Aa
New Approach for Treatment
As some of you know, I've been trying to get a "compassionate use" approval through both the FDA and Vertex for the VX-950 protease inhibitor. The road has been long, going back and forth with the FDA as to exactly how to fill out the paperwork, with the doctor finally sending all the paperwork to the FDA tomorrow. He will also contact Vertex once the FDA gives their approval. I will post the results.
My Gastro has a plan, and I would like to know if anyone else has heard of or has tried this approach:
When I finally get the VX-950 (or something else), he first wants to double dose me with Pegasys and raise the Riba to 15mg daily from 12mg. His train of thought is that if and when we bring the viral count down enough, then we introduce the protease inhibitor.
This seems like a enigmatic move to me, but he has given it a lot of thought. Now, I would like to get your thoughts on this type of approach. Naturally, he said it was up to me. He also said that if I don't drop the viral load soon after the double dosing, he would go back to standard dosing and the protease inhibitor. He plans blood work every two weeks to be sure I'm not being killed. In case you don’t know, I’m a four time non-responder.
What do you tink?
Magnum
My Gastro has a plan, and I would like to know if anyone else has heard of or has tried this approach:
When I finally get the VX-950 (or something else), he first wants to double dose me with Pegasys and raise the Riba to 15mg daily from 12mg. His train of thought is that if and when we bring the viral count down enough, then we introduce the protease inhibitor.
This seems like a enigmatic move to me, but he has given it a lot of thought. Now, I would like to get your thoughts on this type of approach. Naturally, he said it was up to me. He also said that if I don't drop the viral load soon after the double dosing, he would go back to standard dosing and the protease inhibitor. He plans blood work every two weeks to be sure I'm not being killed. In case you don’t know, I’m a four time non-responder.
What do you tink?
Magnum
MerryBe wrote-
Now, I discussed this myself with my liver clinics NP and she told me
why this was not a good idea. To quote her "every transfusion reduces your chance of having a successful transplant. Should treatment fail, and you were to need a transplant, every transfusion will have created so many antibodies (to another's blood) that the imune system will be seriously messed up." She said "the rate of organ rejection in those transfused 2 or more times is much much higher than for those never transfused".
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Magnum - thank you so much for sharing your situation and please continue to keep us informed with your progress on treatment.
Two years ago i consulted with Dr. Everson, chairman of a transplant committee. I received about 150 transfusions in the 1981, which we talked about. We also spoke about the possibility of a transplant. He wanted to know about my support systems, spouse, family etc. No mention was made about transfusions causing any problems. Can anyone confirm that previous transfusions can cause problems as MB states? Thank you.
eric
in any case, saying I make stuff up is like calling me a liar Jim...is that your intent?
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It was more sarcasm than accusation. But I do think it irresponsible to make claims like you have with being able to back it up with a study and that is not being sarcastic.
It was not the Lindahl study as you initially stated so specifically before
MB: "Riba on the other hand (in Karen Lindahl;s study had everyone SVRing...but a 20% kidney failure. Somewhere in the SOC range lies sanity."
Nor do I believe it was in any study based on everything I have read. If you post the study I will be happy to admit I am wrong but in the meanwhile it might be more responsible to check your facts first. My guess is that your recollection is incorrect.
-- Jim
-- Jim
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It was more sarcasm than accusation. But I do think it irresponsible to make claims like you have with being able to back it up with a study and that is not being sarcastic.
It was not the Lindahl study as you initially stated so specifically before
MB: "Riba on the other hand (in Karen Lindahl;s study had everyone SVRing...but a 20% kidney failure. Somewhere in the SOC range lies sanity."
Nor do I believe it was in any study based on everything I have read. If you post the study I will be happy to admit I am wrong but in the meanwhile it might be more responsible to check your facts first. My guess is that your recollection is incorrect.
-- Jim
-- Jim
I've been racking my brain trying to remeber where I read of the increased fibrosis and renal insufficiencies and failures at high dosing...and it's still escaping me,,,although I know I read it somewhere...just like I know somewhere the riba effects on the lungs were compared to the breakdown in cystic fibrosis and that the riba might be altering the genetic coding for lung mucousa the way CF does in some people..
all that said, one thing in the posted link jogged my brain on the other down side to the higher dosings....please note in that study (only one of dozens lindahl has done that I've read, the rate of needed transfusion was at 20%...or 2 out of ten.
why would this also be a concern....well, you are leading into tx with extreme high dosing...the INF and the Riba both contribute to anemia....if that type of dosing tanks you and THEn you hit it with teleprevir known to tank us even worse, the chance exists that not even neupo/epo would your blood come up....in which case you would become one of those who needed transfusing.....and you may need it more than once while on tx if this turn of events occurs.
Now, I discussed this myself with my liver clinics NP and she told me why this was not a good idea. To quote her "every transfusion reduces your chance of having a successful transplant. Should treatment fail, and you were to need a transplant, every transfusion will have created so many antibodies (to another's blood) that the imune system will be seriously messed up." She said "the rate of organ rejection in those transfused 2 or more times is much much higher than for those never transfused".
Now I don't know what study she got this info from, but I heard it with my own ears and have no reasonable reason to doubt her. This was one more reason I choose to go with extending tx but no double dosing.
Just my take on how to access risks, especially when at stage 4.
One thing I not factored in or discussed in this thread, that probably should be looked at, is whether someone would even be a candidate for a transplant.
There are a whole host of reasons why someone might not be a good transplant candidate...age, other health issues like heart problems, coinfection with HIV or even just having a rare blood type would make it unlikely that someone would be approves, or in approved that they would recieve a new liver.
If you happen to be in any category that would preclude transplant, then this might be one reason that a doctor might look at treating the disease more aggressively, and, where that reasoning might retain some merit.
