Telaprevir Rash

For any of you who suffered with a rash/itch in the telaprevir trials, can you share what worked to help you? I got the go ahead to try treatment again which was a huge surprise to me. I never thought my hematologist would allow it after my neuts dropped to zero but he said I could. Strangely enough, that happening again does not scare me as much as an itchy rash. I have had some horrible experiences with rashes from other non-related drugs and that itch is worse than pain. How bad did it get and did anythng help to take the itch away?

[dointime]

You are right to be concerned about the tela rash as it can be a showstopper.  Best thing is to get a dermatologist on standby just in case.  I needed heavy duty Elocon cream to control my rash.  It was really scary.  The itch never really went away, nor did the rash.  I did 12 weeks tela and was about at the end of my endurance by that time.
http://en.wikipedia.org/wiki/Mometasone_furoate

Hey, if you are the Susie I'm thinking of from the other board, I'm so pleased to hear this great news that you will be able to treat again.  Really, you so deserve a break. and I wish you all the best

dointime      

[copyman]

Hi Susie,

Great news that you got the go ahead for another round of TX (lucky you ) I wouldn't worry to much about the rash.

I did get some itching from the Telaprevir but not the dreaded rash I had read about.

I do believe Vertex addressed the issue after the Phase II studies. It really wasn't a big problem in the Phase III study.

If you look at the data there were a lot less dropouts in the phase III study do to the rash.

Looks like Telaprevir knew they had to address that issue to get FDA approval.

best of luck

[willing]

Best of luck with your plans. How come you opted for the tela vs the two DAA combo (eg BMS or Vetex) that you were considering earlier?

Unfortunately I can't see much reason to support copy's optimistic outlook. If you're lucky enough not to get hit by it that's great - but it certainly seems many/most are and find it a major hurdle. Here's one of  several earlier threads on the topic:
http://www.medhelp.org/posts/Hepatitis-C/VX-Rash-Victims---speak-up-please/show/291263

Also from abstract 1935 at AASLD'10 "Adverse Event-Related Treatment Costs Associated with Protease Inhibitor-Based Combination Therapy for Hepatitis C "
Their projected  estimates for tela triggered rash intervention are 61% for T12PR48 and 54% for T12PR24.

As for Vertex having fixed this between Phase II and III - this makes no sense. If it hadn't been the same drug the FDA would have made them start over. From the final phase III ILLUMINATE data  discontinuation due to tela adverse effects was over 17%.

I'm also quite worried about this as I had major skin troubles on my last round. The only silver lining I can see on the horizon is that if the anemia hits hard enough you don't have enough energy to itch a lot - the more comatose the better!

BTW - that  abstract 1935 includes a funny line on the costs of all this joy: "Average costs to manage an AE episode were estimated at up to $4825 for anemia (assuming epo use rate of 22%), $2837 for depression, $566 for diarrhea, and $633 for rash" . (I bet on sale you can find the diarrhea for a lot less...). Patients are going to hate the rash but inscos will love it (relative to epo).

[nygirl7]

I remember too that they said they had done something to greatly relieve the way the rash was to how it is now.  It sounds more like regular ribarash now compared to what it sounded like before (impossible). I remember reading it as well copyman you aren't crazy (well maybe a little or at least we are crazymen together ;)

Good luck to you Susan I think I remember who you are too and wish you well with this treatment.  As copy said he didn't even really have the rash so  perhaps you will get lucky too!

[Andiamo1]

I think willing must be correct; they couldn't have changed the drug.  My guess is that they recognize it earlier on and treat it with topicals to prevent it from getting out of hand.

[nygirl7]

I wish I knew how to look for it because I remember reading it too.  Maybe it was someone supposition or something but it was posted in here at one time. Probably someone taking tele assumed so.

We are not crazy ;)

[fretboard]

No not the drug itself but they could have changed some of the inert ingredients or buffereing agents that have nothing to do with the API=Active Pharmaceutical Ingredient but could have affected the metabolism factors.      

Good luck to you Suzie2010!!

