So far, what's the consensus on the vx-ers who didn't clear?

[prettydamscared]

I hate to bring up a ngetive subject but wanted to clarify it in my own mind.  I was so disappointed to learn that TravelMom didn't clear, although that was probably due to the fact that she got the "dreaded" RASH at 4 days and had to discontinue the telaprevir.  She was in the 24 week study and please correct me if I'm wrong.

Chuck, (crsps,) sorry if I've butchered your screen name but you posted "yes i was the only one on this board with the vx950 who didnt clear that i know of vl start was 10 million was down to 18,000 by day 8 after that it was back up to to over 7 million in dec feb 1 million was on tripple for almost 12 weeks and soc feb 1 person on my site also didnt clear ( a group of 10 ) a couple feb 1 person on my site also didnt clear ( a group of 10 ) a couple feb 1 person on my site also didnt clear ( a group of 10 ) a couple of people were in trial never reported back at least 3 from this site. still looks to get about a 80-85% clearemce rate on tripple quite an improvement in my opinion"

It sounds like you're saying another person on your site also didn't clear.  Do you know if they were in the 12 or 24 week group.  "a couple feb 1 person on my site also didn't clear." Are you saying one or two more people from your site also didn't clear besides yourself.

We still do have PLN and APK who are clear at 4 weeks post and many more results to come in.  Can anybody thnk of anyone else?

[pln]

From what I am reading TravelMom had to stop the riba at day 4 not the vx-950? correct me if I am wrong. This is very sad news. Pam

[mremeet]

Hey guys, yeah she had to stop riba at day 4. So she completed her full 12 weeks of VX but only with IFN. And I'm pretty sure after that she continued on with IFN only, which I suppose wasn't enough to close the deal. She did clear rapidly though (UND at day 10), so it's somewhat discouraging that she rebounded with 12 full weeks of VX+IFN and then another 12 weeks of IFN. I think we were all hoping that the treatment cycle could be greatly shortened, perhaps even to 12 weeks, and also do away with ribavirin. Hopefully this isn't a sign that at least 24 weeks is required along with some level of ribavirin as well. She's only one example so it's obviously not enough of a sample size to know of course, but she did clear at day 10 and remained UND for nearly 24 weeks, so she certainly had an initial robust reponse to the drugs.

Anyway, it's sad to see. I hope she's doing ok and is recovering well from the situation. Travelmom if you're reading this hang in there, hope to hear from you soon.

Char how are you feeling? Hopefully getting along ok. And pam I guess your doing cartwheels about now huh? ;-)

[jmjm530]

That was my understand as well. As I mentioned in the related thread below, it's interesting that she stopped the ribavirin early because of the rash, while others like yourself stopped VX-950 early. The rash must have been pretty bad to stop the riba so early, so I'm assuming it was similar to the rash you and other have reported. What does seem different, however, is that the rest of you reported the onset of the rash much later in treatment.

But in any event, it seems that the severity of this rash may have as much to do with the synergy of ribavirin and Vertex alone, since she was able to continue on once the riba was eliminated.

The questions you raise regarding treating w/o riba hopefully will be answered very soon with the European trials where they are treating w/o riba in one of the arms. If they are able to succesfully treat without ribavirin -- or find a ribavirin substitute -- than maybe the rash problem will not become an issue down the road.

-- Jim

[ChrisDDD]

I certainly hope you're right and that Riba can be eliminated.  That is one nasty drug.

[TravelMom]

Thank you for all of your concern..I will list below my PCR results...but first let me explain...4 days into my treatment developed a severe rash. Lacey looking and extremely itchy..unbearable..I stopped the riba.  I attempted to restart a few times, but was unable to.  I also had to lower my Peg dose at week 10 to 135mcg, due to low neutrophil count..I then raised it again at week 13. I continued with VX-950 and INF all the way to 12 weeks and then INF alone until week 24, when I got the news...although not terribly surprised due to the discontinuation of the RIBA..

Day 1 pre dose - 2,280,000
Day 4    -    229
Day 8    -     29
Day 15   -     29
Day 22   -   < 30 UND
Day 29   -   < 30 UND
DAY 43   -     29
DAY 57   -     29
DAY 71   -     29
DAY 85   -    < 30 UND
DAY 85 POST DOSE  < 30 UND
WEEK 16  -    157
WEEK 20  -    131,000

Hope this helps.. Very disappointed, but as I mentioned because I had to stop the Riba so early on, I am not totally surprised;  

I wish you all the best, and if there is anything else I can answer for anybody, just shout.