That might be something you would want to be sure a clarify with your doctor for sure.
Many folks treating do not discuss transplant...some do not even know their blood type or if it's rare, There's only a 50/50 shot at best of getting a new organ with the commonist blood group, but chances go down to 5% or less with the rare blood types.
Maybe you might want to talk to Amadio about all this..
He treated successfully with teleprevir after several attempts with SOC were unsuccessful.
Maybe talking to those for whom normal doses did the trick with the Vertex might help you in weighing whether to DD and if so, how much is really safe.
I don't believe he DD/d or preloaded and he still beat it.....that should give you some real hope. feel free to PM me if you need or want any private support.
mb
all that said, one thing in the posted link jogged my brain on the other down side to the higher dosings....please note in that study (only one of dozens lindahl has done that I've read, the rate of needed transfusion was at 20%...or 2 out of ten.
why would this also be a concern....well, you are leading into tx with extreme high dosing...the INF and the Riba both contribute to anemia....if that type of dosing tanks you and THEn you hit it with teleprevir known to tank us even worse, the chance exists that not even neupo/epo would your blood come up....in which case you would become one of those who needed transfusing.....and you may need it more than once while on tx if this turn of events occurs.
Now, I discussed this myself with my liver clinics NP and she told me why this was not a good idea. To quote her "every transfusion reduces your chance of having a successful transplant. Should treatment fail, and you were to need a transplant, every transfusion will have created so many antibodies (to another's blood) that the imune system will be seriously messed up." She said "the rate of organ rejection in those transfused 2 or more times is much much higher than for those never transfused".
Now I don't know what study she got this info from, but I heard it with my own ears and have no reasonable reason to doubt her. This was one more reason I choose to go with extending tx but no double dosing.
Just my take on how to access risks, especially when at stage 4.
One thing I not factored in or discussed in this thread, that probably should be looked at, is whether someone would even be a candidate for a transplant.
There are a whole host of reasons why someone might not be a good transplant candidate...age, other health issues like heart problems, coinfection with HIV or even just having a rare blood type would make it unlikely that someone would be approves, or in approved that they would recieve a new liver.
If you happen to be in any category that would preclude transplant, then this might be one reason that a doctor might look at treating the disease more aggressively, and, where that reasoning might retain some merit.
That might be something you would want to be sure a clarify with your doctor for sure.
Many folks treating do not discuss transplant...some do not even know their blood type or if it's rare, There's only a 50/50 shot at best of getting a new organ with the commonist blood group, but chances go down to 5% or less with the rare blood types.
Maybe you might want to talk to Amadio about all this..
He treated successfully with teleprevir after several attempts with SOC were unsuccessful.
Maybe talking to those for whom normal doses did the trick with the Vertex might help you in weighing whether to DD and if so, how much is really safe.
I don't believe he DD/d or preloaded and he still beat it.....that should give you some real hope. feel free to PM me if you need or want any private support.
mb
nope sorry, I don't make things up.
I'm sorry for the way I worded this fact though, what I should have said is that at the highest doses ONLY used in one study (an effective double dose) the rate of kidney failure was 2 out of ten people. That means the higher doses are very dangerous, and not just because of kidneys failure, but because the higher doses can also impair kidney function permanently. Ribivarin is known to cause kidney fibrosis, especially at high dosages, and the sense in trying to cure a fibrotic liver at the expense of making your kidneys fibrotic escapes me.
now you will ask me where I read this, and to be honest, I'm not sure.
I read extensively inpubmed, several hundred studies this year alone...
There are well over 700 studies on ribivirin and it's effects on the kidneys alone, and if I stumble across where I read it, I'll be happy to post it, but I don't have a photographic memory anymore...I thought it was the lindahl study, but it appears it may not have been.I spent 30 minutes trying to find it before giving up
In any case, there is more to double dosing than meets the eye. In Japan they now adjust peoples Riba based on their clearance of the same...
in any case, saying I make stuff up is like calling me a liar Jim...is that your intent?
mb
I'm sorry for the way I worded this fact though, what I should have said is that at the highest doses ONLY used in one study (an effective double dose) the rate of kidney failure was 2 out of ten people. That means the higher doses are very dangerous, and not just because of kidneys failure, but because the higher doses can also impair kidney function permanently. Ribivarin is known to cause kidney fibrosis, especially at high dosages, and the sense in trying to cure a fibrotic liver at the expense of making your kidneys fibrotic escapes me.
now you will ask me where I read this, and to be honest, I'm not sure.
I read extensively inpubmed, several hundred studies this year alone...
There are well over 700 studies on ribivirin and it's effects on the kidneys alone, and if I stumble across where I read it, I'll be happy to post it, but I don't have a photographic memory anymore...I thought it was the lindahl study, but it appears it may not have been.I spent 30 minutes trying to find it before giving up
In any case, there is more to double dosing than meets the eye. In Japan they now adjust peoples Riba based on their clearance of the same...
in any case, saying I make stuff up is like calling me a liar Jim...is that your intent?
mb
Magnum, you seem to be on the right track.
Nice to have Dr Gish on your case.
You can just feel the vast hepatic experience of Dr Gish just oozing out of that letter. Sweet !
best of luck to ya
apache
Nice to have Dr Gish on your case.
You can just feel the vast hepatic experience of Dr Gish just oozing out of that letter. Sweet !
best of luck to ya
apache
This is a letter my Hepatologist Dr. Robert Gish wrote to my former Gastroenterologist (who I recently saw for yet another opinion). That Gastro, which I call Dr. Doom, had a very dark outlook on my condition, which prompted me to contact Dr. gish for his take on what the Gastro said.