[SusieS2010]

Thanks so much for the information. Dointime, I'm not sure which board you are speaking of. I have visited a few but this one seems to have the best hep C educated patients wiho have tons of experiences to share. Copy, that is great to know that fewer patients dropped out due to rash in Phase 3. I don't care whether they changed something or just figured out how to treat the rash, I'll take it. Willing, when I talked to Dr. Graham at Vertex she explained that genotype 1b's are the patients who will be able to do the DAA combos because their mutations are so weak that after trying telaprevir, if it doesn't work, the resistance will be gone in 2 years. So, why not? If it works great. If not, there is always the DAAs.

Thanks to all for your good wishes. I don't know what will happen with my virus but I'm pretty sure my neutrophils will be undetected.

[copyman]

You are right NYG I remember also reading about Vertex making some changes to the drug.

Susie,
Take it for what it is worth, I was in a Telaprevir study and was very concerned about the rash.
I was told first hand by a doctor that works closely with Vertex that the formula was "tweeked" to help prevent the rash from hell.

Of course people still had some derm problems but not as severe as phase 1 & 2. I'm sure some in the placebo group even had rash problems and dropped out with just the Riba.

[dointime]

"when I talked to Dr. Graham at Vertex she explained that genotype 1b's are the patients who will be able to do the DAA combos because their mutations are so weak that after trying telaprevir, if it doesn't work, the resistance will be gone in 2 years."

Well that is pretty interesting to me as I am a 1b who failed with telaprevir and had mutations.  Did Dr Graham say what evidence there is for this?  Has Vertex done a study on it which is available to the public?

dointime  

[willing]

dointime: check out AASLD abstract 227 "Long-term Follow-up of Patients with Chronic Hepatitis C Treated with Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin: Interim Analysis of the EXTEND Study ".

"Amongst patients who did not achieve SVR after telaprevir-based therapy variants associated with decreased sensitivity to telaprevir were no longer detectable in 89% of patients within the study period. "
---
I'm not sure I  trust the completeness of the resistance test they applied:

"Viral sequence was determined by nested RT-PCR followed by population sequencing of the NS3 protease (detecting variants present in >~20% of viral population). Amino acid (AA) positions 36, 54, 155, and 156 that are associated with decreased susceptibility to TVR in genotype 1 HCV patients were analyzed. We report on patients who possessed identified variants with decreased susceptibility to TVR at time of treatment failure."

In particular minority strains (under 20%) seem like they could still present a resistance challenge. Also they did nothing to check for in-vitro efficacy of re-tx with tela among those patients. One of my gripes with Vertex is that I believe they should be making this test available to EVERYONE that failed tela tx. Also check out that abstract I posted in GFRY's thread - it look like resistance mutations could actually be a plus for re-tx.

Copy/NYG: if you can find any evidence supporting improvement in rash effects please post it. That would be good news indeed!

I suppose they are at liberty to change the inert ingredients (these can vary between manufacturers of the same drug) but the whole point of fillers is that they're designed to be inert. Unless Vertex got the fillers wrong in their early batches it's hard to see how this could make any difference.  

[Willy50]

For what it's worth I have never heard Vertex talk about tweaking the formula.

The only thing that I have heard them refer to was improved rash management protocols.
That would mean improved treatments of the rash using and better understanding of where dose reduction was required, stop dosing and return to dosing protocols were most effective.

Willy

[SusieS2010]

Dointime, Dr. Graham, if I remember correctly, said there has not been a definitive study on this. Ya know, I've been trying to treat this virus since 1992. I've done a gazillion units of interferon from mono treatment to triple treatment (Zadaxin). I've had HCV for 44 years and I've been cirrhotic since my first biopsy in 1992. I'm also a 66 year old grandma. I've gotten to the point where I am totally on information overload and when Dr. Graham suggested not waiting for the protease/polymerase, non-interferon trials, I didn't even bother to ask her any questions. By the time those trials get to where I would be interested, I'm sure I would be excluded because of my age. Most trials take patients up to the age of 65. When she told me that the majority of genotype 1b patients can re-treat later because the mutations usually go away, I didn't question her. I just decided to do it. Call me naive, but I've been to many meetings where she has spoken and I tend to believe what she says. She has been honest and upfront with us since I've met her.