Best Wishes,
Jodi

[jmjm530]

Thanks Jodi! I'm still puzzled on a number of levels why your doctors pulled you off the ribavirin instead of the Vertex, as SOC has an established track record while Peg and Vertex isn't even being trialed in this country. But who really knows what happened, or would have happend, if they did it the other way -- and hopefully SOC or future protocols will work better, if and when you decide to treat again.

All the best,

-- Jim

[TravelMom]

Hi Jim,

The reason I stopped the Riba and not the Vertex was because they all felt it was a "riba rash"...at the time, not many rash issues had emerged yet..the plan was to discontinue the riba, if the rash remained then we would have restarted the riba and discontinued the VX950...but since the rash subsided rather quickly, we all agreed it was the riba that caused it...I really wanted to continue with the VX-950, I knew there was a European study without Riba and was hopeful it would still work for me...oh well..gave it my best shot.

Good luck to you Jim.

[mremeet]

jim - Yeah, speaking for myself and pds I agree that the ribavirin probably played some role in the severity of our VX rash. I've been off the VX for months now, and yet I'm still struggling with a "rash residue" which is directly proportional to how much riba I take. If I take 1200mg (what I'm supposed to be on) it's just about intolerable, if I take 1000mg it's barely tolerable, and at 800mg I seem to be doing better than I have in ages (800's what I'm on now). PDS is experiencing a similar situation. So in our opinion there's little question that the riba served to exacerbate the rash, and maybe even accelerate its onset. Can't prove that, but without any question riba is a powerful irritant by itself (not to mention a red blood cell killer). So if VX (or similar analog) could help with doing away with it, then that's certainly a big step forward.

And looking at travelmom's initial viral response, it's remarkable how utterly similar it is to nearly all of our responses (accounting for obvious differences in starting VL). She cleared the virus in a very comparable timeframe as the rest of us, and did so with only 4 days of riba. Which almost suggests that someone could get by very well without the riba. But on the other hand, the sprinkling of 29's within the first 12 weeks after initially going UND suggests the riba may play a larger role than we all hope, even if a PI is being used in its stead. She's only a single patient, so again can't make broad generalizations out of what happened to her alone. But still it's a little troubling to see what appears to be a hint that PI's may not make ribavirin quite as disposable as we had all hoped. Which is a real bummer, because the stuff makes me a miserable SOB, and I know it does to most others too.

Hope you're recovering well, and I'm praying to join your exclusive SVR club by next winter sometime.

Travelmom real sorry to hear about this, I've been meaning to email you for weeks now. Everyone's been asking me about you too, so we're all really glad to hear from you again. I don't remember what your liver fibrosis was, but I seem to recall it's not too bad. Hopefully that's the case so you have plenty of time to wait out the new drugs. Hopefully they'll be able to combine telaprevir with something like schering plough's SCH503034 PI. With those two together along with peg IFN, I would think that should be enough to stomp the virus into the dirt just fine without the riba. That is, as long as the two PI's together don't cause too many skin problems (those two combined would probably just turn me into one big welt). But the point is hopefully they'll put an effective treatment strategy together sans riba without too much more time going by. In the meantime take real good care of yourself and read up on the best supplements for our livers. HR suggested NaC, lipoic acid and some others a while back. Might want to read up on it, it sounded like good advice.

Ok, hope you're hanging in there. I've been trying to mentally prepare myself for relapsing too. I know it can happen, especially to me considering what happened with the rash, early VX cessation and all the steroids I took. But all we can do is take it one day at a time. Although I have to say if I manage to take this boat all the way to 48 weeks and I end up relapsing later, that'll be one of the bitterest pills I'll ever have to swallow. So I'm really trying to get right with myself if that does in fact happen. It's got to be hard on you, I'm sorry it didn't work out. Don't be discouraged, there WILL be further developments that will help you. It's just a matter of time, so keep looking to the future.

Take care of yourself, good seeing you again.

PS>> I hope your daughter is doing well too!

[jmjm530]

You can stare at those viral load numbers till eyes are blurry and wonder what is what, so like you say we really need more numbers, especially the non-riba ARM in Europe in regards to the role of ribavirin.

For example, how come the virus hung around so long going in and out of the non-detectible range until day 85 when it seemed to clear only to come back at week 16 which would be 4 weeks after the Vertex was stopped? So was it the riba in her case or the withdrawal of the Vertex?

