Aa
HR, extremely disturbed about this "tapering" off INF theory recently posted
I just read the post about tapering off interferon in order to allow for ones own immune system to re-adjust in order to suppress any remainding viral particles. I firmly believe that is why I didn't have an SVR after 72 weeks of trteatment, as well as the two previous times treating. The reason I feel this way is due to fact that when I finally stopped after 72+ weeks I could actually feel my own immune system "coming back online". Within the first few days I had frequent bouts of fever and sweating. It is also interesting to note that within that first week off the drugs I was experiencing alot of personal stress with loved ones and I now theorize this stress hindered my innate immune system from "mopping up" any latent viral particles. I 'm feeling angry and disgusted with the incompetence of most doctors for not recognizing this simple principle of immune system re-adjustment and viral re-bound.
and as you should be along with about 15 others on this forum who have relapsed after 24, 48 and 72 weeks of pure hell only to be tripped up by simple common since “fact” that what ever goes up has got to come down.
Here is a condensed recap of the thread.
***Would like to hear from some of these folks and at what point did they relapse and possible symptoms…***
for the last 6month and she tapered off the IFN slowly at the end, no abrupt stopping.
if you don’t mind answering or know the reason why Kalio tapered off the Interferon and not abruptly stop at the end of TX as one would normally with SOC? Any insight would be much appreciated.
The registration trials stop IFN abruptly, because it is too difficult to monitor the tapering down of IFN.
SOC mimicks the trials.
With IFN, like any other drug , the body gets used to it, it becomes part of the daily complex immune cell signaling equilibrium. Immune dampening mechanisms are activated at the same time, to prevent immune activation "runaway".
When you abruptly stop it , the increased immune activity will , for a while, swing below its normal equilibirum, generating a temporary state of lowered anti HCV activity - like taking "anti-Interferon". This will give HCV remnants a better chance to resurface, while the antiviral activity/defense is exceptional low.
Ribavirin tapers off "naturally", because it has such a long half life.
HR could you tell me how long Kalio took tapering off the interferon? I am looking forward to ending 72 weeks of treatment in about 6 weeks. Also I have been on procrit. Should I taper off that as well? thanks for communicating with Kalio for us.
6 to 8 weeks of careful tapering is what you might want to discuss with your doc. Procrit does not seem to be directly related to anti HCV activity, and the riba wears slowly off by itelf.
HR--I'm curious as to your opinion of tapering off the peg towards end of treatment, as well as the opposite- increasing peg towards end of treatment. I drew the 72 week tx straw. To complete my tx I have been given 4 peginton redipens @ 150, but my rx is for 120, so was told to dial down the redipen to the #4 setting....Do you see any benefit to taking the full 150 dose for my last 4 shots? Do you see any benefit to reducing peg dosage towards eot? Thanks for any opinion you may offer..
proactive
(I read what you posted to geter, could you elaborate a bit more if possible?)
Thank you for answering my long standing question and a follow through question from oceanliver. Combined they answered the questions I have had about EOT and tapering off of the meds as in reverse of dosing up in the beginning of TX. The Riba I understood but the Interferon I was unsure of and what effects it would have or play when stopping suddenly at the end of tx and what effects it would have on the immune system as well as the rest of the body. I will follow my plan at the end of TX and that is to taper off the interferon over the next four weeks after completing the 48 weeks and hopefully head off any addition sx on the post side of the treatment.
(I probably should have started a new thread) I see you may have answered some of my questions in previous posts, but again if you would care to expand this discussion that would be great...I also read what you wrote about the riba, long half life, kinda self tapering..What about those on high dose riba (21mg/kg/day), should one toy with the idea of tapering down to typical weight based towards end of treatment? (I originally started at 1200mg/day-stats in profile)
Thanks (this tapering thing really interests me as well, are there any studies available?)
I am not aware of any tapering comparative studies. these studies are very expensive and unless you have fairly high numbers of participants ( the "powering" of the study) you can end up having "no statistically significant effect", despite the fact that there is indeed a real effect.
It is just an obvious fact that abruptly stopping IFN will put you in a temporary state of reduced antiviral immune defense ( below our "off IFN normal"). The actual time course and reduction speed - the tapering gradient- is therefore up to the doc that understands that concept.
When "SOC" for HCV was 3 times 3 Million units of IFN alpha /wk, some smart hepatologists realized, that it is a better idea, not to let the virus bounce back every second day, producing a seasaw curve of VL reduction. They prescribed off label daily IFN, with dramatically bettter SVr rates. Lucky patients who had these wise hepatologist in these early days.