Copyman, I do believe what you are saying and I am really relieved to hear that. What did you do about the itch? Did you just suffer with it or were you able to find something that helped?

Willing, your knowledge and understanding of this science type stuff amazes me. Good for you. I'll have to look at GFRY's thread and try to see why you say that resistance might be good for re-tx.

[copyman]

The itch wasn't that bad. I used all the things mentioned on this forum, gold bond lotion, oatmeal baths, warm water NOT hot when showering / bathing. At the one thing that gave me the most relief was a prescription for Atarax.

I have a good feeling that you will beat the Dragon next time you treat.

[SusieS2010]

Thanks Copy. I forgot all about how good atarax is. And thanks for your good feelings. I wish I were as sure as you.But I gotta try, At the end of the day, at least I know I tried everything I could.

[desrt]

"Once more into the fray." Good Luck Susie.
E

(You and Miles and Zadaxin. You have indeed "tried everything".)

[SusieS2010]

Hi desrt. It is great to see you. Yes, Miles and I plan on being treatment buddies once again. We've tried it all up to these newer drugs.The absolute worst was high dose daily infergen. Thought that was going to kill me.

I hope you and your family have a great Thanksgiving.

[pcds]

I have been concerned about the rash, having suffering with just Riba rash and wondering how much I could endure further.  I've had the virus for 40 yrs and have very minor liver effects, may have been the drinking not the virus, I don't know.  Part of me wants to start tx as soon as Telaprevir becomes available. Part of me thinks I should wait and see how it's working and how people as being tx for the side effects.  Especially here where so much information is available.  Then I wonder,  this tx can cause me more harm then my slow acting HCV.  

[SusieS2010]

I guess there is always the chance that someone can have some lasting side effects. But it seems pretty rare to me. It depends on how badly you'd like to get rid of the virus.

BTW, I need to point out that Dr. Graham did not give me suggestions or advice. I used the wrong word. She gave me things to discuss with my treating doctors and that is how I made my decision to go ahead when telaprevir is approved rather than waiting for the DAAs.

[dointime]

I see that you have made up your mind to go with the tela tx, and that you have very good reasons for wanting to treat as soon as possible.

I just think that your planB - try again to use an NS3 protease inhibitor in a few years because the mutations go away - is based on shaky grounds.  I think that it is far from clear just what is likely to happen when the first batch of tela-resistant people get round to retreating with a similar ns3 PI.

As I already have (or had) resistant mutations I watch this space closely.  Ideally, when I treat again I want to be sure that I have something that will kill my mutations.  I wouldn't go through it again on a wing and a prayer that they had played nice and exited the building of their own accord.  After all, they were probably there in my quasispecies before tx so why would they not stick around.

I get that in your situation you want to treat as quickly as possible.  But I don't think you should rely on Dr Graham's rather glib fallback plan.

dointime    

[pcds]

Telaprevir is not a cure, it's not 100% that is for sure.  We all hope to not be the 15-20% who don't clear.  I wonder if the genetic test now available would shed some light on why the drug wasn't successful.

[dointime]

Willing, I looked up your post to GFRY

"the patient-valuable bit of insight here is that if you fail tela/boce tx the time to jump back on the bandwagon is SOON, while most circulating virus are still genetically-challenged descendants of  a few NS3A resistant clones (the genetic bottleneck) and before WT returns to dominance (but obviously you'll have to hit them with something other than tela/boce).  "

I stopped tela after 12 weeks having been UND then having a breakthrough at 15 days.  I then went straight on to SOC.  At that point I supposed that I only had resistant mutations in my viral population and that the SOC would make short work of them.  My vl was only 100,000 of less fit mutants so I figured a massacre must be assured  But it did not turn out that way.  I became UND again then had another breakthrough.  

I think that without the pressure of the NS3 protease inhibitor the mutant virus can very rapidly remutate to whatever new tx it meets.  I think that that would be the one and only reason for continuing with an NS3 PI after resistance had developed, ie. to pin the virus down in it's weakened mutated form while commencing to attack it with something else.  As far as I know, this has never been tried.  It just makes sense to me.

dointime        

[willing]

I suspect the likely problem was a poor ifn response. First the ifn was not enough to hammer the PI resistant mutants into oblivion (hence the breakthrough) and later, after the PI stopped, it was inadquate to control the remaining mutants and the returning wild type. Have you had an IL28B?

