Aa
prednisone 18 day treatment and SVR
Does anyone have information about the link if any, between SVR and use of a medrol dose pak?. A dermatologist in the ER prescribed it for my rash and I dont think they consulted my hepatologist. Seems like it could lead to viral breakthrough because it lowers the immune response. Any thoughts??
In the "Advance " trial for Incivek in the group that did Incivek for 8 weeks vs. 12 the rates of SVR were:
the T8/PR group,
the overall SVR rate was 72%.
The eRVR rate was 57% and the SVR rate for eRVR subjects was 87%. The SVR rate for no eRVR subjects was 52%.
6% more patients experienced Viral breakthrough doing Incivek for 8 weeks vs. 12 weeks
The overall SVR rate was 79% in those that did Incivek for 12 weeks vs. the 72% doing 8 weeks
Given this statistic it would seem logical if one is experincing a severe rash why the protocol is to discontinue Incivek somewhat early as the success rate is not that significantly different and one might be able to continue treatment.
Will
the T8/PR group,
the overall SVR rate was 72%.
The eRVR rate was 57% and the SVR rate for eRVR subjects was 87%. The SVR rate for no eRVR subjects was 52%.
6% more patients experienced Viral breakthrough doing Incivek for 8 weeks vs. 12 weeks
The overall SVR rate was 79% in those that did Incivek for 12 weeks vs. the 72% doing 8 weeks
Given this statistic it would seem logical if one is experincing a severe rash why the protocol is to discontinue Incivek somewhat early as the success rate is not that significantly different and one might be able to continue treatment.
Will
http://www.clinicaloptions.com/Hepatitis/Annual%20Updates/2012%20Annual%20Update/Modules/HCV_Management/Pages/Page%206.aspx
Table 5. Management of Telaprevir-Associated Rash
-----------------------------------------------------------------------
Mild to Med. Rash: Con't all meds (Incivek should not be reduced or interupted)
Severe Rash: Discontinue Incivek ..cont. Peg/Riba
If no improvent within 7 days or possibly earlier : Discontinue all medications
Will
Table 5. Management of Telaprevir-Associated Rash
-----------------------------------------------------------------------
Mild to Med. Rash: Con't all meds (Incivek should not be reduced or interupted)
Severe Rash: Discontinue Incivek ..cont. Peg/Riba
If no improvent within 7 days or possibly earlier : Discontinue all medications
Will
Te protocol if a serious rash is evident then to discontinue Incivek and if this still not abate with in 7 days to stop "all medications
Will
Rash is a frequent adverse event reported by patients receiving telaprevir, with up to 56% of patients treated with telaprevir in clinical trials developing some type of rash compared with 34% in the pegIFN/RBV control arms.[2] Fortunately, only 4% of patients experienced severe rash and most cases were mild to moderate. Rash events resulted in telaprevir discontinuation in 6% of patients. A small proportion of patients (< 1%) experienced severe cutaneous adverse events including Stevens-Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS). Based on these findings, it is important that any cases of rash are carefully monitored for signs of progression or the development of systemic symptoms.[2] Although the vast majority of rashes will be mild to moderate, there is a low rate of progressive rash that requires careful management.
The management of mild to moderate rash may involve topical corticosteroids or oral antihistamines for symptomatic relief (Table 5).[2] For severe rash, telaprevir should be discontinued; if there is no improvement in the rash within 7 days, discontinuation of pegIFN/RBV should be considered.
Will
Rash is a frequent adverse event reported by patients receiving telaprevir, with up to 56% of patients treated with telaprevir in clinical trials developing some type of rash compared with 34% in the pegIFN/RBV control arms.[2] Fortunately, only 4% of patients experienced severe rash and most cases were mild to moderate. Rash events resulted in telaprevir discontinuation in 6% of patients. A small proportion of patients (< 1%) experienced severe cutaneous adverse events including Stevens-Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS). Based on these findings, it is important that any cases of rash are carefully monitored for signs of progression or the development of systemic symptoms.[2] Although the vast majority of rashes will be mild to moderate, there is a low rate of progressive rash that requires careful management.
The management of mild to moderate rash may involve topical corticosteroids or oral antihistamines for symptomatic relief (Table 5).[2] For severe rash, telaprevir should be discontinued; if there is no improvement in the rash within 7 days, discontinuation of pegIFN/RBV should be considered.
