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Restarting Incivek Triple Therapy
Yes, it's true. After conversations with the pharmacists, 3 doctors and a lab scientist who can speak about off label stats, we have decided to restart from the beginning.
I'll send more info later about what transpired.
God just keeps on blessing us!
Kat
I'll send more info later about what transpired.
God just keeps on blessing us!
Kat
I'm happy for you and look forward to hearing about your tx AND your SVR. When I started Incivik, it was not recommended for stage 4 cirrhosis. A transplant center treated me as a last ditch effort.
NOW, the numbers are out and cirrhotics did overwhelmingly GREAT as far as SVR. Prove em wrong hunnyo!
xo Karen:)
NOW, the numbers are out and cirrhotics did overwhelmingly GREAT as far as SVR. Prove em wrong hunnyo!
xo Karen:)
Ceanothus,
The release date on that article is very old in terms of HEP C development. I'll try to keep you all up to date on my progress as soon as I restart.
thanks again and keep those prayers coming,,,,we/I still need them.
:)
The release date on that article is very old in terms of HEP C development. I'll try to keep you all up to date on my progress as soon as I restart.
thanks again and keep those prayers coming,,,,we/I still need them.
:)
I wish you the best
My knowledge in this is that if Incivek it is taken for such a long time (a month) and then stopped, it is not to be restarted
But I guess you have taken your decission and you will go ahead with it
What I am seeing here being even more important is how your doctor is going to manage your low platelets. You are taking now a product to help raise your platelets , is that going to be enough to have you going through the 12 weeks of Incivek?
My knowledge in this is that if Incivek it is taken for such a long time (a month) and then stopped, it is not to be restarted
But I guess you have taken your decission and you will go ahead with it
What I am seeing here being even more important is how your doctor is going to manage your low platelets. You are taking now a product to help raise your platelets , is that going to be enough to have you going through the 12 weeks of Incivek?
Wish you the best moving forward Kat. You are venturing into new territory here so we hope to see a positive outcome. Hope you continue to post updates and your cbc's behave this time.
Thanks for everyone's feedback, we have been talking to as many people (pharmacists, hepatologists, hemotologists, and a scientist) before taking this step. I am very excited.
I can assure you all of this was taken into consideration. I can't post much now, but later will give all of you the details.
I didn't say there were long term studies. But the instances they are seeing now, is very good.
"Have they done any lab work to verify that your virus is still "wild" and not mutated to a drug-resistant variety or are they planning to play it by ear and determine that by how your VL responds to restarting tx?"
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My understanding is that she treated for one month, then stopped due to to poor labs (Platelets 19). She was tested a month after stopping Tx and was UND. Therefore, she is UND so they would not be able to determine if she still has any virus and what type it is (if it is below the level of DET).
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My understanding is that she treated for one month, then stopped due to to poor labs (Platelets 19). She was tested a month after stopping Tx and was UND. Therefore, she is UND so they would not be able to determine if she still has any virus and what type it is (if it is below the level of DET).
Oops, I see now that the link takes you to the table of contents for a larger body of work. The pertinent section is titled:
"On Treatment Management: Futility Rules and Prevention of Resistance"
"On Treatment Management: Futility Rules and Prevention of Resistance"
The link I was referring to is at bout this at: http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/HCV%20New%20Agents/Module/Practical_Guide.aspx?lg=filedownload#page31
Just in case that link doesn't work properly I also tried to copy and paste the whole text below, with the most relevant info nearer to the end of the report, but unfortunately, the tables and figures can't seem to be pasted, and they hold much of the important info. In my own words, the study looked at how many patients who failed triple tx with Telaprevir still had drug-resistant virus variants at different periods of time after tx, looking as far out as slightly over 16 months after stopping. It shows a fairly steady decline, with essentials no mutant variations remaining at 17 months. I hope you can access the link itself.
