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Using PI's in treating cirrhotics
There was a recent presentation in CCO regarding treating patients who are cirrhotic with PI's. Generally speaking, cirrhotics are excluded from trials. Therefore there is not enough information on their treatments.
http://www.clinicaloptions.com/inPractice/Hepatology/Hepatology/ch8_Mgmt_of_Hep_C_Infection/Pages/Page%207/Subpage%205a.aspx
This is the CUPIC trial and is being held in France. The trial has not yet been completed but they do have the week 16 results and UND is up about 20% over SOC for both Telaprevir and Boceprevir.
They discussed the treatment of anemia in cirrhotics. The presenter said that, although there were not significant numbers of cirrhotics in the original TEL and BOC trial data, the "trend" is that cirrhotics do not respond as well as noncirrhotics to dose reduction. Therefore, in the CUPID, there were only a small percent (13%) of the population who dose reduced. Most used EPO (45-50%) and transfusions. It will be interesting to see later when this trial has finished, how the SVR rates are for dose reducers and Epo users.
The presenters said the following are risk factors for reaching grade 3\4 anemia (<8g/dL within the first 16 weeks of treatment:
-Female
-over age 65
-baseline HGB <12 for women , <13 for men
-No lead in
He also discussed the rsik factors for hepatic decompensation
- low platelets <100
-borderline or low albumin 10
It will be interseting to see how this trial pans out. The presenters also said that there are more trials for cirrhotics beginning now in the states.
http://www.clinicaloptions.com/inPractice/Hepatology/Hepatology/ch8_Mgmt_of_Hep_C_Infection/Pages/Page%207/Subpage%205a.aspx
This is the CUPIC trial and is being held in France. The trial has not yet been completed but they do have the week 16 results and UND is up about 20% over SOC for both Telaprevir and Boceprevir.
They discussed the treatment of anemia in cirrhotics. The presenter said that, although there were not significant numbers of cirrhotics in the original TEL and BOC trial data, the "trend" is that cirrhotics do not respond as well as noncirrhotics to dose reduction. Therefore, in the CUPID, there were only a small percent (13%) of the population who dose reduced. Most used EPO (45-50%) and transfusions. It will be interesting to see later when this trial has finished, how the SVR rates are for dose reducers and Epo users.
The presenters said the following are risk factors for reaching grade 3\4 anemia (<8g/dL within the first 16 weeks of treatment:
-Female
-over age 65
-baseline HGB <12 for women , <13 for men
-No lead in
He also discussed the rsik factors for hepatic decompensation
- low platelets <100
-borderline or low albumin 10
It will be interseting to see how this trial pans out. The presenters also said that there are more trials for cirrhotics beginning now in the states.
OH BOY - correction in the at risk for decompensation --
albumin levels <35 -- not 10! sorry about that. I don't know much about albumin levels but they said this was a borderline number.
bo girl -- yes, those are all pre-treatment levels given -- the <35 albumin and the <100 platelets
"Hepatic Decompensation means liver failure so I'm thinking it means during (or as a result of) treatment. "
Yes, this does mean decompensation as a result of treatment. This is what happened to our member ejoili. She is a long way from having a MELD score high enough to TP but nonetheless, she has decomped.
Another typo - I should not be allowed at a computer/typewriter late at night. ... among the risk factors for decomp, a MELD FACTOR OVER 10, NOT UNDER! geesch!
Thanks for writing that all out, Hector. (I was trying my best to understand Bourliere's English and writing notes while watching the video). You hit on some other points such as there were more serious infections among the cirrhotics in the CUPID. (My doctor was a lot firmer about the use of neupogen during my treatment, since cirrhotics have more of a risk with infection.)
Still, they did say in this interview with Bourliere that none of the findings were unexpected. No, they are not great (higher anemia, more deaths, more serious infection, greater overall adverse eventss) but these findings should not prevent doctors from treating cirrhotics.
albumin levels <35 -- not 10! sorry about that. I don't know much about albumin levels but they said this was a borderline number.
bo girl -- yes, those are all pre-treatment levels given -- the <35 albumin and the <100 platelets
"Hepatic Decompensation means liver failure so I'm thinking it means during (or as a result of) treatment. "
Yes, this does mean decompensation as a result of treatment. This is what happened to our member ejoili. She is a long way from having a MELD score high enough to TP but nonetheless, she has decomped.
Another typo - I should not be allowed at a computer/typewriter late at night. ... among the risk factors for decomp, a MELD FACTOR OVER 10, NOT UNDER! geesch!
Thanks for writing that all out, Hector. (I was trying my best to understand Bourliere's English and writing notes while watching the video). You hit on some other points such as there were more serious infections among the cirrhotics in the CUPID. (My doctor was a lot firmer about the use of neupogen during my treatment, since cirrhotics have more of a risk with infection.)