Below is the letter he wrote him, with a copy sent to me. In case you don't know, Dr. Gish is a world renowned Hepatologist and the director of liver transplants for the West Coast. In other words, his words in my opinion, carry a lot of weight. Read and digest what he says, and please give me your take....
Magnum
Patient contacted me about his Hepatitis C and Cirrhosis status. I have not received any labs since last July 2008 except alpha-fetoprotein that is borderline elevated in the 30 range. The patient is to have standard liver cancer surveillance every six months, and has had an abdominal ultrasound in December 2008 that showed two cysts, no evidence of cancer, large spleen.
As you know, last summer the patient had normal INR, normal platelet count, CPT score of 5, MELD score 7. Thus his chances of dying in the next 12 months due to liver failure, when looking albumin of 3.9 and bilirubin 1, are probably under 3%. I think his 5 year chance of needing a liver transplant or developing liver cancer is in the 20% range.
The patient is not showing any current signs of liver failure, but I will be obtaining all current lab tests and dictations from your office. The patient should be on standard lab tests at least every six months, noting also in February 2009, he had a Bilirubin 1.0, albumin 3.7, platelet count 84,000.
I think there is a very high probability the patient will be able to survive for the next three years until the Vertex drug is available. The phase III studies with Vertex are completely filled and enrolled. The next opportunity for obtaining Vertex unless they roll out the compassionate use protocol, I think is minimal.
At that time, we will be treating patients with tripple therapy for 8-12 weeks, then dual therapy for a minimum of 12 weeks in my opinion. Any further questions please contact my office.
Robert Gish, MD
Medical Director
Liver Transplant Program
Below is the letter he wrote him, with a copy sent to me. In case you don't know, Dr. Gish is a world renowned Hepatologist and the director of liver transplants for the West Coast. In other words, his words in my opinion, carry a lot of weight. Read and digest what he says, and please give me your take....
Magnum
Patient contacted me about his Hepatitis C and Cirrhosis status. I have not received any labs since last July 2008 except alpha-fetoprotein that is borderline elevated in the 30 range. The patient is to have standard liver cancer surveillance every six months, and has had an abdominal ultrasound in December 2008 that showed two cysts, no evidence of cancer, large spleen.
As you know, last summer the patient had normal INR, normal platelet count, CPT score of 5, MELD score 7. Thus his chances of dying in the next 12 months due to liver failure, when looking albumin of 3.9 and bilirubin 1, are probably under 3%. I think his 5 year chance of needing a liver transplant or developing liver cancer is in the 20% range.
The patient is not showing any current signs of liver failure, but I will be obtaining all current lab tests and dictations from your office. The patient should be on standard lab tests at least every six months, noting also in February 2009, he had a Bilirubin 1.0, albumin 3.7, platelet count 84,000.
I think there is a very high probability the patient will be able to survive for the next three years until the Vertex drug is available. The phase III studies with Vertex are completely filled and enrolled. The next opportunity for obtaining Vertex unless they roll out the compassionate use protocol, I think is minimal.
At that time, we will be treating patients with tripple therapy for 8-12 weeks, then dual therapy for a minimum of 12 weeks in my opinion. Any further questions please contact my office.
Robert Gish, MD
Medical Director
Liver Transplant Program
With regard to your treatment progrqamme,I would suggest that you pre-dose ribavirin for four weeks.The role of ribavirin is to insure against relapse by creating genetic sampling error.You will need substantial levels of serum ribavirin by the time the anti-viral therapy hits.
Forget about Lindahl-tiny study,no follow up.
I would like to know what your viralogical response to interferon has been at four weeks hitherto.
If you have achieved 1 log then I would suggest an interferon lead in ,similarly of four weeks intoducing telaprevir in week five.
What interests me more is your history of non-response to interferon.Please could you re-post the data on this.I understand that insulin resistance is not an issue.
Forget about Lindahl-tiny study,no follow up.
I would like to know what your viralogical response to interferon has been at four weeks hitherto.
If you have achieved 1 log then I would suggest an interferon lead in ,similarly of four weeks intoducing telaprevir in week five.
What interests me more is your history of non-response to interferon.Please could you re-post the data on this.I understand that insulin resistance is not an issue.
Thanks. It was clear from your initial post what the intent was and I didn't take that last Lindahl post in any way to suggest is as a route for Magnum.
I thought that I would address the subject of predosing, double dosing etc and just highlight a few ideas that could make higher dosing of riba and perhaps IFN as problematic for a stage 4 on TVR. I made the case for a possible surge or predose in my first post and I saw a few others suggest it as well. I simply thought I would write a little to suggest that it could be a bit edgy while on TVR. I wanted to point out that there was no data on surging/ double dosing with TVR and that it could be potentially a risky thing in Magnum's circumstance.
And so..... my prior post was intended to temper my own remarks; not yours.
best,
Willy
I thought that I would address the subject of predosing, double dosing etc and just highlight a few ideas that could make higher dosing of riba and perhaps IFN as problematic for a stage 4 on TVR. I made the case for a possible surge or predose in my first post and I saw a few others suggest it as well. I simply thought I would write a little to suggest that it could be a bit edgy while on TVR. I wanted to point out that there was no data on surging/ double dosing with TVR and that it could be potentially a risky thing in Magnum's circumstance.
And so..... my prior post was intended to temper my own remarks; not yours.
best,
Willy
Willy: Thank you, by the way Jim for posting the link to the study. It suggests that some higher dosing could be possible but that in turn there needs to be higher monitoring and by knowlegable people
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Hopefully it was clear that the study was not posted in terms of Magnum's or anyone else's treatment, but only to contradict MerrryBe's false statements in her post above.