Boceprevir and Telaprevir Stopping Rules
The case patient is a 45-year-old man who experienced treatment failure on peginterferon/ribavirin; his treatment was discontinued after 12 weeks because his HCV RNA had not decreased by 2 log10 IU/mL. He has chosen to undergo retreatment with boceprevir plus peginterferon/ribavirin. The patient is infected with genotype 1 HCV with a baseline HCV RNA level of 2.3 million IU/mL and biopsy-proven fibrosis (Ishak score: 5 of 6). He tolerates therapy well, and his HCV RNA levels are 1700 IU/mL at Week 8 and 800 IU/mL at Week 12. How should you manage this patient now at Week 12 of therapy?
Graham R. Foster, FRCP, PhD:
This patient’s medication unfortunately must be stopped at Week 12, based on the futility rules outlined for boceprevir in the US Food and Drug Administration–approved label.[4] The futility rules dictate that all therapy should be discontinued in patients whose HCV RNA levels are ≥ 100 IU/mL at treatment Week 12, as well as in those who have detectable HCV RNA at treatment Week 24 (Table 1).[1,4]
The futility rules are slightly different for patients who are receiving telaprevir plus peginterferon/ribavirin. According to the US telaprevir label, all therapy should be discontinued in patients whose HCV RNA level is > 1000 IU/mL at treatment Weeks 4 or 12, and peginterferon/ribavirin should be discontinued at Week 24 if HCV RNA is detectable (Table 1).[1,5] Thus, the case patient’s HCV RNA level of 800 IU/mL at Week 12 of therapy meets the stopping rules for boceprevir-based therapy but not for telaprevir-based therapy.
For both agents, the assays used for determining HCV RNA levels should have a lower limit of HCV RNA quantification of ≤ 25 IU/mL and a limit of HCV RNA detection of approximately 10-15 IU/mL.
Table 1. Telaprevir and Boceprevir Stopping Rules[1,4,5]
It is essential that these stopping rules be strictly observed to reduce the risk of expanding the pool of drug-resistant viral variants. In the absence of therapy, HCV exists as a heterogeneous mixture of viral variants in which the majority of the species are likely to be susceptible to direct-acting agents, because most naturally occurring drug-resistant variants have lower replicative capacity (are “less fit”) than wild-type virus. However, in patients with treatment failure on protease inhibitor–based triple therapy, drug-susceptible viruses have been largely eliminated, and drug-resistant variants with varying levels of replicative fitness predominate. Continuing therapy with a direct-acting agent in the presence of ongoing viral replication provides continued selective pressure on drug-resistant variants, promoting the selection of additional mutations that can increase their replicative fitness.
In phase III boceprevir trials, 53% of patients who did not achieve SVR and whose HCV variants were analyzed by population sequencing had evidence of ≥ 1 treatment-emergent amino acid substitutions in the NS3 protease domain.[4] Almost all of the detected substitutions had previously been demonstrated to reduce HCV susceptibility to boceprevir in biochemical or cell culture assays. Likewise, the results of a resistance surveillance study involving participants of phase III telaprevir trials demonstrated that 74% of patients who did not achieve SVR and who had viral population sequencing data available (n = 388) had evidence of resistant variants at the time of treatment failure (Capsule Summary).[10]
Resistance mutations detected following failure of HCV protease inhibitors typically decline in frequency following treatment discontinuation until wild-type variants once again predominate, although the available data suggest this may take many months. In a long-term follow-up study of patients treated with boceprevir plus peginterferon/ribavirin in the phase III studies, 155 patients with treatment failure and detectable resistance mutations were followed for 6-14 months after treatment was stopped. Overall, approximately 20% of patients still had resistant variants detectable by population-based sequencing at follow-up. The disappearance rate for the different NS3 protease resistance mutations was variable and is shown in Table 2.