In addition one, very direct, way to assess your ifn response is to get your Dr. to write an rx for a single shot. Measure VL before shot, at 48h (to measure 1st phase decline) and at day 7(  to measure 2nd phase decline). Unlike IL28B there's no guessing there - that *is* the ifn response you  have to work with, which could help plan future tx.

Also, if you haven't already contacted Vertex about access to the test they ran as part of EXTEND it may be worth doing. Not sure that test conclusively says anything about what re-tx with a PI will do, but it's useful info. Agreed that the best strategy would be to hit residual resistant virions with something to which they don't have immunity, but in the usual PI +SOC scenario there are  no other weapons at hand...  

[dointime]

Hi willing - thanks for this response.  Yes, I agree it was probably poor ifn response.  Interesting way you suggest to measure it.  I'll run that by my doc.  I am planning on getting the IL28B at some point before my next tx.

But on the basis of what I already know I'll be waiting until the weapons are at hand to commit genocide on my whole viral population.  That sounds like a tall order but I am encouraged by the success of the polymerase inhibitors like R7128.  As you know, early indications are that they might work even when ifn response is weak, and that resistant mutations are less likely.

dointime

      

[willing]

It'll be interesting to see whether the Phase III trials for BMS-790052 and R7128 are structured to compare the new drugs  as added to SOC or SOC with PI. It's hard to imagine the FDA finding any reason to send tela back to the drawing board given the results available (only that single case of life-threatening rash which apparently could not be pinned to the tela). Merck may have a bit more trouble on account of the anemia. Assuming approval, the defn of SOC changes to rbv/ifn/PI. The new drugs could be tested in addition to those three or instead of the PI. Let's hope it's the former.  

[nygirl7]

For what it's worth I have never heard Vertex talk about tweaking the formula."

This was way way back when we were still calling it VX-950 - unfortunately I dont think the archives go back all the way to this point I think (who knows my brain is not what it used to be) that it was before they switched the site over to this current site and is before the archives.
I wish I could find it but I certainly remember something about it. At the time I was on regular tx and was mystified at how people were putting themselves through that rash when I couldn't even handle the ribarash rash.
It was the telerash and it was bad from what I read at the time - nothing like riba(interferon) rash at all.

[copyman]

You are correct Deb. It was back when I first became a MH member. I think one of the members with the rash from hell was mrmeet. The drop out rate was very high at that time. After that phase of the study the rash became less and less with considerably less drop out's. It is obvious that Vertex "tweaked" the drug to minimize the rash. At this point I don't think it is even a factor. Almost the same % of people that get the standard riba rash.

[willing]

well, I'm all for wishful thinking when all else fails, but it would be easier to believe the "tweaking" story  if  it was supported by some shred of evidence.

Many of the posts from the tela phase 2 studies are only from 2007  and are definitely still part of the archives: eg

http://www.medhelp.org/posts/Hepatitis-C/Prove-3Taking-myself-off-the-treatment/show/100917
http://www.medhelp.org/posts/Hepatitis-C/Vertex-Prove2-UK-trial--rash-strikes-in-week-2/show/96174?forums=forums
http://www.medhelp.org/posts/Hepatitis-C/VX-Rash-Victims---speak-up-please/show/291263

Any news on corrections to the problem would be more recent and thus  still  available. As to discontinuation rates due to adverse effects, as noted above Vertex reported 17.4% for the phase III ILLUMINATE trial, part of what they just filed  with the FDA.
"94 pts (17.4%) had permanent discontinuation of all study drugs (D/C) for AEs."
from AASLD'10 abstract LB2.

[copyman]

Was that 17.4 % for only rash / derm problems or all side effects?