Hector,
You misconstrue my words. I wasn't implying the same thing would happen with fran or that she would definitely go on to SVR and I disagree with your statement "but to compare two patients treatment response as a 'proof of concept' is poor and misleading advice in my opinion" and also find your statement quite presumptuous.
I was not giving proof or advice, merely providing an example from another member who under very similar circumstances went on to achieve SVR and providing and example that shows SVR is possible. As far as the probability goes, as I stated in a previous post on this same thread, "it's a toss up". Neither you or I know what the outcome will be for fran and no, I will not provide proof of the statement regarding: "'Incevik does most of what it's going to do within the first 4 weeks. After that, the IFN and riba go in for the sustained deep cleansing" because those are NOT my words.
What I do know is RVR is the best indicator of SVR and I have seen people achieve SVR who were forced to stop the Incvivek early, some at wk 6, 7, 8, 9, 10, and 11 due to the rash. The key factor in all of those who went on to acheive SVR because they were UND at wks 4 & 12. In other words, the virus was UND at wk 4 and remained UND through wk 12 and there after without the Incivek. I would never suggest stopping Incivek early is a good idea, adherence to full treatment protocol gives the best possibility of SVR, however, it is irrefutable and on record that SVR is possible if one is RVR and forced to stop the protease inhibitor early.
You misconstrue my words. I wasn't implying the same thing would happen with fran or that she would definitely go on to SVR and I disagree with your statement "but to compare two patients treatment response as a 'proof of concept' is poor and misleading advice in my opinion" and also find your statement quite presumptuous.
I was not giving proof or advice, merely providing an example from another member who under very similar circumstances went on to achieve SVR and providing and example that shows SVR is possible. As far as the probability goes, as I stated in a previous post on this same thread, "it's a toss up". Neither you or I know what the outcome will be for fran and no, I will not provide proof of the statement regarding: "'Incevik does most of what it's going to do within the first 4 weeks. After that, the IFN and riba go in for the sustained deep cleansing" because those are NOT my words.
What I do know is RVR is the best indicator of SVR and I have seen people achieve SVR who were forced to stop the Incvivek early, some at wk 6, 7, 8, 9, 10, and 11 due to the rash. The key factor in all of those who went on to acheive SVR because they were UND at wks 4 & 12. In other words, the virus was UND at wk 4 and remained UND through wk 12 and there after without the Incivek. I would never suggest stopping Incivek early is a good idea, adherence to full treatment protocol gives the best possibility of SVR, however, it is irrefutable and on record that SVR is possible if one is RVR and forced to stop the protease inhibitor early.
this is only my experience, but i had to stop the incivek at 10 weeks and then was placed on prednisone at week 11 and was on prednisone for 5 weeks. i was undetected from week 4 until the end of treatment. no breakthroughs. i posted photos of the rash on my profile. the first photo was taken immediately a few hours before the first dose of prednisone. the clobetasol helped some, but without the oral steroids i would not have been able to continue.
eric
eric
coraggio,
One person's experience should not be used as an example for others to follow. The data is clear. All the stats we have for the effectiveness of triple therapy with Incivek is based on 12 weeks of Incivek treatment. Not following proper treatment protocols makes all data from clinical trials not applicable. So we can not predict the chances of SVR for Fran. Of course we all wish her well, but to compare two patients treatment response as a 'proof of concept' is poor and misleading advice in my opinion.
'Incevik does most of what it's going to do within the first 4 weeks. After that, the IFN and riba go in for the sustained deep cleansing.'
- Please post the reference source for this statement. And any medical paper that says anything about 'sustained deep cleaning'.
Why do patients treat for 12 weeks? Because that was the duration found to be most effective to achieve SVR.
The actual fact is that the wild virus exists beyond week 4 even if undetectable. In fact it exists beyond week 12 but at that time the majority of virus is variants. Why is Incivek stopped at week 12? Because the antivial Incivek mostly acts upon the wild virus not the variants. The peg-interferon and ribavirin are then needed to eliminate the variants.