Table 2. Proportion of Patients Without Detectable Boceprevir-Resistant Variants at Long-term Follow-up[11]
In the telaprevir resistance surveillance study described earlier, 71% of patients had only wild-type virus detected by population sequencing within 1 year after treatment discontinuation.[10] Figure 9 illustrates the loss of detectable resistance over time in patients discontinuing telaprevir plus peginterferon/ribavirin according to specific amino acid substitutions common in patients with genotype 1a and genotype 1b HCV infection. It is notable that resistance variants became undetectable more rapidly in patients infected with genotype 1b vs genotype 1a HCV in this analysis.
Figure 9. Loss of detectable resistance in patients discontinuing telaprevir plus peginterferon/ribavirin.[10]
Taken together, these studies support the role of strict adherence to the futility stopping rules for boceprevir and telaprevir to allow the return of wild-type virus and to limit the further evolution of drug-resistant variants. Failure to adhere to recommended stopping rules may increase the number of viral resistance mutations, which in turn may reduce the speed of recovery of wild-type virus and may potentially reduce future treatment
Release Date:
December 22, 2011
Just in case that link doesn't work properly I also tried to copy and paste the whole text below, with the most relevant info nearer to the end of the report, but unfortunately, the tables and figures can't seem to be pasted, and they hold much of the important info. In my own words, the study looked at how many patients who failed triple tx with Telaprevir still had drug-resistant virus variants at different periods of time after tx, looking as far out as slightly over 16 months after stopping. It shows a fairly steady decline, with essentials no mutant variations remaining at 17 months. I hope you can access the link itself.
Boceprevir and Telaprevir Stopping Rules
The case patient is a 45-year-old man who experienced treatment failure on peginterferon/ribavirin; his treatment was discontinued after 12 weeks because his HCV RNA had not decreased by 2 log10 IU/mL. He has chosen to undergo retreatment with boceprevir plus peginterferon/ribavirin. The patient is infected with genotype 1 HCV with a baseline HCV RNA level of 2.3 million IU/mL and biopsy-proven fibrosis (Ishak score: 5 of 6). He tolerates therapy well, and his HCV RNA levels are 1700 IU/mL at Week 8 and 800 IU/mL at Week 12. How should you manage this patient now at Week 12 of therapy?
Graham R. Foster, FRCP, PhD:
This patient’s medication unfortunately must be stopped at Week 12, based on the futility rules outlined for boceprevir in the US Food and Drug Administration–approved label.[4] The futility rules dictate that all therapy should be discontinued in patients whose HCV RNA levels are ≥ 100 IU/mL at treatment Week 12, as well as in those who have detectable HCV RNA at treatment Week 24 (Table 1).[1,4]
The futility rules are slightly different for patients who are receiving telaprevir plus peginterferon/ribavirin. According to the US telaprevir label, all therapy should be discontinued in patients whose HCV RNA level is > 1000 IU/mL at treatment Weeks 4 or 12, and peginterferon/ribavirin should be discontinued at Week 24 if HCV RNA is detectable (Table 1).[1,5] Thus, the case patient’s HCV RNA level of 800 IU/mL at Week 12 of therapy meets the stopping rules for boceprevir-based therapy but not for telaprevir-based therapy.
For both agents, the assays used for determining HCV RNA levels should have a lower limit of HCV RNA quantification of ≤ 25 IU/mL and a limit of HCV RNA detection of approximately 10-15 IU/mL.
Table 1. Telaprevir and Boceprevir Stopping Rules[1,4,5]
It is essential that these stopping rules be strictly observed to reduce the risk of expanding the pool of drug-resistant viral variants. In the absence of therapy, HCV exists as a heterogeneous mixture of viral variants in which the majority of the species are likely to be susceptible to direct-acting agents, because most naturally occurring drug-resistant variants have lower replicative capacity (are “less fit”) than wild-type virus. However, in patients with treatment failure on protease inhibitor–based triple therapy, drug-susceptible viruses have been largely eliminated, and drug-resistant variants with varying levels of replicative fitness predominate. Continuing therapy with a direct-acting agent in the presence of ongoing viral replication provides continued selective pressure on drug-resistant variants, promoting the selection of additional mutations that can increase their replicative fitness.