Still, they did say in this interview with Bourliere that none of the findings were unexpected. No, they are not great (higher anemia, more deaths, more serious infection, greater overall adverse eventss) but these findings should not prevent doctors from treating cirrhotics.
Interim analysis of Compassionate Use of Protease Inhibitors in Viral C Cirrhosis (CUPIC)
Trial candidates:
'previous relapsers and partial responders to peginterferon/ribavirin with compensated Child-Pugh A cirrhosis and genotype 1 HCV infection.'
Summary of Key Conclusions
• In real-world setting, poor safety profiles for telaprevir- and boceprevir-based regimens in patients with genotype 1 HCV and compensated cirrhosis who had relapse or partial response to previous peginterferon (pegIFN)/ribavirin (RBV) therapy
• Rates of serious adverse events markedly higher (38% to 49%) than in phase III trial results (9% to 14%)[2-6]
• High rates of discontinuation because of adverse events (7% to 15%)
• Grade 3/4 anemia common with both regimens and responded poorly to erythropoietin
• High rates of undetectable HCV RNA through 16 weeks of therapy with both telaprevir- and boceprevir-based regimens
• SVR results awaited
• Preliminary results underscore need for careful monitoring of cirrhotic patients treated with telaprevir- or boceprevir-based regimens
Main Findings
• Both telaprevir- and boceprevir-based regimens associated with high rates of serious adverse events
• 6 deaths in telaprevir group from sepsis (n = 2), pneumopathy (n = 1), bleeding of esophageal varices (n = 1), encephalopathy (n = 1), and lung carcinoma (n = 1)
• 2 deaths in boceprevir group from bronchopulmonary infection (n = 1) and sepsis (n = 1)
• Most common grade 3/4 adverse events
• Telaprevir-based therapy: thrombocytopenia, anemia, infection, and rash
• Boceprevir-based therapy: anemia, thrombocytopenia, and asthenia
Premature treatment discontinuation by week 16
• Telaprevir - 26.0%
• Boceprevir - 23.9%
In this interim analysis, serious adverse event rates requiring admission to the hospital were high at 45% among telaprevir-treated patients and 33% in boceprevir-treated patients.
Decompensation:
'2.0% to 2.9% of patients treated with either protease inhibitor experienced hepatic decompensation.'
Anemia:
'Despite a high rate of erythropoietin use (46.3% to 53.8%), blood transfusions were required in 16.1% of telaprevir-treated patients and 6.3% of patients treated with boceprevir.'
Predictors of servere complications:
'Multivariate analyses identified 2 predictors of severe complications: baseline platelet counts of ≤ 100,000/mm3 and baseline serum albumin level of < 35 g/L.'
Cheers
Hector
Trial candidates:
'previous relapsers and partial responders to peginterferon/ribavirin with compensated Child-Pugh A cirrhosis and genotype 1 HCV infection.'
Summary of Key Conclusions
• In real-world setting, poor safety profiles for telaprevir- and boceprevir-based regimens in patients with genotype 1 HCV and compensated cirrhosis who had relapse or partial response to previous peginterferon (pegIFN)/ribavirin (RBV) therapy
• Rates of serious adverse events markedly higher (38% to 49%) than in phase III trial results (9% to 14%)[2-6]
• High rates of discontinuation because of adverse events (7% to 15%)
• Grade 3/4 anemia common with both regimens and responded poorly to erythropoietin
• High rates of undetectable HCV RNA through 16 weeks of therapy with both telaprevir- and boceprevir-based regimens
• SVR results awaited
• Preliminary results underscore need for careful monitoring of cirrhotic patients treated with telaprevir- or boceprevir-based regimens
Main Findings
• Both telaprevir- and boceprevir-based regimens associated with high rates of serious adverse events
• 6 deaths in telaprevir group from sepsis (n = 2), pneumopathy (n = 1), bleeding of esophageal varices (n = 1), encephalopathy (n = 1), and lung carcinoma (n = 1)
• 2 deaths in boceprevir group from bronchopulmonary infection (n = 1) and sepsis (n = 1)
• Most common grade 3/4 adverse events
• Telaprevir-based therapy: thrombocytopenia, anemia, infection, and rash
• Boceprevir-based therapy: anemia, thrombocytopenia, and asthenia
Premature treatment discontinuation by week 16
• Telaprevir - 26.0%
• Boceprevir - 23.9%
In this interim analysis, serious adverse event rates requiring admission to the hospital were high at 45% among telaprevir-treated patients and 33% in boceprevir-treated patients.
Decompensation:
'2.0% to 2.9% of patients treated with either protease inhibitor experienced hepatic decompensation.'
Anemia:
'Despite a high rate of erythropoietin use (46.3% to 53.8%), blood transfusions were required in 16.1% of telaprevir-treated patients and 6.3% of patients treated with boceprevir.'
