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Please check out the slide set by Dr. Mitchell Shiffman released today at Clinical Care Options.
clinicaloptions.com
clinicaloptions.com
Since you seem to be following my posts on Lindahl, you probably know that the first thing I would personally do if treating right now would be to contact Lindahl to see if more data has been developed other than the 10 from the small pilot study.
That said, and while I still see VHDR (very high dose ribavirin) as some benefit in a very select group -- I'm pretty sure that if I were treating today, I'd be more interested in the PI trials rather than VHDR, because of toxicity issues both with riba and Peg with VHDR.
No doubt, this (toxicity) is one reason VHDR has not been pursued in this country very much, i.e. the major researchers have been busy with the PI trials which they feel is a better, less toxic approach.
Keep in mind that one of the problems with SOC is toxicity and QOL during tx. In concept the PI's deal with both, VHDR makes both worse.
On the other hand VHPLC testing can still nevertheless be useful within SOC to make sure "optimum" riba levels are being maintained. And I use quote marks around optimum because I'm now using it in the sense of optimum for SOC and not "optimum" as used in the VHDR studies. Problem is, I don't think there is much data on what optimum serum riba levels are for SOC, so that would have to be developed/researched more.
-- Jim
That said, and while I still see VHDR (very high dose ribavirin) as some benefit in a very select group -- I'm pretty sure that if I were treating today, I'd be more interested in the PI trials rather than VHDR, because of toxicity issues both with riba and Peg with VHDR.
No doubt, this (toxicity) is one reason VHDR has not been pursued in this country very much, i.e. the major researchers have been busy with the PI trials which they feel is a better, less toxic approach.
Keep in mind that one of the problems with SOC is toxicity and QOL during tx. In concept the PI's deal with both, VHDR makes both worse.
On the other hand VHPLC testing can still nevertheless be useful within SOC to make sure "optimum" riba levels are being maintained. And I use quote marks around optimum because I'm now using it in the sense of optimum for SOC and not "optimum" as used in the VHDR studies. Problem is, I don't think there is much data on what optimum serum riba levels are for SOC, so that would have to be developed/researched more.
-- Jim
Here is an exerpt from some commentary on the Lindahl VHDR study that deals with the toxicity issues of VHDR per the Lindahl study. It therefore seems to me that anyone thinking about VHDR versus a PI trial, for example, should have some very well thought reasons for such an undertaking. I know I did in '05 when I thought I could handle VHDR, but in '05 I didn't know what a PI or Telaprevir was. As discussed before, my little experiment with VHDR failed for a number of reasons, but in the end I barely was able to tolerate the 1200 mg/day of ribavirin from SOC.
"... The results of this study are indeed striking but a note of caution must be struck. Foremost is the issue of safety. One of the major limitations to combination therapy is the high frequency of side effects, some of which may be serious and life-threatening. In the two large multicenter registration trials, 10% to 14% of patients required discontinuation of therapy and 32% to 42% required dose modification for serious or severe side effects.[1][2] Higher doses of ribavirin would undoubtedly lead to more side effects. Hemolytic anemia is the major risk associated with ribavirin, and, if defined as a hemoglobin level less than 10g/ dL, occurred in 7 of 10 patients. All patients required hemopoetic growth factor, two required blood transfusion and four required dose reduction or temporary discontinuation of the drug to manage side effects. Furthermore, all patients experienced a reduction in ability to work, although, quality-of-life was not specifically assessed. The need for erythropoietin, blood transfusion, and loss of work are not trivial matters particularly in the typical patient with hepatitis C who has few if any symptoms and is largely fully functional. Anemia caused by ribavirin can induce cardiovascular and cerebrovascular incidents in susceptible patients. Thus, even with intensive monitoring this high-dose ribavirin regimen can be life-threatening..."