In phase III boceprevir trials, 53% of patients who did not achieve SVR and whose HCV variants were analyzed by population sequencing had evidence of ≥ 1 treatment-emergent amino acid substitutions in the NS3 protease domain.[4] Almost all of the detected substitutions had previously been demonstrated to reduce HCV susceptibility to boceprevir in biochemical or cell culture assays. Likewise, the results of a resistance surveillance study involving participants of phase III telaprevir trials demonstrated that 74% of patients who did not achieve SVR and who had viral population sequencing data available (n = 388) had evidence of resistant variants at the time of treatment failure (Capsule Summary).[10]
Resistance mutations detected following failure of HCV protease inhibitors typically decline in frequency following treatment discontinuation until wild-type variants once again predominate, although the available data suggest this may take many months. In a long-term follow-up study of patients treated with boceprevir plus peginterferon/ribavirin in the phase III studies, 155 patients with treatment failure and detectable resistance mutations were followed for 6-14 months after treatment was stopped. Overall, approximately 20% of patients still had resistant variants detectable by population-based sequencing at follow-up. The disappearance rate for the different NS3 protease resistance mutations was variable and is shown in Table 2.
Table 2. Proportion of Patients Without Detectable Boceprevir-Resistant Variants at Long-term Follow-up[11]
In the telaprevir resistance surveillance study described earlier, 71% of patients had only wild-type virus detected by population sequencing within 1 year after treatment discontinuation.[10] Figure 9 illustrates the loss of detectable resistance over time in patients discontinuing telaprevir plus peginterferon/ribavirin according to specific amino acid substitutions common in patients with genotype 1a and genotype 1b HCV infection. It is notable that resistance variants became undetectable more rapidly in patients infected with genotype 1b vs genotype 1a HCV in this analysis.
Figure 9. Loss of detectable resistance in patients discontinuing telaprevir plus peginterferon/ribavirin.[10]
Taken together, these studies support the role of strict adherence to the futility stopping rules for boceprevir and telaprevir to allow the return of wild-type virus and to limit the further evolution of drug-resistant variants. Failure to adhere to recommended stopping rules may increase the number of viral resistance mutations, which in turn may reduce the speed of recovery of wild-type virus and may potentially reduce future treatment
Release Date:
December 22, 2011
I don't doubt what saying is true. I didn't think that you could just restart incivek. I doubt the creators/makers of Incivek will support the restarting
Incivek. That in itself can be an issue. Could you post a link to the studies
you referenced. I think this is interesting - a study has been done already on the long term effects of stopping and starting incivek.
DWBH
Incivek. That in itself can be an issue. Could you post a link to the studies
you referenced. I think this is interesting - a study has been done already on the long term effects of stopping and starting incivek.
DWBH
Hi I am happy to hear that they think you can restart, that is excellent news.
I remember my doctor telling me I could not try the Incivek because of a previous tx. It was a polymerase inhibitor, not a protease, I had to explain it to him.
I am wishing you the best
I remember my doctor telling me I could not try the Incivek because of a previous tx. It was a polymerase inhibitor, not a protease, I had to explain it to him.
I am wishing you the best
That was supposed to be lab work, not jab work, though I guess it's a fitting typo!
Wow, that's amazing, and good news (I think). I've not yet heard of anyone being told by a knowledgable hepatologist that they can restart Incivek once they've stopped it. The only studies I've seen have shown that it reverts back to being a "wild" genotype after 2-3 years, and I've not seen anyone proposing restarting after such a short period. Have they done any jab work to verify that your virus is still "wild" and not mutated to a drug-resistant variety or are they planning to play it by ear and determine that by how your VL responds to restarting tx? I'm eager to hear about this and excited that you get another chance so soon. I hope your platelets can be managed better this next time. Good luck!
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