As to the rash, if TM's rash was caused by the riba, then how come it came on after only 4 days? Given the slower absorption of riba, the evidence seems to point more to the Vertex and yet anecdotally both you and her report the rash came on stronger with more ribavirin. In my case, for example, I also had significant skin problems but it seemed mostly interferon related.

One question. You say that TM's viral regression was similar to the rest of the groups. I assume you mean up to day 29. Did it take every then around 4 weeks to get to "<30"? For some reason I thought some of you got their earlier. Hopefully, a lot of the questions will start being answered as soon as Vertex starts releasing data which hopefully won't be too much longer. I'm guessing they are waiting for 12-week post treatment viral load numbers to be analyzed which is in a month or so.

And yeah, I'm rootin' for all of Vertexers you to meet me in SVR land in due course. I have no doubt that most of you will and pray that all of you do.

Be well,

-- Jim

[web52]

tm- im sorry it didnt work out this time. there is progress in tx & i believe there will be an effective cocktail in the near future that won't include riba. please keep us updated on your future plans, & best of luck to you. jmjm- though i cleared day 22 (had a 29 the wk before), rash didn't start right away, i think it was after 4 weeks or so. it got better several wks after discontinuing the vx. im about 160 lbs now (started at 180)& have been taking 1200 riba throughout. rash & itching controlled pretty well w/ regular use of aquaphor ointment.    

[mremeet]

You ask "...how come the virus hung around so long going in and out of the non-detectible range until day 85 when it seemed to clear only to come back at week 16 which would be 4 weeks after the Vertex was stopped? So was it the riba in her case or the withdrawal of the Vertex?"

My personal pet theory is this: I think the VX and peg together were enough to initially rapidly subdue the virus to a very low level, and keep it there while both drugs were still in play. As evidenced by the data that's clearly what happened. But obviously in her case the VX and IFN alone were not enough to eradicate the virus in only 12 weeks. Also, with all the 29's flickering on and off during the VX+IFN dosed period, it seems clear the VX has lost some of its initial umph and effectiveness. The virus seems to be holding its own at a consistent and persistent low level. It seems clear that there was a sort of low level stalemate, where viral reproduction was just matching the eradicative effects of the two drugs together. But the VX and riba were not winning the war, meanwhile the virus sits there at low levels iterating new generation after new generation (allowing it to constantly "R&D" new variants), mostly subdued but definitely hanging in there.

As you know, ordinarily when the PI's are dosed as a monotherapy, they normally have a fantastic initial decay rate, but it usually only lasts from a couple of weeks up until a month or so before a complete viral rebound back to baseline levels occurs (due to to the rapid rise of drug resistant mutants). It almost looks as if a heavily diluted version of this happened to travelmom. It appears as if the initial heft of the VX largely evaporated as treatment moved beyond a month (i.e. the typical timetable for a PI monotherapy rebound). It's as if the VX is still working on some level but isn't going in for the kill. I suspect this is because the virus is slowly evolving into a resistant form. It still has an effect on the virus, but enough mutants are surviving and replicating to resist it, and also maintain at least some resistance to IFN. But since IFN has a much more complex and multidimensional effect on the virus, it can't fully rebound in the presence of both agents. HR once called IFN a sort of combo therapy by itself due to its complex "referred action" on our immune systems (paraphrasing him here). So since the IFN's complex action cannot be easily evaded, the two drugs together were working well enough to persistently keep the virus mostly at bay, albeit not being able to go in for the kill.

Once the VX was removed, then the only action left was the IFN. The boost provided by the VX (albeit weakened over time by mutations) was no longer present and by this time the virus had been working awhile on resisting both drugs. It took it awhile to finally figure the interferon out, and obviously the IFN all by itself usually doesn't have the brute power by itself to take HCV down anyway. So I think it finally won out and broke through for good on week 16. But in my opinion, I think this would have happened anyway even with a continued course of VX (although it might have happened later than week 16). It seems clear to me that the virus was figuring the unidimensional action of the telaprevir out. The telaprevir clearly lost much of its effectiveness after the first month, apparently enough of the virus initially survived to come up with variants that could survive.

"As to the rash, if TM's rash was caused by the riba, then how come it came on after only 4 days?"