Resistance in the Era of HCV Protease Inhibitors
Antiviral drug resistance and the battle for a cure below the limit of detection
Ann Kwong, PhD
CDC Symposium
“Identification, Screening and Surveillance of HCV Infections in the Era of Improved Therapy for Hepatitis C”
December 1, 2011
Atlanta, GA
http://www.cdc.gov/hepatitis/Resources/MtgsConf/HCVSymposium2011-PDFs/12b_Kwong.pdf
Resistant variants are present before treatment
• Plasma contains ~ 1,000,000 HCV per mL
• In most patients, naturally occurring resistant variants are below the limit of detection for sequencing (~1,000 HCV per mL)
• Most resistant variants are very unfit and are not detected prior to therapy
• Patients with detectable resistant variants prior to therapy are rare (<2% each)
• Resistant variants are selected during treatment
• Potent antiviral therapy eliminates sensitive variants
• Resistant variants are uncovered which can then expand
• Clinical resistance occurs if drug levels are too low to inhibit viral replication AND if resistant variants are fit and replicate
Characterization of variants associated with viral break through (BT) on telaprevir (wks 1-12) in ph3 studies
• Viral BT is associated with higher-level resistant variants which
cannot be suppressed by clinically achievable levels of TVR
• T/PR suppresses WT and lower-level resistant variants
• Virologic failure is likely due to an insufficient PR response
Telaprevir + Peg-IFN/RBV clears most wild-type and lower-level resistant HCV variants in the first 12 weeks
• Continued Peg-IFN/RBV is necessary to clear the remaining virus
Good luck Fran!
Hector
One person's experience should not be used as an example for others to follow. The data is clear. All the stats we have for the effectiveness of triple therapy with Incivek is based on 12 weeks of Incivek treatment. Not following proper treatment protocols makes all data from clinical trials not applicable. So we can not predict the chances of SVR for Fran. Of course we all wish her well, but to compare two patients treatment response as a 'proof of concept' is poor and misleading advice in my opinion.
'Incevik does most of what it's going to do within the first 4 weeks. After that, the IFN and riba go in for the sustained deep cleansing.'
- Please post the reference source for this statement. And any medical paper that says anything about 'sustained deep cleaning'.
Why do patients treat for 12 weeks? Because that was the duration found to be most effective to achieve SVR.
The actual fact is that the wild virus exists beyond week 4 even if undetectable. In fact it exists beyond week 12 but at that time the majority of virus is variants. Why is Incivek stopped at week 12? Because the antivial Incivek mostly acts upon the wild virus not the variants. The peg-interferon and ribavirin are then needed to eliminate the variants.
Resistance in the Era of HCV Protease Inhibitors
Antiviral drug resistance and the battle for a cure below the limit of detection
Ann Kwong, PhD
CDC Symposium
“Identification, Screening and Surveillance of HCV Infections in the Era of Improved Therapy for Hepatitis C”
December 1, 2011
Atlanta, GA
http://www.cdc.gov/hepatitis/Resources/MtgsConf/HCVSymposium2011-PDFs/12b_Kwong.pdf
Resistant variants are present before treatment
• Plasma contains ~ 1,000,000 HCV per mL
• In most patients, naturally occurring resistant variants are below the limit of detection for sequencing (~1,000 HCV per mL)
• Most resistant variants are very unfit and are not detected prior to therapy
• Patients with detectable resistant variants prior to therapy are rare (<2% each)
• Resistant variants are selected during treatment
• Potent antiviral therapy eliminates sensitive variants
• Resistant variants are uncovered which can then expand
• Clinical resistance occurs if drug levels are too low to inhibit viral replication AND if resistant variants are fit and replicate
Characterization of variants associated with viral break through (BT) on telaprevir (wks 1-12) in ph3 studies
• Viral BT is associated with higher-level resistant variants which
cannot be suppressed by clinically achievable levels of TVR
• T/PR suppresses WT and lower-level resistant variants
• Virologic failure is likely due to an insufficient PR response
Telaprevir + Peg-IFN/RBV clears most wild-type and lower-level resistant HCV variants in the first 12 weeks
• Continued Peg-IFN/RBV is necessary to clear the remaining virus
Good luck Fran!
Hector
This post was from a member called mremeet who had a horrific rash from the Incviek. Looks like he was in the VX-950 trials. He was in bad shape and had no other choice but to take the steroids to counter the rash. If it's any consolation, he was put on IV steroids in the ER because he was a total mess and then took a multitude of oral steroids to counter the rash. Topical steroids weren't strong enough and as you can see he still went to SVR.
mremeet
Feb 01, 2012 .To: mellie25.