[susan400]

I'm glad to hear what they said about the resistance thing and after 2 yrs it not being so much of an issue however, the rash thing..., tweaked, or not tweaked, don't make any difference to me, I still won't retreat with Telaprevir.  It's been 2 yrs 5 mon. since I last treated.  I'm not really doing all that bad quite frankly.  I have mixed feelings about going through treatment again.  On one hand, do I want to take my chances that the Hep will start progressing?  Or do I want to just say, skip it and live my life w/o the hassle and upheavel of another treatment?  On top of that, I have no way to pay for the Boceprevir (which is what I'll be doing), when and if it ever gets approved.  Susan400

[Magnum]

Funny you should mention the rash. Yesterday I had 6 Esophageal Verices banded and the doctor does NOT want me on Telaprevir because of the rash. He said that he recently went to a conference where they were discussing just that problem with Tela and the 10% drop-out rate because of the awful rash.

This is a tough decision for me because I want to jump on the wagon of the first PI released, but then again, I don't want to suffer for a couple of months just to be told to stop because of the rash.

On the other hand, Boceprevir present another problem... Anemia. But, since I did not have an Anemia problem through 4 failed treatment attempts, he feels I should wait a little longer if necessary, until Boce is released. Decision, decisions, decisions...

Magnum

[dointime]

On this forum it was found that people with light skin and blue eyes were the ones that got the rash.  Nobody with dark hair and eyes got the rash that I can remember here.  Please correct me if anybody knows different.  In my study group it was myself and one other out of 9 that got the rash.  I have fair hair and green eyes.  She had fair hair and an english rose complexion.  

So if you are dark I'd gamble on the tela.  If you are fair then you are warned.

dointime.

[SusieS2010]

Aarrgghhh. I have green eyes and fair skin. Bummer. Magnum, the only thing I can say is that the first stopping point will be at 4 weeks. If the viral load is not below 100, they will recommend stopping treatment at that time because the rate of SVR for those people is quite low. I figure I can do anything for a month.

[Magnum]

Point well taken, but what about the insurance company that will pay for your meds? Are they going to have second thoughts about approving a different PI? Hmmmm..


Mag

[susan400]

I have light brown hair and hazel eyes, but very fair skin.  It's that Irish/Icelandic/Scottish heritage probably.  I happen to know for a fact that it was the Telaprevir and not the Riba, since I had no Riba in the equation w/Prove 3-Group C randomization.  It was horrific and it came on rather quickly I might add.  I got it 2 wks into the treatment, which is very earlier onset compared to some of the others who got the rash.  A rash doesn't begin to describe it.  It was welts/hives, looking like I stuck my arms and upper body into a tub of scalding water because of the blistering look to it.  

Susan400

[Magnum]

Maybe you can ask your doctor if you can also wait for Boce, as it should be released not long after Tela?

Mag

[dointime]

I am Scottish / Irish too and got the tela rash at 2 weeks into tx.  I had to put those camping ice packs on my neck and chest and tie them on with bandages to numb the fire on my skin.  It was beyond imagination.

dointime
  

  

[willing]

copy: total discontinuation in all ILLUMINATE arms was 94 out of 540 pts so 17.4% (all arms all reasons). Discontinuation numbers for SOC trials are typically lower - around 8-9%. Discontinuation due to rash was much smaller - but they only give stats during  tela dosing "Treatment D/C due to anemia and rash were 3 (0.6%) and 6 (1.1%) pts, respectively, during the telaprevir treatment phase"  (from abstract LB2)

all: very interesting about rash being associated with complexion/hair color! It seems frustrating that we have to discover these trends by comparing notes with other lab rats.

If there was any truth to Vertex's being compassionately interested in patient welfare they would be working on more complete disclosure of negatives associated with the drug, now that all data are filed,  rather than on  sending Ambassadors forth to help sell more tela. We still know very little about the 1/3 of patients who didn't eRVR with ILLUMINATE (what SVR rate? what IL28B? what ifn response?) nor about the prospects of those who failed tela tx (why are the tests applied in EXTEND not available to all who developed resistant mutations?) nor about specifics of the rash (other than it will affect about 60% of pts).

[txgirl360]

I just got kicked out of the Tela study, week 4 - no rash at all, no itching.  Just not a responder. VL was 298,000.  It didn't make me sick other than just tired.  I am glad to find this discussion tho, because I have no idea what to expect next.  Any thoughts?