But as long as you bring it up, the reason riba levels got up slower than expected in the Lindahl study is that the starting dose was sub-optimal per a faulty pharmakentic formula used based on kidney function. That formula may have been corrected later or dumped, really don't know. Pre-dosing is another matter although related in some aspects, but again my entry in this thread was simply to clear up a gross false statement by MerryBe and not to make any treatment suggestions to anyone.
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Hopefully it was clear that the study was not posted in terms of Magnum's or anyone else's treatment, but only to contradict MerrryBe's false statements in her post above.
But as long as you bring it up, the reason riba levels got up slower than expected in the Lindahl study is that the starting dose was sub-optimal per a faulty pharmakentic formula used based on kidney function. That formula may have been corrected later or dumped, really don't know. Pre-dosing is another matter although related in some aspects, but again my entry in this thread was simply to clear up a gross false statement by MerryBe and not to make any treatment suggestions to anyone.
I'm all for a surge of sorts but one must factor in that any of the studies are for SOC; not SOC PLUS TVR. That could be an important difference. Thank you, by the way Jim for posting the link to the study. It suggests that some higher dosing could be possible but that in turn there needs to be higher monitoring and by knowlegable people. I don't know exactly that tipping point where one can "surf" and stay on the edge of high IFN or Riba doing particularly when adding Telaprevir, a drug which can cause a much higher rate of discontinuations.
One must also note that the Lindahl study was small; only 10 people and further and of perhaps great consequence for Magnums purpose it had no stage 4 participants, or no cirrhotics. This could play an important part of this dosing regimen. One wants a good result, but the patient has to be able to tolerate the dosing. This is perhaps a key issue where Magnum treats since he has a meld score. What may work for stage 1, 2 or 3 may not be advisable for him. This is where some smart or experienced doctoring and monitoring will be important. The design itself might also be run by Gish. I have a feeling that high dosing would not be approved by anybody for "compassionate care".
Of note from the study; they spoke that it took some time to get riba concentrations up in the patients. This speaks to me of the need to pre dose the SOC before the TVR is added. I actually thing that the notion of a short riba predose before the IFN might also allow the riba to slowly build without having to resort to higher dosing. It is tempting to try to get the riba dosing HIGH during the initial TVR dosing but there really doesn't exist much data to suggest that this is safe; actually to the contrary, the discontinuation rate suggests that it may not be.
Still rescue drugs need to be on hand at the ready if one decides to try to pull that off BUT......
keep in mind that the highest cause for discontinuation of TVR is RASH. Predosing the riba could accentuate that issue and high dose would likely increase the risk of rash discontinuation further still. The doctor needs to be familiar with any rash and sides management. It will likely be a greater issue for you if you do a lead in, do higher dosing and perhaps because of your staging.
It was for these reasons if there were methods to lower your viral load pre-TX that did not challenge these issues one might more safely be able to use a number of strategies and at different times that could create an improvement without adding much risk since you may be "redlining" it anyway simply doing triple therapy. There aren't a lot of studies which bear exactly on your potential situation.
best,
Willy
One must also note that the Lindahl study was small; only 10 people and further and of perhaps great consequence for Magnums purpose it had no stage 4 participants, or no cirrhotics. This could play an important part of this dosing regimen. One wants a good result, but the patient has to be able to tolerate the dosing. This is perhaps a key issue where Magnum treats since he has a meld score. What may work for stage 1, 2 or 3 may not be advisable for him. This is where some smart or experienced doctoring and monitoring will be important. The design itself might also be run by Gish. I have a feeling that high dosing would not be approved by anybody for "compassionate care".
Of note from the study; they spoke that it took some time to get riba concentrations up in the patients. This speaks to me of the need to pre dose the SOC before the TVR is added. I actually thing that the notion of a short riba predose before the IFN might also allow the riba to slowly build without having to resort to higher dosing. It is tempting to try to get the riba dosing HIGH during the initial TVR dosing but there really doesn't exist much data to suggest that this is safe; actually to the contrary, the discontinuation rate suggests that it may not be.
Still rescue drugs need to be on hand at the ready if one decides to try to pull that off BUT......
keep in mind that the highest cause for discontinuation of TVR is RASH. Predosing the riba could accentuate that issue and high dose would likely increase the risk of rash discontinuation further still. The doctor needs to be familiar with any rash and sides management. It will likely be a greater issue for you if you do a lead in, do higher dosing and perhaps because of your staging.
It was for these reasons if there were methods to lower your viral load pre-TX that did not challenge these issues one might more safely be able to use a number of strategies and at different times that could create an improvement without adding much risk since you may be "redlining" it anyway simply doing triple therapy. There aren't a lot of studies which bear exactly on your potential situation.
best,
Willy
How does your Dr. want you to take the Peg doses...all in one day or divided during the week? How often will he run PCR's in the early weeks?
I doubled the Peg and took 1400 Riba for the first 12 weeks of tx. No major problems til week 10, but didn't get an RVR either. Reached a complete EVR by week 12, then decreased meds to SOC for 3 weeks due to psych issues and anemia. Now up to 270 mcg Peg and 1200 mg Riba. So far, so good.......
The only other suggestion I would offer would be to have labs run weekly especially that first month of DD to keep tabs on sudden drops.
Good luck in whatever you decide.....Pam
I doubled the Peg and took 1400 Riba for the first 12 weeks of tx. No major problems til week 10, but didn't get an RVR either. Reached a complete EVR by week 12, then decreased meds to SOC for 3 weeks due to psych issues and anemia. Now up to 270 mcg Peg and 1200 mg Riba. So far, so good.......
The only other suggestion I would offer would be to have labs run weekly especially that first month of DD to keep tabs on sudden drops.