I got the bad rash on Incivek too (it was called VX-950 when I was taking it). The rash started coming on strong by about week 5, same as you. It really turned into a debacle for me and I had to discontinue by week 6 or thereabouts. I went on to SVR fine after 40 weeks of treatment, much of it with substantially reduced ribavirin dose too. And not only that, but I also took a lot of immunosuppressants (prednisone and solumedrol) to control the rash while I still had it, whcih serves to weaken the effect of the aitniviral drugs.
Yet I STILL SVR'ed.
Incevik does most of what it's going to do within the first 4 weeks. After that, the IFN and riba go in for the sustained deep cleansing. If you continue to take the Incivek, your rash could explode into a serious health condition that may result in the early termination of your treatment. It almost happened to me and several other study participants during our PROVE 1 drug trial (before it was FDA approved).
If I were you, I'd have no problem stopping the Incivek after 8 good weeks of it. Especially if you're maintaining full dosages of IFN and riba. In my opinion you're doing fine and should have a great chance of going on to SVR later without the Incivek from this point on.
Best of luck. .
mremeet
Feb 01, 2012 .To: mellie25.
I got the bad rash on Incivek too (it was called VX-950 when I was taking it). The rash started coming on strong by about week 5, same as you. It really turned into a debacle for me and I had to discontinue by week 6 or thereabouts. I went on to SVR fine after 40 weeks of treatment, much of it with substantially reduced ribavirin dose too. And not only that, but I also took a lot of immunosuppressants (prednisone and solumedrol) to control the rash while I still had it, whcih serves to weaken the effect of the aitniviral drugs.
Yet I STILL SVR'ed.
Incevik does most of what it's going to do within the first 4 weeks. After that, the IFN and riba go in for the sustained deep cleansing. If you continue to take the Incivek, your rash could explode into a serious health condition that may result in the early termination of your treatment. It almost happened to me and several other study participants during our PROVE 1 drug trial (before it was FDA approved).
If I were you, I'd have no problem stopping the Incivek after 8 good weeks of it. Especially if you're maintaining full dosages of IFN and riba. In my opinion you're doing fine and should have a great chance of going on to SVR later without the Incivek from this point on.
Best of luck. .
Curious question - the medrol dose pack I'm familiar with is given over a period of six days. What is the reference to an 18 day treatment???
Topical steroid are fine, in my opinion.
My earlier response was about taking them orally.
Hope your rash clears up quickly.
My earlier response was about taking them orally.
Hope your rash clears up quickly.
I just read your other thread and see why the incivek was stopped. Again, you should be okay with Medrol but check with your Hepa to be sure.
Argh this site keeps freezing up on me and I can't access your profile. Forgive me if I am mistaken but didn't you stop the Incivek on week 8? If so at this point I would think your rash will clear up more and more as time passes.
I agree with what has been said so far. I think you need two things to manage the rash: A topical steroid cream and an oral antihistamine.
Both Fluocinolone acetonide & Triamcinolone acetonide are considered class 3: moderate (2-25 times as potent as hydrocortisone). Something like Cobetasol is Class 1: very potent (up to 600 times as potent as hydrocortisone).
I would ask your Hepa for an Rx for one of these in addition to an antihistamine like Hydroxizine.
http://dermnetnz.org/doctors/dermatitis/corticosteroids.html
I agree with what has been said so far. I think you need two things to manage the rash: A topical steroid cream and an oral antihistamine.
Both Fluocinolone acetonide & Triamcinolone acetonide are considered class 3: moderate (2-25 times as potent as hydrocortisone). Something like Cobetasol is Class 1: very potent (up to 600 times as potent as hydrocortisone).
I would ask your Hepa for an Rx for one of these in addition to an antihistamine like Hydroxizine.
http://dermnetnz.org/doctors/dermatitis/corticosteroids.html
Topical steroids are fine. If you have a rash, I would recommend getting a prescription steroid ointment or cream or solution (fluocinonide ointment, Clobetesol soln., and some others) and also a prescription for an oral antihistamine. Hydroxyzine (Atarax) works well usually. If your rash is bad, the over the counter stuff is not going to work. Plus, one needs to get on top of the rash immediately because it can and will snow ball.
