
With the low svr rates for patients who didn’t RVR in Accelerate trial , the Pegasys insert studies 4&5 were re evaluated to see if 48 weeks made any difference. It most definitely did, went from 600,000 IU/mL) receive therapy for 48 weeks.
Why would they pay for this if it didn’t make any difference? For the love of Interferon.
CS
I agree i wouldnt accept RVR if the test was >10IU. The lower the better. 600IU would have too high a chance of relapse if used as decision tool for shortening Tx.
One other thing UND at 6 weeks in not RVR for any geno. Just a very early EVR.
CS
One other thing UND at 6 weeks in not RVR for any geno. Just a very early EVR.
CS
Forgot to mention in the Get-C study everyone will receive WB Riba (800-1200mg) and 1.5ug PegIntron.
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