Predictors of servere complications:
'Multivariate analyses identified 2 predictors of severe complications: baseline platelet counts of ≤ 100,000/mm3 and baseline serum albumin level of < 35 g/L.'
Cheers
Hector
Hepatic Decompensation means liver failure so I'm thinking it means during (or as a result of) treatment.
These figures are astounding. It'll be interesting to compare these values as the study progresses.
http://www.medhelp.org/user_photos/show/346687?personal_page_id=1282072
These figures are astounding. It'll be interesting to compare these values as the study progresses.
http://www.medhelp.org/user_photos/show/346687?personal_page_id=1282072
"He also discussed the rsik factors for hepatic decompensation
- low platelets <100
-borderline or low albumin 10
Hi Bean, does the <100 platelets refer to platelet # pre-treatment?
- low platelets <100
-borderline or low albumin 10
Hi Bean, does the <100 platelets refer to platelet # pre-treatment?
So true. I'm glad they are looking carefully at the risk factors. I'm glad they took a chance with me. But remember, my gastro said NO and I had to go the the transplant center.
BTW - My tp doc is seeing good numbers for low cancer rates with cirrhotics who treated. I think he said out of a 300ish, he only had 2. You know how good I am with all the stat stuff. But he was quite happy with the results. Me too. xoxo Thanks for the link Bean! Karen:)
BTW - My tp doc is seeing good numbers for low cancer rates with cirrhotics who treated. I think he said out of a 300ish, he only had 2. You know how good I am with all the stat stuff. But he was quite happy with the results. Me too. xoxo Thanks for the link Bean! Karen:)
can-do
Unfortunately many treatment doctors do not take cirrhosis into consideration or don't know what they should do about it. In that CUPID presentation there were more deaths there was more hepatic decompensation , but the fact is that thre are a lot of doctors reluctant to treat cirrhotics at all, and this trial has shown doctors that there has not been anything "unexpected" in the trial. After all, the cirrhotics are those that need treatment the most
Unfortunately many treatment doctors do not take cirrhosis into consideration or don't know what they should do about it. In that CUPID presentation there were more deaths there was more hepatic decompensation , but the fact is that thre are a lot of doctors reluctant to treat cirrhotics at all, and this trial has shown doctors that there has not been anything "unexpected" in the trial. After all, the cirrhotics are those that need treatment the most
idyllic
I haven't listened to the slide presentation yet but I looked at the other link. One thing they said in the CUPID presentation was that the cirrhotics in the trials of BOC and TEL before they were approved were not a real life popluation. They were mostly all compensted and therefore the results of those tests on cirrhotics are misleading.
I haven't listened to the slide presentation yet but I looked at the other link. One thing they said in the CUPID presentation was that the cirrhotics in the trials of BOC and TEL before they were approved were not a real life popluation. They were mostly all compensted and therefore the results of those tests on cirrhotics are misleading.
Yes it will be interesting to see the final results. I have never been one to think one size fits all when it comes to treating and its quite clear during the presentation given by Marc Bourliere that he feels dose reducing with cirrhotics is not a good ideal............ Thanks Kat
Here's a (recent) retrospective analysis about managing anaemia with the PI Bocprevir for treatment naive & compensated cirrhosis. I am not sure I interpreted the data the way the authors intended since the last sentence in the second paragraph (to me) made me think I would not want to dose reduce in the first place.
_________________
Amongst patients with cirrhosis, SVR rates were statistically similar with ribavirin dose reduction and use of EPO, 57 and 64% respectively. This was also the case for non-cirrhotic patients, with SVR rates of 72 and 73% respectively.
However, people with cirrhosis were significantly more likely than non-cirrhotics to add a second anaemia management strategy (44 vs 26%). Adding a second management strategy improved the likelihood of SVR, from 52 to 71% for people with cirrhosis and from 70 to 80% for non-cirrhotics.
http://www.aidsmap.com/page/2550118/
Slide presentation
http://www.chronicliverdisease.org/disease_focus/ppts/ch/HCV_Highlights_from_AASLD2012.pdf
_________________
Amongst patients with cirrhosis, SVR rates were statistically similar with ribavirin dose reduction and use of EPO, 57 and 64% respectively. This was also the case for non-cirrhotic patients, with SVR rates of 72 and 73% respectively.
However, people with cirrhosis were significantly more likely than non-cirrhotics to add a second anaemia management strategy (44 vs 26%). Adding a second management strategy improved the likelihood of SVR, from 52 to 71% for people with cirrhosis and from 70 to 80% for non-cirrhotics.
http://www.aidsmap.com/page/2550118/
Slide presentation
http://www.chronicliverdisease.org/disease_focus/ppts/ch/HCV_Highlights_from_AASLD2012.pdf
Yes, I watched that presentation too and noticed the same points that you noticed. Especially of interest were the remarks about Riba dose reduction in cirrhotics. I too await the final conclusions from the CUPIC trial.
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