You are off Incivek now aren't you? If you are off Incivek then you should be okay with whatever they gave you in the ER (but ask your hepatologist first). If you are still on Incivek then oral steroids are not recommended (as noted by others).
I am curious why they took you off Incivek. Was it due to the rash?
Just for the record, I used Hydroxyzone pills 50 mg every six hours. Also Clobetesol soln and fluocinonide ointment. All 3 are prescriptions. The Hydroxyzone was the thing that finally controlled the rash and itching. The topicals helped with itching and eventually they would clear the rash (after 3-4 weeks), but they worked only where I put them. Then the rash moved next door.
You are off Incivek now aren't you? If you are off Incivek then you should be okay with whatever they gave you in the ER (but ask your hepatologist first). If you are still on Incivek then oral steroids are not recommended (as noted by others).
I am curious why they took you off Incivek. Was it due to the rash?
Just for the record, I used Hydroxyzone pills 50 mg every six hours. Also Clobetesol soln and fluocinonide ointment. All 3 are prescriptions. The Hydroxyzone was the thing that finally controlled the rash and itching. The topicals helped with itching and eventually they would clear the rash (after 3-4 weeks), but they worked only where I put them. Then the rash moved next door.
Fran was taken off Incivek last Friday due to rash. I believe it was her 8th week so there should not be any drug interaction.
Fran, the rash should subside somewhat from discontinuing the Incivek but from what you describe you have no other choice but to take the steroids and get the rash under control. Unfortunately, you were in the minority of those who experiece severe dermatological pruritus and rash. I don't think a short course of steroids will have an impact. My concern would be that you had to stop the Incivek early along with the riba reduction but it's coin toss so get that rash under control and keep moving forward.
Fran, the rash should subside somewhat from discontinuing the Incivek but from what you describe you have no other choice but to take the steroids and get the rash under control. Unfortunately, you were in the minority of those who experiece severe dermatological pruritus and rash. I don't think a short course of steroids will have an impact. My concern would be that you had to stop the Incivek early along with the riba reduction but it's coin toss so get that rash under control and keep moving forward.
But what do you think about the topically applied corticosteroids- like triamcinolone
I hate prednisone and consider it vastly over prescribed.
I'd try something else for your rash before starting that nasty stuff.
I'd try something else for your rash before starting that nasty stuff.
As Jules mentioned, if you are using telaprevir, you shouldn't use the medrol pack due to the interaction with corticosteroides. To help manage the rash, several on the forum have used hydroxyzine (atarax) with good results. You should discuss a rash management plan with your hepatologist.
I was on Inf/Riba only and was able to use the medrol dose pack which made a huge difference. It did make me nervous though.
http://hepatitiscnewdrugs.blogspot.com/2012/03/iincivek-help-recognizing-rash.html
I was on Inf/Riba only and was able to use the medrol dose pack which made a huge difference. It did make me nervous though.
http://hepatitiscnewdrugs.blogspot.com/2012/03/iincivek-help-recognizing-rash.html
Interactions between your selected drugs
prednisone ↔ telaprevir
Applies to: prednisone, Incivek (telaprevir)
GENERALLY AVOID: Coadministration with telaprevir may increase the plasma concentrations of systemic corticosteroids. The mechanism involves telaprevir inhibition of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of most steroids. No pharmacokinetic data are currently available, although telaprevir is a potent CYP450 3A4 inhibitor and may interact significantly.
MANAGEMENT: The use of systemic corticosteroids in combination with telaprevir is not recommended. Systemic corticosteroids should not be used to treat telaprevir-induced rash.
prednisone ↔ telaprevir
Applies to: prednisone, Incivek (telaprevir)
GENERALLY AVOID: Coadministration with telaprevir may increase the plasma concentrations of systemic corticosteroids. The mechanism involves telaprevir inhibition of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of most steroids. No pharmacokinetic data are currently available, although telaprevir is a potent CYP450 3A4 inhibitor and may interact significantly.
MANAGEMENT: The use of systemic corticosteroids in combination with telaprevir is not recommended. Systemic corticosteroids should not be used to treat telaprevir-induced rash.
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