[cieritaqt]

I am going to start in August. I am also worried about the rash from Telaprevir. I guess I should just take the side effects as they come. I hope I don't get a rash on my face.... and positive suggestions from anyone?

Thanks

[susan400]

Hello.  I also was kicked out of a Telaprevir trial almost 4 yrs ago, in the Prove 3 trials.  I was randomized into the group C, which only got Peg and Telaprevir and no Riba.  I did get the huge rash at week 2 though.  I was kicked out on week 5, based on my week 4 blood draw.  It wasn't because of the rash that I was kicked out.  I was kicked out because I didn't clear by week 4.  Unfortunately, now, you are in the group of people who have been exposed to Telaprevir, but did not clear.  Your best bet for now, would be to give yourself some time to clear out of the Telaprevir and then, speak with a very knowledgeable hepatologist (usually these guys-the experts-are found at a large University or teaching hospital).  When we are exposed to a P.I.  (i.e. Protease or Polymerase - Inhibitor), and then, do not clear, it is harder to find resources with regard to retreatment.  I'm not trying to be negative, or tell you to give up.  I haven't.  It's just that for me, every time I tried to get into any clinical trials after my Telaprevir exposure, I was given the label of 'non-responder/Telaprevir failure patient' and so many of the trials won't accept a patient who is a Telaprevir failure patient.  I have had to wait for almost 3 yrs before I finally was able to get into this trial that I have just started on 6/22/2011.  Do you have the results to a IL28B test?  If so, are you at 'TT' allele?  I just had that test done on me on 6/22/2011 and I won't find out the results until sometime about 3-4 weeks from now.  My doctor at the trial said that he is fairly certain that I'll be a 'TT' allele since I've been so hard to get clearance.  Anyway, do you have very much damage?  If you are an early stage and don't have much damage, it might be best to wait for a couple of years and see if any more trials come up that will accept Telaprevir failure patients.  I am pretty sure that there will be more Telaprevir failure patients cropping up down the road because it is not a 100% guarantee of cure.  Anyhow, I wish you only the best and I just want you to know that I completely understand how you feel.  Susan400

[willing]

it's now 6 months since the post above griping about lack of data from Vertex on key tx information. The information they  released for the FDA advisory review

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM252562.pdf

filled in a couple of  gaps.  Interesting to look back and see what is now available.

-  SVR response among non eRVRs.  This is relevant  to anyone that doesn't show UND after 4W of INCI . From page 54 of the Vertex FDA submission describing results from study 108 (ADVANCE)

"SVR24 rates for subjects in the T/PR groups who did not have eRVR and received 48 weeks treatment ranged from 52% to 60%."

By contrast, the control SOC group showed 42%. The low 52% number is from an 8W of PI arm which will not be used in practice so the 60% is more relevant. The results from ILLUMINATE (Study 111) were a bit better. There, SVR among non- eRVRs reached 66% (page 74). Overall even for those who don't make the w4 UND cutoff, odds still look pretty good.

- rash causes/management.  The discussion starting on page 108 gives a thorough review, though overall there still seems to be no indication of who is more likely to be affected. Early intervention doesn't reduce occurrence but reduces discontinuation ( best to see your Dr. early on):

"The rash assessment and management plan specifically defined criteria for evaluating rash severity, and provided general rash management recommendations. The plan also included mandatory permanent study regimen discontinuation for Grade 3 rashes in the ongoing Phase 2 studies and additional modifications that were implemented based on Phase 2 experience.
Overall, the rash assessment and management plan had no effect on the rate of rash occurrence; however, it did have an effect on the rate of rash-related discontinuations of all treatment drugs during the Phase 3 program. In Phase 3, 1.1% of T12/PR subjects had rash- related discontinuations of all study drugs compared with 6.2% in Phase 2 (Table 40). Therefore, modifications made to the rash management plan appear to have been effective in allowing subjects to remain on treatment."

- information on prevalence of PI-resistant variants made available to patients who failed tx with tela. Nada (and Merck is no better)