So what I think your saying and from what I’ve gathered from reading numerous post over the past 39 weeks is that the body produces interferon on it’s own but not enough to completely fight off the overwhelming advance of the Hepc replication overtime and thus adapts and manipulates its environment in order to survive. (sorry laymen terms). Thus when dosing up to a higher level than the body can produce a RVR (in most cases) is achieved and the follow up of maintenance or remaining weeks of SOC is to get any virons that got away or have been split apart by the (inf, riba or combination of both) and floating freely with in the body.
Now at the EOT, theaters stop abruptly per present protocol and the body goes into shock (basically) because the immune system has adapted to the higher level of INF and all the sudden it stops and then the immune systems, dampening / activation are in a battle to right the ship so to speak and when these swings are happening there are periods when these free floating split up virons that are undetected by any blood test have that small window in which to reassemble and start reproducing the same or off springs on the low side where as a relapse will occur in the 3, 6 and one year time frame.
But, by tapering off the interferon over a period of time it will allow the bodies own natural immune system to achieve its own equilibrium in a timely step down fashion or closer to it before being cut off completely with out allowing the window of opportunity for anti-Interferon to occur with in the system thus reducing the chances even further of re-replication.
I understand that there are many variables to this straight line of thinking on my part BUT if the relapse rates start to increase, as with many people here and in trial studies would there not be more effort placed on exploring a taper off period at the end of treatment from a study point of view?
I had ask my doc. on the last visit about this same thing (tapering off the meds) and he looked at me and said, It’s like grandmas chicken soup (no pun intended ladies) when you start adding a little extra of this and a little of that it’s not grandmas chicken soup anymore. Duh!
The way you decribed it is quite adequate. Some common sense measures will not be proved in trials. Trials are to get a substance approved, and then there are small variation trials, that universities do in their own hospitals.
Here is a condensed recap of the thread.
***Would like to hear from some of these folks and at what point did they relapse and possible symptoms…***
for the last 6month and she tapered off the IFN slowly at the end, no abrupt stopping.
if you don’t mind answering or know the reason why Kalio tapered off the Interferon and not abruptly stop at the end of TX as one would normally with SOC? Any insight would be much appreciated.
The registration trials stop IFN abruptly, because it is too difficult to monitor the tapering down of IFN.
SOC mimicks the trials.
With IFN, like any other drug , the body gets used to it, it becomes part of the daily complex immune cell signaling equilibrium. Immune dampening mechanisms are activated at the same time, to prevent immune activation "runaway".
When you abruptly stop it , the increased immune activity will , for a while, swing below its normal equilibirum, generating a temporary state of lowered anti HCV activity - like taking "anti-Interferon". This will give HCV remnants a better chance to resurface, while the antiviral activity/defense is exceptional low.
Ribavirin tapers off "naturally", because it has such a long half life.
HR could you tell me how long Kalio took tapering off the interferon? I am looking forward to ending 72 weeks of treatment in about 6 weeks. Also I have been on procrit. Should I taper off that as well? thanks for communicating with Kalio for us.
6 to 8 weeks of careful tapering is what you might want to discuss with your doc. Procrit does not seem to be directly related to anti HCV activity, and the riba wears slowly off by itelf.
HR--I'm curious as to your opinion of tapering off the peg towards end of treatment, as well as the opposite- increasing peg towards end of treatment. I drew the 72 week tx straw. To complete my tx I have been given 4 peginton redipens @ 150, but my rx is for 120, so was told to dial down the redipen to the #4 setting....Do you see any benefit to taking the full 150 dose for my last 4 shots? Do you see any benefit to reducing peg dosage towards eot? Thanks for any opinion you may offer..
proactive
(I read what you posted to geter, could you elaborate a bit more if possible?)
Thank you for answering my long standing question and a follow through question from oceanliver. Combined they answered the questions I have had about EOT and tapering off of the meds as in reverse of dosing up in the beginning of TX. The Riba I understood but the Interferon I was unsure of and what effects it would have or play when stopping suddenly at the end of tx and what effects it would have on the immune system as well as the rest of the body. I will follow my plan at the end of TX and that is to taper off the interferon over the next four weeks after completing the 48 weeks and hopefully head off any addition sx on the post side of the treatment.