Good luck in whatever you decide.....Pam
MerryBe: The higher Riba on the other hand (in Karen Lindahl;s study had everyone SVRing...but a 20% kidney failure....
and also read that 1 in 5 with Higher Riba dosing lost a kidney...
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Do you make this stuff up? If not, you would do all of us a service, especially members new here, if you took the time and checked sources before posting nonsense as you do time and time again. The Lindahl study you refer to is below. Please show me where "1 in 5 with higher riba dosing lost a kidney".
http://www3.interscience.wiley.com/cgi-bin/fulltext/109867030/HTMLSTART
and also read that 1 in 5 with Higher Riba dosing lost a kidney...
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Do you make this stuff up? If not, you would do all of us a service, especially members new here, if you took the time and checked sources before posting nonsense as you do time and time again. The Lindahl study you refer to is below. Please show me where "1 in 5 with higher riba dosing lost a kidney".
http://www3.interscience.wiley.com/cgi-bin/fulltext/109867030/HTMLSTART
Yes 12 weeks of Telaprevir in the trial. I do believe I read Andiamo did 6 months Telaprevir. There's another girl on the forum who did 8 weeks of Tela but she doesn't know her results yet.
Another question is how many weeks of Telaprevir they will give you. I believe the Phase 3 trials going on right now are based on a 12 week dosing--please, participants, correct me if I'm wrong.
I am in the Vertex no placebo trial. I was Und and RVR by week 4. I suspect I was und by week 2 as my ast and alt fell in the 20's. It's going to be Telaprevir that knocks the virus down quickly. At 10 weeks I had to do a Riba reduction ( 1000mg to 600mg ) due to low hgb so make sure you have access to rescue drugs. Telaprevir also causes your hgb to fall. You do not want to Riba reduce.
I was wondering why can't you start out doing the three drugs at regular dose and see if you und by week 4 and if your not you can do the DD then?
Telaprevir is a hard drug and if you do if with DD your really going to be messed up, and laid down. In the trial they automatically do blood work every two weeks while on Telaprevir.
I was wondering why can't you start out doing the three drugs at regular dose and see if you und by week 4 and if your not you can do the DD then?
Telaprevir is a hard drug and if you do if with DD your really going to be messed up, and laid down. In the trial they automatically do blood work every two weeks while on Telaprevir.
I'm rooting for you Magnum! Also, I don't see anything wrong with the plan. I did 1600mg of the Riba a day on one of my treatments. It was hard, but I survived it. I did need Procrit though. But, I didn't have any kidney damage. Incidentally, Telaprevir does need the Riba in order to work. Without it, it's absolutely useless. I know this from personal experience! Take care.
Susan400
Susan400
yes, that last part was my concern exactly, and now that you've explained stage and what happened last time I would think the concern well founded.
I would tend to agreed with the doc that longer tx, especially with a formerly resistant strain may make the most sense, but at regular not excessive doses.
In fact, I think it's going to be incumbant upon you, as it was on me, to make sure of your other drug interactions as well...as per all the discussions on my P450 threads...
the realization has to be this is your last chance probably to treat, and you need to be proactive and keep on top of how the liver is handling it...otherwise this could push you right up the MELD Chart.
So, this doc knows why high dosing did to you last time? Which begs the question of why he is so sure it will work this time and not hasten your liver failure?
HAs something distinct changed in your med profile? Like for instance are you not on the same BP meds or something.....there are so many meds that complicate the livers response to tx its just hard to believe he would suggest double dosing given your history unless you had dropped a lot of weight and gotten off of some other toxic meds, or something.
BTW...and you probably know this, but a recent study sited interferon as only 15% of the equation in treatment working. Don't know how accurate that is, but it's probably close, since almost no-one cleared with INF as a mono therapy....anyway, since it is the smaller of the components, the sense of DDing the INF makes even less sense given it's down sides. The higher Riba on the other hand (in Karen Lindahl;s study had everyone SVRing...but a 20% kidney failure. Somewhere in the SOC range lies sanity.
I don't envy you trying to ferret out what to do here....the trouble is, we are all deparate by stage 4 (me too) and what that does is make us more vunerable and open to any and all suggestions....the issue though, is also not to become statistics for what doesn't work in the process. I've signed onto guinea pig status in several areanas Re this disease, but then I watch my labs like a hawk because the proverbial straw on the camels back is a daily concern.
The alinia has not budged my labs in any regard....my tramadol doubled my ALT and so on...so you need a complete analysis of what else you must take weighed into the equation as well.
Good that you are willing to question...and get the rescue drugs answered for certain.
Remember most docs treating this disease have no clue what the side effects are like, not from a personal "physical encounters of the worst kind" point of view....and so their ability to think macochistically often far exceeds where any former patient might go with it.
mb
I would tend to agreed with the doc that longer tx, especially with a formerly resistant strain may make the most sense, but at regular not excessive doses.
In fact, I think it's going to be incumbant upon you, as it was on me, to make sure of your other drug interactions as well...as per all the discussions on my P450 threads...
the realization has to be this is your last chance probably to treat, and you need to be proactive and keep on top of how the liver is handling it...otherwise this could push you right up the MELD Chart.
So, this doc knows why high dosing did to you last time? Which begs the question of why he is so sure it will work this time and not hasten your liver failure?
HAs something distinct changed in your med profile? Like for instance are you not on the same BP meds or something.....there are so many meds that complicate the livers response to tx its just hard to believe he would suggest double dosing given your history unless you had dropped a lot of weight and gotten off of some other toxic meds, or something.
BTW...and you probably know this, but a recent study sited interferon as only 15% of the equation in treatment working. Don't know how accurate that is, but it's probably close, since almost no-one cleared with INF as a mono therapy....anyway, since it is the smaller of the components, the sense of DDing the INF makes even less sense given it's down sides. The higher Riba on the other hand (in Karen Lindahl;s study had everyone SVRing...but a 20% kidney failure. Somewhere in the SOC range lies sanity.