http://www.hepcnet.net/boards/medsforum/index.cgi?noframes;read=1412
"... The results of this study are indeed striking but a note of caution must be struck. Foremost is the issue of safety. One of the major limitations to combination therapy is the high frequency of side effects, some of which may be serious and life-threatening. In the two large multicenter registration trials, 10% to 14% of patients required discontinuation of therapy and 32% to 42% required dose modification for serious or severe side effects.[1][2] Higher doses of ribavirin would undoubtedly lead to more side effects. Hemolytic anemia is the major risk associated with ribavirin, and, if defined as a hemoglobin level less than 10g/ dL, occurred in 7 of 10 patients. All patients required hemopoetic growth factor, two required blood transfusion and four required dose reduction or temporary discontinuation of the drug to manage side effects. Furthermore, all patients experienced a reduction in ability to work, although, quality-of-life was not specifically assessed. The need for erythropoietin, blood transfusion, and loss of work are not trivial matters particularly in the typical patient with hepatitis C who has few if any symptoms and is largely fully functional. Anemia caused by ribavirin can induce cardiovascular and cerebrovascular incidents in susceptible patients. Thus, even with intensive monitoring this high-dose ribavirin regimen can be life-threatening..."
http://www.hepcnet.net/boards/medsforum/index.cgi?noframes;read=1412
Here is an exerpt from some commentary on the Lindahl VHDR study that deals with the toxicity issues of VHDR per the Lindahl study. It therefore seems to me that anyone thinking about VHDR versus a PI trial, for example, should have some very well thought reasons for such an undertaking. I know I did in '05 when I thought I could handle VHDR, but in '05 I didn't know what a PI or Telaprevir was. As discussed before, my little experiment with VHDR failed for a number of reasons, but in the end I barely was able to tolerate the 1200 mg/day of ribavirin from SOC.
"... The results of this study are indeed striking but a note of caution must be struck. Foremost is the issue of safety. One of the major limitations to combination therapy is the high frequency of side effects, some of which may be serious and life-threatening. In the two large multicenter registration trials, 10% to 14% of patients required discontinuation of therapy and 32% to 42% required dose modification for serious or severe side effects.[1][2] Higher doses of ribavirin would undoubtedly lead to more side effects. Hemolytic anemia is the major risk associated with ribavirin, and, if defined as a hemoglobin level less than 10g/ dL, occurred in 7 of 10 patients. All patients required hemopoetic growth factor, two required blood transfusion and four required dose reduction or temporary discontinuation of the drug to manage side effects. Furthermore, all patients experienced a reduction in ability to work, although, quality-of-life was not specifically assessed. The need for erythropoietin, blood transfusion, and loss of work are not trivial matters particularly in the typical patient with hepatitis C who has few if any symptoms and is largely fully functional. Anemia caused by ribavirin can induce cardiovascular and cerebrovascular incidents in susceptible patients. Thus, even with intensive monitoring this high-dose ribavirin regimen can be life-threatening..."
http://www.hepcnet.net/boards/medsforum/index.cgi?noframes;read=1412
"... The results of this study are indeed striking but a note of caution must be struck. Foremost is the issue of safety. One of the major limitations to combination therapy is the high frequency of side effects, some of which may be serious and life-threatening. In the two large multicenter registration trials, 10% to 14% of patients required discontinuation of therapy and 32% to 42% required dose modification for serious or severe side effects.[1][2] Higher doses of ribavirin would undoubtedly lead to more side effects. Hemolytic anemia is the major risk associated with ribavirin, and, if defined as a hemoglobin level less than 10g/ dL, occurred in 7 of 10 patients. All patients required hemopoetic growth factor, two required blood transfusion and four required dose reduction or temporary discontinuation of the drug to manage side effects. Furthermore, all patients experienced a reduction in ability to work, although, quality-of-life was not specifically assessed. The need for erythropoietin, blood transfusion, and loss of work are not trivial matters particularly in the typical patient with hepatitis C who has few if any symptoms and is largely fully functional. Anemia caused by ribavirin can induce cardiovascular and cerebrovascular incidents in susceptible patients. Thus, even with intensive monitoring this high-dose ribavirin regimen can be life-threatening..."
http://www.hepcnet.net/boards/medsforum/index.cgi?noframes;read=1412
Last paragraph, two posts back, should read in part:
On the other hand HPLC (high performance liquid chromatography) testing for serum riba levels can still nevertheless be useful within SOC to make sure "optimum" riba levels are being maintained.
On the other hand HPLC (high performance liquid chromatography) testing for serum riba levels can still nevertheless be useful within SOC to make sure "optimum" riba levels are being maintained.
on the one hand, the overdosing doesn't make much sense based on those stats does it,
I'm confused as to how she got to a 90% cure with such a drop out.dose reduction rate.