(I probably should have started a new thread) I see you may have answered some of my questions in previous posts, but again if you would care to expand this discussion that would be great...I also read what you wrote about the riba, long half life, kinda self tapering..What about those on high dose riba (21mg/kg/day), should one toy with the idea of tapering down to typical weight based towards end of treatment? (I originally started at 1200mg/day-stats in profile)
Thanks (this tapering thing really interests me as well, are there any studies available?)
I am not aware of any tapering comparative studies. these studies are very expensive and unless you have fairly high numbers of participants ( the "powering" of the study) you can end up having "no statistically significant effect", despite the fact that there is indeed a real effect.
It is just an obvious fact that abruptly stopping IFN will put you in a temporary state of reduced antiviral immune defense ( below our "off IFN normal"). The actual time course and reduction speed - the tapering gradient- is therefore up to the doc that understands that concept.
When "SOC" for HCV was 3 times 3 Million units of IFN alpha /wk, some smart hepatologists realized, that it is a better idea, not to let the virus bounce back every second day, producing a seasaw curve of VL reduction. They prescribed off label daily IFN, with dramatically bettter SVr rates. Lucky patients who had these wise hepatologist in these early days.
So what I think your saying and from what I’ve gathered from reading numerous post over the past 39 weeks is that the body produces interferon on it’s own but not enough to completely fight off the overwhelming advance of the Hepc replication overtime and thus adapts and manipulates its environment in order to survive. (sorry laymen terms). Thus when dosing up to a higher level than the body can produce a RVR (in most cases) is achieved and the follow up of maintenance or remaining weeks of SOC is to get any virons that got away or have been split apart by the (inf, riba or combination of both) and floating freely with in the body.
Now at the EOT, theaters stop abruptly per present protocol and the body goes into shock (basically) because the immune system has adapted to the higher level of INF and all the sudden it stops and then the immune systems, dampening / activation are in a battle to right the ship so to speak and when these swings are happening there are periods when these free floating split up virons that are undetected by any blood test have that small window in which to reassemble and start reproducing the same or off springs on the low side where as a relapse will occur in the 3, 6 and one year time frame.
But, by tapering off the interferon over a period of time it will allow the bodies own natural immune system to achieve its own equilibrium in a timely step down fashion or closer to it before being cut off completely with out allowing the window of opportunity for anti-Interferon to occur with in the system thus reducing the chances even further of re-replication.
I understand that there are many variables to this straight line of thinking on my part BUT if the relapse rates start to increase, as with many people here and in trial studies would there not be more effort placed on exploring a taper off period at the end of treatment from a study point of view?
I had ask my doc. on the last visit about this same thing (tapering off the meds) and he looked at me and said, It’s like grandmas chicken soup (no pun intended ladies) when you start adding a little extra of this and a little of that it’s not grandmas chicken soup anymore. Duh!
The way you decribed it is quite adequate. Some common sense measures will not be proved in trials. Trials are to get a substance approved, and then there are small variation trials, that universities do in their own hospitals.
Do you have a source for the tappering off theory (sorry, I missed the other thread wherever it is). I am approaching 48 weeks (41 right now) - it would be appealing to reduce the interferon dose over the last few weeks before finish.
There's a difference between "tapering" off interferon as discussed, and reducing the Peg, as in your case. Tapering has not be trialed as far as I know. Peg reductions have been chronicled and best results are still from full dose. If Tapering is done, I assume it is done at the end of treatment and not part of it. By this I mean is that if 48 weeks has been calculated for treatment length -- then one would start to taper at week 49. Otherwise, in effect, you would be cutting treatment short.
-- Jim
-- Jim
Thanks Jim - I doubt I could get insurance to tapper off post 48 weeks, so will stay on regular SOC. Hopefully will work out well as I was RVR - just getting nervous now, which is normal in the 40's I am guessing.
I was wonder about you as well… Another question would be if the Interferon has bulked up the immune system beyond the body’s natural equilibrium over an extended period of time what other organs has it affected? Mine would be the Thyroid, first Hyper then Hypo, so what can I look forward to at the end of tx? The same bouncing back and forth as when dosing up, man I hope not because I do not want to go through that again.
jasper
jasper
By all means as jim has mentioned.... AT THE END OF TREATMENT and no where in between with out first consulting with your doctor.
jasper
jasper
Just to be clear, I'm neither endorsing -- nor criticizing -- the taper off approach. Really have no idea as this is in the theoretical plane since no studies exist I'm aware of.
I did grapple with the taper issue myself at the end of treatment, but in the end decided not to monkey around with a formula that seemed to be working so well for me on paper since I was RVR.