I don't envy you trying to ferret out what to do here....the trouble is, we are all deparate by stage 4 (me too) and what that does is make us more vunerable and open to any and all suggestions....the issue though, is also not to become statistics for what doesn't work in the process. I've signed onto guinea pig status in several areanas Re this disease, but then I watch my labs like a hawk because the proverbial straw on the camels back is a daily concern.
The alinia has not budged my labs in any regard....my tramadol doubled my ALT and so on...so you need a complete analysis of what else you must take weighed into the equation as well.
Good that you are willing to question...and get the rescue drugs answered for certain.
Remember most docs treating this disease have no clue what the side effects are like, not from a personal "physical encounters of the worst kind" point of view....and so their ability to think macochistically often far exceeds where any former patient might go with it.
mb
I was tested twice for IR, and I'm okay. The first test alarmed Dr. Gish, but we found out that the lame “professional” doctor’s assistant did NOT write "Fasting" on the lab request. The second time she did and it was normal. So much for professionals you trust your life to....
I have to agree with you to a certain extend about beating the horse until he can't neigh anymore. I did drop from 3,200,000 to 6,500 on my last (4th) treatment with over-dosing of Infergen. It was working, but it was a race as to who would be dead first, the virus or me. The way it appeared on the blood work, the swelling of the liver, the ALT and AST in the 700's, the Bilirubin through the roof, it would have been me.
And so we go on and on. I’ve often wondered what would have happened if I would not have treated four times at all and instead waited for something like Telaprivir. I’m sure my body would be in better shape now. I used to model. Not anymore......
Magnum
I have to agree with you to a certain extend about beating the horse until he can't neigh anymore. I did drop from 3,200,000 to 6,500 on my last (4th) treatment with over-dosing of Infergen. It was working, but it was a race as to who would be dead first, the virus or me. The way it appeared on the blood work, the swelling of the liver, the ALT and AST in the 700's, the Bilirubin through the roof, it would have been me.
And so we go on and on. I’ve often wondered what would have happened if I would not have treated four times at all and instead waited for something like Telaprivir. I’m sure my body would be in better shape now. I used to model. Not anymore......
Magnum
I don't get it, either. Why go with the same old-same old, when you've got the new and improved?
His train of thought is that if and when we bring the viral count down enough, then we introduce the protease inhibitor.
So, if the viral count doesn't go down enough, you don't even try the TV?
His train of thought is that if and when we bring the viral count down enough, then we introduce the protease inhibitor.
So, if the viral count doesn't go down enough, you don't even try the TV?
IMHO he is on the right path but I would ask him to consider an even more aggressive start. I don't know if he can work up an approximation or what category you fall into but if he does some legwork using your past responses it may provide a clue as to what he needs to do. I KNOW you are cirrhotic and that means a reduced chance of success. It may also mean more sensitivity to the drugs. Do you think that you can decide what group you best fit into: null responder, non responder, breakthrough or relapser? I would guess that if you were a past relapser or experienced a viral breakthrough you chances could be quite good. IF you fall into the other categories you may need to dig a little harder to experience success.
The idea of pre-dosing is good but it may not be enough from your description. If your doctor would look at the latest Boceprevir trial data from EASl he would see that both 24 and 48 week treatment arms did about 10% better when a 4 week SOC lead in was used. I would venture a guess that using that same tool with Telaprevir will boost the SVR rate 10% as well. I would not cheap out and try to get by with less. This has been proven to work. It also allows you to see if you will be able to tolerate TX. I also like the idea of a surge right before or during the first week or two of TVR and dose according to your response but by adding the TVR it just may become too too much to sustain for long
If they were to look at EASL they will also see a great article on IV milk thistle that can be used to bring down viral load. This was used effectively after people rebounded I believe. It was used as a "rescue" and it was able to bring some of the patients to clear again. IF this were to work I guess I wonder if it could be used to lower your viral load before predosing and possibly up to the introduction of Telaprevir.
If they look to EASL 2009 They will also see an interesting article on SAM-e that produced higher SVR rates when used with SOC. This might be used all during TX.
There were 2 presentations on Alinia showing that it too was effective in producing higher SVR's. You might consider pre-dosing with alinia but it is possible that it could become too much to also treat with it and TVR and SOC. Still it may help you get that early response that you need to get clear.
These are a few ideas. I know that they may be overkill and I am not suggesting using them all but in some ways they could nestle together without too many interactions. I want to take this time to mention what you already know; since there are inherent resistance issues with PI's you need to clear and SVR on this treatment since retreating with PI's a second time may have less chance of working.
Look at the boceprevir response tables and see that people who treated 48 weeks did better than 24 weeks. It probably makes sense for a person with a meld score to do the longer term TX.
By the way; I hope he also has some "Plan B" worked out and that suggests the possible use of rescue drugs
OK; food for thought and if links are needed I may be able to send them; maybe on a different post.
Best,
Willy
The idea of pre-dosing is good but it may not be enough from your description. If your doctor would look at the latest Boceprevir trial data from EASl he would see that both 24 and 48 week treatment arms did about 10% better when a 4 week SOC lead in was used. I would venture a guess that using that same tool with Telaprevir will boost the SVR rate 10% as well. I would not cheap out and try to get by with less. This has been proven to work. It also allows you to see if you will be able to tolerate TX. I also like the idea of a surge right before or during the first week or two of TVR and dose according to your response but by adding the TVR it just may become too too much to sustain for long
If they were to look at EASL they will also see a great article on IV milk thistle that can be used to bring down viral load. This was used effectively after people rebounded I believe. It was used as a "rescue" and it was able to bring some of the patients to clear again. IF this were to work I guess I wonder if it could be used to lower your viral load before predosing and possibly up to the introduction of Telaprevir.