Not knowing how the numbers are skewed, I can only assume that number is based on only those who finished tx. No other way to get there. You can't take that drop out rate and dose reduction group, and still reach 90% any other way except to exclude them from the final numbers.
Which makes the whole doubling up thing pretty scary in my mind. Many won't continue, many will be transfused....
Not that a procrit or a transfusion doesn't appeal over 4th stage liver disease....
but then you have the Alagirl's of our world proving one thing continually can lead to another, and another...
On the other hand Teleprevir is causing worse sides in some ways isn't it?
I mean....
How do we know the teleprevir isn't just a stronger Ribaesque molecule that creates all the same issues, and then some......while it achieves a faster cure maybe....OK....but faster at the patient's expense, and the only real winner may then be the insurances in this case. Getting there 6 months quicker and saving big bucks.
I think maybe if HR HR HR HR
HR could or would explain how these molecules, Ribavirin/teleprevir differ it would help many.
this is all pretty frustrating.
I'm confused as to how she got to a 90% cure with such a drop out.dose reduction rate.
Not knowing how the numbers are skewed, I can only assume that number is based on only those who finished tx. No other way to get there. You can't take that drop out rate and dose reduction group, and still reach 90% any other way except to exclude them from the final numbers.
Which makes the whole doubling up thing pretty scary in my mind. Many won't continue, many will be transfused....
Not that a procrit or a transfusion doesn't appeal over 4th stage liver disease....
but then you have the Alagirl's of our world proving one thing continually can lead to another, and another...
On the other hand Teleprevir is causing worse sides in some ways isn't it?
I mean....
How do we know the teleprevir isn't just a stronger Ribaesque molecule that creates all the same issues, and then some......while it achieves a faster cure maybe....OK....but faster at the patient's expense, and the only real winner may then be the insurances in this case. Getting there 6 months quicker and saving big bucks.
I think maybe if HR HR HR HR
HR could or would explain how these molecules, Ribavirin/teleprevir differ it would help many.
this is all pretty frustrating.
I think you have to take the study for what it is -- and yes, there were only ten participants (total) and only one drop out. You can find the details you want by ordering up a full-text version if so motivated. I have it on one of my hard disks but not able to supply a link.
As to Telaprevir, again, it is what it is. So far, it appears 60% SVR in 24 weeks, and that's without helper drugs. That's a better rate than SOC in less than half the treatment time which means half the exposure to the drugs, the biggie IMO being less exposure to interferon.
Telaprevir, certainly isn't the end all, just one example of perhaps a better alternative now, to for example very high dose ribavirin, for reasons previously cited.
Did you finally take your week 12 test? Any resuts? Last I remember you sitll had less than a one log drop at week 10. The time for higher dose (riba or otherwise) intervetion IMO would have been back around week 4, when you still had less than a one-log drop. At this point, especially if you don't have a dramatic drop at week 12, I think you seriously have to listen to your doctors and stop. Rest up. And then fight another day, with whatever appears to be the best approach at that time. And given you were given no heads-up at week 4 with such a weak response -- in fact, weren't you told things were "OK"? -- I think treating with a new set of doctors next time would be a reasonable decision.
-- Jim
As to Telaprevir, again, it is what it is. So far, it appears 60% SVR in 24 weeks, and that's without helper drugs. That's a better rate than SOC in less than half the treatment time which means half the exposure to the drugs, the biggie IMO being less exposure to interferon.
Telaprevir, certainly isn't the end all, just one example of perhaps a better alternative now, to for example very high dose ribavirin, for reasons previously cited.
Did you finally take your week 12 test? Any resuts? Last I remember you sitll had less than a one log drop at week 10. The time for higher dose (riba or otherwise) intervetion IMO would have been back around week 4, when you still had less than a one-log drop. At this point, especially if you don't have a dramatic drop at week 12, I think you seriously have to listen to your doctors and stop. Rest up. And then fight another day, with whatever appears to be the best approach at that time. And given you were given no heads-up at week 4 with such a weak response -- in fact, weren't you told things were "OK"? -- I think treating with a new set of doctors next time would be a reasonable decision.
-- Jim
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