I also suppose how much one buys into this theory depends in part on which side of the SVR theory one is on. To vastly oversimply -- for those that believe it's basically the immune system holding the virus 'down' post tx, then it makes more sense to taper. For those (like my doc) that believe the *viable* virus is either gone or not, it probably doesn't, and in fact one might argue to even *hammer* the virus at the very end with more Peg at the very end like one oft quoted internet doc (Dr. C.) has postulated. I don't know what I believe but of course *prefer* to believe that if if the virus is gone, it's gone. Gone, dead, gone, kinda gone :)
-- Jim
I did grapple with the taper issue myself at the end of treatment, but in the end decided not to monkey around with a formula that seemed to be working so well for me on paper since I was RVR.
I also suppose how much one buys into this theory depends in part on which side of the SVR theory one is on. To vastly oversimply -- for those that believe it's basically the immune system holding the virus 'down' post tx, then it makes more sense to taper. For those (like my doc) that believe the *viable* virus is either gone or not, it probably doesn't, and in fact one might argue to even *hammer* the virus at the very end with more Peg at the very end like one oft quoted internet doc (Dr. C.) has postulated. I don't know what I believe but of course *prefer* to believe that if if the virus is gone, it's gone. Gone, dead, gone, kinda gone :)
-- Jim
I'm starting to wonder if maybe that 48 weeks may not even needed. What I mean is that if as soon as one registers undetecatble what if one theoretically started to taper down over maybe a few months. This would make sense if indeeed the immune system is only taking over after treatment to keep the virus suppressed. How else can you explain someone like myself treating for 72 weeks with high dose riba and still failing to respond?
This is a very interesting concept.... I stopped on a dime, but did not have a feeling of my immune system struggling. I was juat so happy to have survived that maybe I just didn't notice. hope many chime in.
Why don't you try and be a guinea pig? We will all watch. I hope it works for you, but per jmjm530's logic which makes sense to me, I have my doubts (I probably have the "virus gone" view, not because I have knowledge, just I like the idea).
"Moa" is right. Anything is possible, but you would be a real guinea pig to do as you suggest.
As to your question, a detailed breakdown of your viral kinectics (if available) as well as other stats, might tell the story, or it may not, as so much is still not understood how this virus works and how it gets killed off.
As to your question, a detailed breakdown of your viral kinectics (if available) as well as other stats, might tell the story, or it may not, as so much is still not understood how this virus works and how it gets killed off.
You know the more I contemplate this issue the more it makes logical sense. Since this virus multiplies at a phenomenol rate, it then makes sense that when the host becomes infected, the immune system becomes overwhelmed and can't keep up with this new burden. So, what happens is the body goes into survival mode and does its best at keeping the viral load down as much as possible. When we take the immununolgical drugs we beat the virus down to so-called "un-detectable levels". When the treatment has ended our body, if lucky , can now keep the few latent or hidden virions under control,not unlike the Herpes virus, before it has a chance to again propagate. I am surely going to taper off months in advance this time around. I wonder if I may have had the coveted Sustained Viral Response my first treatment instaed of my now upcoming fourth. This really makes me mad! Also, another thought to ponder is when the small percentage of people who clear on their own in the acute phase is this because the viral pool is still small in number and the persons immune system is in the TH1 driven mode( TH1 look it up) and can easily wipe the virus out or at least suppress it to undetectable levels? Is it that for us who become chronic is it because our immune systems are imbalanced and skue towards the TH2 side of immunity? Things to ponder.
Interesting idea that brings to mind other ideas. IF some insurance companies were to only allow so much product (in Moa's case or other geno 1's- 48 weeks) would there be a better way to spend or allocate the drugs? I don't have the trial at my fingertips but there are several trials that suggested that higher dosing in the initial 4 weeks increased the response rate in co-infected HCV-HIV patients.
Logic tells you that the last few doses might provide less antiviral activity than the first several weeks.
Since the same dynamic occurs in many other drugs it would seem reasonable to assume it could also happen with interferon as well. If so......are there tests in which one could gauge the bodies return to self sufficiency in redeveloping immune response? IF there are markers then one could possibly tailor a tapering off period. Could some judicious use of the same amount of dosing provide equal or increased response rate?
These theories make my head hurt a little. On one hand we are being asked to believe that the virii become interferon resistant. Is there an implication of tapering off TX? I believe that with antibiotics they NEVER want you to taper off the drug since it does encourage resistance.