Just guessing, but to me it sounded like she simply had an allergic reaction to the ribavirin. I know it's relatively rare, but some people are allergic to it just like some folks are allergic to penicillin or peanuts or whatever. Although it took a while for the VX allergy to fully develop in myself and PDS, some people have instant allergies and react immediately upon first contact (especially with ingesting the substance). I'm learning that allergies are mysterious things, and the body's immune responses are incredibly complicated, unpredictable and certainly way over my head. But suffice to say there are all kinds of variations in how humans react to allergens. Dointime here described an early onset of a VX rash (he was only taking VX and IFN) that was quite nasty within the first 2 weeks. I thought for sure he was heading to a rash meltdown like we had, even moreso because it hit him so early. But that was not to happen, the rash subsided and he largely recovered. So it's obvious now there are all kinds of possible rash variations in time to onset, severity and even persistence. It sounds on the surface like travelmom simply was flat out allergic to riba. I don't recall, but did she say she tried it again after going off the VX? That'd be interesting to know.

"One question. You say that TM's viral regression was similar to the rest of the groups. I assume you mean up to day 29. Did it take every then around 4 weeks to get to "<30"? For some reason I thought some of you got their earlier."

Yes, her initial clearance was similar to ours (accounting for starting VL), although you're right some did clear earlier. PLN cleared (<10) at a mere 4 days, but her starting VL was only 73,000 IU/ml or so. PDS cleared at day 22 (<10) with a starting VL of 10-15 mill (don't remember exactly). I cleared at day 15 with a starting VL of 1.6 mil. I think APK's "claimed" (don't get me started! ;-) starting VL and performance were similar to this (UND at day 15 if I recall). Others were similar to this too, so travelmom's starting VL of 2.3 mil and clearing at day 22 is pretty well in line with everyone else.

Sorry to drone on, thanks for the encouragement for the SVR. I'm really hoping and praying I'll make it to the promised land. Although I'm trying to emotionally prepare myself for the worst too. I just keep reminding myself life is life, there's only so much I can control in it. Worrying about it doesn't help, so I'm trying not build my hopes up. Anyway, thanks again, hope you're making a comeback and the skin is settling down.

[jmjm530]

We should know more soon when results start getting unblinded. Don't want to get into one of those discussions, but wondering if you've thought about cutting treatment short if the official 24-week numbers look teriffic. Assuming, of course, that you're not doing well with sides, etc. I certainly would suggest anyone do any such thing but I'm sure it would be on my mind if I was treating with VX-950 presently. No answer necessary unless you want to.

Be well,

-- Jim

[jmjm530]

WHOOPS. "would" should have been "wouldn't". D*mn Freud. LOL.

[mremeet]

No it's ok to discuss. Earlier when I was much more miserable I was definitely planning on punching out, there was just no way I could continue. But now that I've reduced my riba and the resonating after effects of the VX rash seem to be dissipating, I'm feeling better. I also have Procrit now, so that will also hopefully put a spring back in my step. I plan on going the whole 48, mainly because even if the reported data is very encouraging, unfortunately it won't really directly relate to my particular scenario. I'm an oddball who experienced "the rash" which lead to the simultaneous onset of (1) an abbreviated dosage of VX, (2) riba interruptions/reductions, and (3) extensive and prolonged use of immunosuppressants. Obviously since this is the case, it would be foolhardy for me to relate the hopefully to be reported "good news" concerning high SVR rates and abbreviated courses to my situation. Unfortunately I think I need to go the distance on this crud to have a fighting chance. Although on the other hand my VL results are good, so I do have a good reason to be optimistic. So I might be able to get away with an abbreviated course, but I'll only dare to do that if I'm in itch hell by then. Thanks again, take care.

[chcnme]

So sorry to hear your story.  What a da** bummer.  I remember your name when I first came to MH (I came here reading all I could on VX), and then I always wondered how you were doing.  I can only imagine that that kind of rash is just pure maddening.   I hate to hear of anyone going through that with this treatment  (and especially not SVR on account of something that intense.)  Again, so sorry.  I hope your rash has gone away completely and that it'll never return like that again.   Maybe one day Riba will be OUT of the equation.  Keep your chin up!  

[nygirl7]

I've never even been on the vertex but still struggle pretty bad with the "rash residue" at meet calls is. I've been post tx for a month.

I can't even imagine adding in vertex on top of the riba. Together the concentration sounds as if it totally would have been unbearable.

I can see why TravelMom would have to stop the riba. It's just a damn shame.

They need a riba/ifn free treatment for us. IT's just not fair.