If they look to EASL 2009 They will also see an interesting article on SAM-e that produced higher SVR rates when used with SOC. This might be used all during TX.
There were 2 presentations on Alinia showing that it too was effective in producing higher SVR's. You might consider pre-dosing with alinia but it is possible that it could become too much to also treat with it and TVR and SOC. Still it may help you get that early response that you need to get clear.
These are a few ideas. I know that they may be overkill and I am not suggesting using them all but in some ways they could nestle together without too many interactions. I want to take this time to mention what you already know; since there are inherent resistance issues with PI's you need to clear and SVR on this treatment since retreating with PI's a second time may have less chance of working.
Look at the boceprevir response tables and see that people who treated 48 weeks did better than 24 weeks. It probably makes sense for a person with a meld score to do the longer term TX.
By the way; I hope he also has some "Plan B" worked out and that suggests the possible use of rescue drugs
OK; food for thought and if links are needed I may be able to send them; maybe on a different post.
Best,
Willy
Point well taken. I will present your impression of the treatment to him. I also plan to definitely ask more questions, as I was nearly killed with the over-dosing of Infergen. We are entering uncharted waters with the new protease inhibitors. While everything seems wonderful as far as results so far in clinical trials, there remains the long term effects. At first I criticized the FDA for having us wait so long for the release, but in hindsight, it's no good to eventually receive the drug if in three years, you die from it.
Oh, the injustice of it all, spending $9,000,000,000 per month on a useless war when we could use even .05% of that to expand the research and fund more laboratories to eradicate this dreadful disease. Fear may overtake most of us, but as my father died in 1982 from Hepatitis C, I'm thankful I have a chance with new treatments. He had no chance at all at that time.
I'm sure most of us agree there's not enough publicity or visible anger shown on the nightly news towards the government's lack of funding a good chunk of money to help us, but the media is quick to state the Octomom is going to get a tattoo. The world must be laughing at us.
I say write to your congressman, your constituents, your state legislators, your governor, and yes, your leader (wherever you may be), and at least vent your frustration at the slow and limited research pace and fast human damage of this insidious disease.
Magnum
Oh, the injustice of it all, spending $9,000,000,000 per month on a useless war when we could use even .05% of that to expand the research and fund more laboratories to eradicate this dreadful disease. Fear may overtake most of us, but as my father died in 1982 from Hepatitis C, I'm thankful I have a chance with new treatments. He had no chance at all at that time.
I'm sure most of us agree there's not enough publicity or visible anger shown on the nightly news towards the government's lack of funding a good chunk of money to help us, but the media is quick to state the Octomom is going to get a tattoo. The world must be laughing at us.
I say write to your congressman, your constituents, your state legislators, your governor, and yes, your leader (wherever you may be), and at least vent your frustration at the slow and limited research pace and fast human damage of this insidious disease.
Magnum
gee can't stop spinning here...you know that when folks get the teleprevir they see significant drops very quickly right? I mean even those who have treated multiple times before unsuccesssfully see these drops.
So my final question is, why beat a dead horse? I mean you have tried unsuccessfully with the SOC drugs 4 times, and they haven't gotten you there 4 times...so doubling up on them is like dragging the dead horse home after beating it...so you can beat it some more the next day...why would something that didn't work ever now be able to?
I mean, if these drugs have never worked alone for you, why make them the stars at the party? I would think 4th time treating that doing things differently would make more sense, and especially if you could protect the liver by a slight regime adjustment such as the Alinia addition, which has stats similar to DDing as to VL reduction pre-tx.
Also, have you looked at any of the threads in this forum on Insulin Resistance or discovered whether you have any IR. If this were the case, doing something to get your IR under control would be more condusive to your eventual SVR than DDing, again with far less risk involved.
mb
So my final question is, why beat a dead horse? I mean you have tried unsuccessfully with the SOC drugs 4 times, and they haven't gotten you there 4 times...so doubling up on them is like dragging the dead horse home after beating it...so you can beat it some more the next day...why would something that didn't work ever now be able to?
I mean, if these drugs have never worked alone for you, why make them the stars at the party? I would think 4th time treating that doing things differently would make more sense, and especially if you could protect the liver by a slight regime adjustment such as the Alinia addition, which has stats similar to DDing as to VL reduction pre-tx.
Also, have you looked at any of the threads in this forum on Insulin Resistance or discovered whether you have any IR. If this were the case, doing something to get your IR under control would be more condusive to your eventual SVR than DDing, again with far less risk involved.
mb
I forgot to mention, he also plans on 48 weeks total even if I clear. Why? Because his experience shows some people even with the VX-950 clearance, have relapsed. So why go through all this to possibly relapse? He thinks not. Who knows, by late 2010, there could be something even more powerful than VX-950 and for treating a relapse situation as well. He also mentioned that it will be at least six years before there’s a treatment without Interferon and the nasty Ribavirin. Can you wait?
To his3707
As to your question of how do you go about getting the "compassionate use" of Telaprivir before its release? Aside from begging, you have your doctor fill and present a series of documents to the FDA and eventually Vertex. Search my archives on this and it will tell you everything, including where you can download the documents, etc...
I might add that the Gastro feels that a letter written by Hepatologist Dr. Gish (Director of Liver Transplants for the West Coast) regarding my need now of VX-950, will pull some weight.
There is a caveat with Vertex though. They may very well stick to their guns and not release for “compassionate use” for the simple reason of liability. Imagine if you did this drug and died from it before the clinical trials were over? Perish the thought of arguing with them if they flatly say “no”. But, without asking, you get nothing.