(by the way; Good luck Moa)
best,
Willy
Logic tells you that the last few doses might provide less antiviral activity than the first several weeks.
Since the same dynamic occurs in many other drugs it would seem reasonable to assume it could also happen with interferon as well. If so......are there tests in which one could gauge the bodies return to self sufficiency in redeveloping immune response? IF there are markers then one could possibly tailor a tapering off period. Could some judicious use of the same amount of dosing provide equal or increased response rate?
These theories make my head hurt a little. On one hand we are being asked to believe that the virii become interferon resistant. Is there an implication of tapering off TX? I believe that with antibiotics they NEVER want you to taper off the drug since it does encourage resistance.
(by the way; Good luck Moa)
best,
Willy
Willy: ......are there tests in which one could gauge the bodies return to self sufficiency in redeveloping immune response?
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I think you hit it on the head here. When trying to decide whether or not to extend, my tx doctor told me that the only way to be 100% sure would be if I could be tested to see if my tx-induced t-cell response was a durable response. He suggested this was possible in theory but no tests available in practice. If/when such a test becomes available, then the guesswork out of "when to stop" should be taken out of the equation.
--------------------------------------------------------------------
I think you hit it on the head here. When trying to decide whether or not to extend, my tx doctor told me that the only way to be 100% sure would be if I could be tested to see if my tx-induced t-cell response was a durable response. He suggested this was possible in theory but no tests available in practice. If/when such a test becomes available, then the guesswork out of "when to stop" should be taken out of the equation.
There are currently T-cell as well as Nk (natural killer cell ) tests available which measure the rise and fall of these cells. HIV patients use them frequently to gauge their immune fitness I believe.
It would be great if more research money went into such tests, but I doubt the profit potential/motivation is anywhere near as great as that a new 'wonder' drug would bring.
Yeah, I’ve been kinda sick the past 40 weeks “O” and am still wondering if it’s gone. Man, you covered all the bases on that one. LOL!
But I’m sure everyone will come to their own conclusion or at least a thought of, around week 35 after being through hell as to what is best for them at the end of TX. I am glad it was brought up by a notable researcher with more in depth knowledge and hands on aspects of the nitty gritty of hepc treatments for which my lingering questions have been answered as with a few others.
Cheers!
Jasper
But I’m sure everyone will come to their own conclusion or at least a thought of, around week 35 after being through hell as to what is best for them at the end of TX. I am glad it was brought up by a notable researcher with more in depth knowledge and hands on aspects of the nitty gritty of hepc treatments for which my lingering questions have been answered as with a few others.
Cheers!
Jasper
and by no means was the last post any slant towards you. Your contributions have been and are a grounding base for lots of folks coming here for good solid information.
jasper
jasper
I don't think I understood your last post enough to be affected either way :) I thought we were in agreement per your post before this one. Was there something I said after you want to put up for discussion?
-- Jim
-- Jim
Meant to say "per two posts ago" where you said
"By all means as jim has mentioned.... AT THE END OF TREATMENT and no where in between with out first consulting with your doctor."
Sounded to me like we were/are on the same page?
"By all means as jim has mentioned.... AT THE END OF TREATMENT and no where in between with out first consulting with your doctor."
Sounded to me like we were/are on the same page?
No, we are in total agreement about “no where in between” with out consulting with the doc.
But after posting and re-reading the “”But I’m sure everyone will come to their own conclusion or at least a thought of, around week 35 after being through hell as to what is best for them at the end of TX. I am glad it was brought up by a notable researcher with more in depth knowledge and hands on aspects of the nitty gritty of hepc treatments for which my lingering questions have been answered as with a few others.””
I thought it came across a little snubbing sarcastic or maybe it’s just the morning after meds messing with me, can't keep that jasper locked up all the time, LOL! Nuff said.
jasper
But after posting and re-reading the “”But I’m sure everyone will come to their own conclusion or at least a thought of, around week 35 after being through hell as to what is best for them at the end of TX. I am glad it was brought up by a notable researcher with more in depth knowledge and hands on aspects of the nitty gritty of hepc treatments for which my lingering questions have been answered as with a few others.””
I thought it came across a little snubbing sarcastic or maybe it’s just the morning after meds messing with me, can't keep that jasper locked up all the time, LOL! Nuff said.
jasper
Got it. Thanks for clarifying. However, not sure that HR has advocated tapering off before SOC is finished, if that is what you inferred. Actually don't know one way or another. In Kalio's case, she was well beyond SOC before she started the taper.
-- Jim
-- Jim
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