In other words, it's no guarantee and it is a long road, but as Descartes wrote... Without a dream, there's nothing to reach for"...
Magnum
To his3707
As to your question of how do you go about getting the "compassionate use" of Telaprivir before its release? Aside from begging, you have your doctor fill and present a series of documents to the FDA and eventually Vertex. Search my archives on this and it will tell you everything, including where you can download the documents, etc...
I might add that the Gastro feels that a letter written by Hepatologist Dr. Gish (Director of Liver Transplants for the West Coast) regarding my need now of VX-950, will pull some weight.
There is a caveat with Vertex though. They may very well stick to their guns and not release for “compassionate use” for the simple reason of liability. Imagine if you did this drug and died from it before the clinical trials were over? Perish the thought of arguing with them if they flatly say “no”. But, without asking, you get nothing.
In other words, it's no guarantee and it is a long road, but as Descartes wrote... Without a dream, there's nothing to reach for"...
Magnum
well I'm totally rooting for you to get this compassionate use...
although I wish you could share your doctors reasoning with us. I know you said he though about it a lot...but I'm concerned for several reasons.
1. We know the teleprevir works better than the riba, so the only advantage to preloading anything is to get to UND quicker and have a better outcome especially if the length of teleprevir is to be limited to 6 month tx this might make sense.
2. However, you still are treating for the 4th time, and I have no idea at what stage/grade
My question to your doc is how likely is this to overload your liver. We know that the higher the Riba the more the chance of kidney fibrosis and or failure, and doubling INF is dangerous as well as brutal at any stage but especially in later stages. It seems a lot of doctors are doing this now, or else desparate patients are doing it on their own, but it would make more sense to me if you were say to preload with some alinia, and not OD the Riba, nor rather than to double your INF...as this can also lower VL significantly but with no where remotely close to the deliterious side effects.
3. Is the doc trying to make sure you succeed even if it costs you your liver or kidneys?
I only ask this because I ALSO wanted very much to double my meds until I tried briefly, and also read that 1 in 5 with Higher Riba dosing lost a kidney...between that and the DD of INF over one week...it cured me. Of course, it's your body, and you may react differently....but most of the people who have DD'd have later said they wish they hadn't...at least from what I've read.
4. I think that DD should require a weekly CBC etc. It takes time for neupo or epo to work...and the sooner you catch a tank the better...plus, you are likely to tank before you even get to the Vertex drug...how does that effect tx when the telprevir is hardest on the WBC of anything....I'm just saying...this might be a genius reasoning, or something that will blow up in your liver, not his...so I would want him to define his reasoning and see the studies where predosing did make a distinct difference.
5. Also, Vertex may have some guidelines even for compassionate use, just as they would for SOC...those guidelines might include being removed from tx should platelets fall below acceptable levels. I'd want to know what those guidelines were up front, and be careful not to tank myself in the first month of PI tx if it were me.
Hoping not to discourage you here magnum, just wanting to make sure you and your doc have thouroughly discussed all this and that he is aware of the inherent risks as you should also be.
6. Also the final thought that comes to mind is that "compassion use" may mean that your insurance company may look at the whole tx as off label...in which case how likely are you to get rescue drugs such as epo/neupo. I'd want this answered as well.
7. My prayers are with you, that you get the permission, and also that God grant your doctor superior wisdom and a real concern for you as his patient.
mb
although I wish you could share your doctors reasoning with us. I know you said he though about it a lot...but I'm concerned for several reasons.
1. We know the teleprevir works better than the riba, so the only advantage to preloading anything is to get to UND quicker and have a better outcome especially if the length of teleprevir is to be limited to 6 month tx this might make sense.
2. However, you still are treating for the 4th time, and I have no idea at what stage/grade
My question to your doc is how likely is this to overload your liver. We know that the higher the Riba the more the chance of kidney fibrosis and or failure, and doubling INF is dangerous as well as brutal at any stage but especially in later stages. It seems a lot of doctors are doing this now, or else desparate patients are doing it on their own, but it would make more sense to me if you were say to preload with some alinia, and not OD the Riba, nor rather than to double your INF...as this can also lower VL significantly but with no where remotely close to the deliterious side effects.
3. Is the doc trying to make sure you succeed even if it costs you your liver or kidneys?
I only ask this because I ALSO wanted very much to double my meds until I tried briefly, and also read that 1 in 5 with Higher Riba dosing lost a kidney...between that and the DD of INF over one week...it cured me. Of course, it's your body, and you may react differently....but most of the people who have DD'd have later said they wish they hadn't...at least from what I've read.
4. I think that DD should require a weekly CBC etc. It takes time for neupo or epo to work...and the sooner you catch a tank the better...plus, you are likely to tank before you even get to the Vertex drug...how does that effect tx when the telprevir is hardest on the WBC of anything....I'm just saying...this might be a genius reasoning, or something that will blow up in your liver, not his...so I would want him to define his reasoning and see the studies where predosing did make a distinct difference.
5. Also, Vertex may have some guidelines even for compassionate use, just as they would for SOC...those guidelines might include being removed from tx should platelets fall below acceptable levels. I'd want to know what those guidelines were up front, and be careful not to tank myself in the first month of PI tx if it were me.
Hoping not to discourage you here magnum, just wanting to make sure you and your doc have thouroughly discussed all this and that he is aware of the inherent risks as you should also be.
6. Also the final thought that comes to mind is that "compassion use" may mean that your insurance company may look at the whole tx as off label...in which case how likely are you to get rescue drugs such as epo/neupo. I'd want this answered as well.
7. My prayers are with you, that you get the permission, and also that God grant your doctor superior wisdom and a real concern for you as his patient.
mb
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