Aa
Telaprevir - 18 yes 0 no
Whew - that was dicey. One of the FDA advisory committee panelists was agressive in his pursuit of issues with the rash, but in the long run, he and everyone else on the panel voted to approve.
Now it goes to the FDA. Approval date (or not) is May 23. Some people are betting that the FDA will announce both BOC and TEL on May 7 - the date for Boceprevir approval (or not)
Now it goes to the FDA. Approval date (or not) is May 23. Some people are betting that the FDA will announce both BOC and TEL on May 7 - the date for Boceprevir approval (or not)
Hi Andy, its been a while since I've been around and forgot the name of the site and had to search for a while and then what was my login... crazy but I found it and you're one of the reasons why as I enjoyed greatly your posts a few years ago when things were 'dark'... we're here Telparivir is approved we're successful guinea's and others will now benefit. I wanted to say hi and will go back and read all the posts later! The Best!
Scott
Scott
Ah, so you're one of those who came before me and paved the way!! A little birdie suggested I might taste my meds so...I also tasted my TPVR tabs and could definitely tell the difference at wk 9 when I was switched to placebo. I was a little worried when I realized I was on the placebo but hey, it worked. For me the anal issues started on day 3 when I forgot to take the dose with a snack and wound up taking it on an empty stomach, OMG, rapid response in the GI tract!!! The itching was strange but the burning is what I remember. And that continued pretty much until after the 8 wk mark when the placebo replaced the TPVR. Still, all worth it. So that's another caution for future tx'ers, I think, be sure to take the med with a snack.
As others have said, thanks so much for telling your story. And good to "meet" you.
Lapis
As others have said, thanks so much for telling your story. And good to "meet" you.
Lapis
Coeric - Yes I'm the one that was tasting the pills and attempting to determine if I was on placebo or not. Actually it was three of us, and then we were also requesting other taste comparisons with other Prove 1 trial participants we met online here. Of course all of this was strictly against trial protocol rules, but desperate people will do desperate things. ;-) In the end we determined the true telaprevir pills had a very bitter, nasty metallic like taste to them. The pills dissolved very quickly and easily as soon as they were moistened with saliva. The placebos were usually described as a neutral, slightly sweetish taste. The only exception we had was one person who thought the real telaprevir pills tasted like placebos (we thought he was a Vertex plant at the time hehe). But some people have a very bland sense of taste (especially smokers, which this person was) and taste interpretations are subjective for this reason. Vertex and our trial doctors were monitoring our comments and discussion on this forum and they mentioned it us during our doctor visitations. So we kept our communications about this subject private afterwards, especially after also getting offstudy PCR's at 3 weeks to see if we were UND, which would strongly imply being on the real thing. If we were caught we might have been kicked out of the trial so we did it covertly (other than prettydamscared blurting it out here and almost blowing her cover). Anyway, seems silly now but at the time it was of paramount importance. It was a game for sure and a game I was determined to win.
willing - Thanks for the kind words, good to see you're still helping people out here. Yeah, dointime would have been helped with more riba, but as I recall her problem was caused by NO riba. She was randomized into the no riba group. Her viral decay was rapid initially, as it approached UND it started sloping off after a few weeks and then she went UND off and on for a week or two and then it came back (from my fragmented memory anyway). The antiviral kinetics for IFN and TPVR alone to me looked like a damped, prolonged version of the TPVR by itself (i.e. very rapid initial decay first 2 weeks --> 3-4 weeks approach UND asymptotically ---> float in and out of UND at low levels for a week or two--> maintain HCV+ status at low viral load thereafter. I don't recall if she got riba later, but I think she did after treating again. But by then the TPVR was useless, she had TPVR resistant strain and that ruined the whole thing. You only have one chance to get it right, although I still think dosing with another PI especially after pre-treating with IFN riba for 4 weeks prior might work well. I hope is she reads this she will comment and let me know how she’s been doing. I miss her and wish her well.
As far as my rash goes, it did get out of hand, but only because a comedy of errors ensued as a result of no prior side effect knowledge base for TPVR at that time. The one thing I hope newbies who are considering treatment consider is that although my story is awful, it's only awful because the rash was totally mismanaged. It doesn't have to be that way AT ALL for any new person considering treatment. Basically an analogy of what happened to me is the following: I wasn’t allergic to poison ivy at first. So I rolled around in poison ivy for about 5 weeks until all of a sudden - I developed an allergy to it. Then I took internal medicine (prednisone) to thwart my body’s natural reaction to this new allergy. But instead of staying clear of the poison ivy, I continued to roll around in poison ivy over and over again every day while I was taking less and less prednisone. Eventually the prednisone suppressive dose reached its critical limit (about 10mg for both me and prettydamscared), and then the bill came due for all the rolling around in poison ivy after developing (and artificially suppressing) my newfound allergy. Obviously the right thing to do is once you develop that allergy, is DUH – stay away from the poison ivy!
So again the thing that's important to remember is that the skin allergy that is developed for TPVR in the people who get it is just that - it’s DEVELOPED. It usually does not manifest itself immediately. It takes time for your body to develop an allergy to it. From what I saw the typical "time to allergy" for those susceptible to it was about 5 weeks (give or take a week). That's about what it was for me and prettydamscared and a few others I heard about through the grapevine. I did hear of rare cases of some who reacted badly to TPVR on their very first dose, but they were very rare. Most who got the bad rash only did so after about a month of treatment first.
As an aside basically this situation is similar to other skin allergies I’ve heard about. For instance, I knew a guy that used to work with epoxy resins used in custom built aircraft. He would mix these resins and use them to coat Kevlar and carbon fiber sheets wrapped around foam cores. During this work his skin was exposed to the epoxy. Even when he used gloves, he would inevitably get some on his skin. For a few years he didn’t really have a problem, but then eventually it caught up with him. He then rather suddenly developed severe rashes if he came into contact with the epoxy. From then on he no longer could come anywhere near the stuff or he would break out into hives. I’ve heard of other situations like this, where a person who had no allergy to a particular something or other, would then later develop an allergy to that same substance over time (and occasionally the reverse of this phenom could occur as well).
Also, and this is something I’ve never mentioned here before, but prettydamscared had a few VX-950 pills left after she had developed her allergy and went through her “prednisone event.” She had stopped the VX950 well before and her rash was under control, but she decided to not “waste” the few pills she had left (and it was also against trial protocol to take anymore pills, all unused meds were to be turned in). I told her not to do it, that it would cause the rash to come back with a fury. She agreed and said she wouldn’t – but she secretly did anyway. Of course the rash came back with a vengeance and she almost crashed and burned just like me. She wasn’t thinking clearly at this time and it was a big mistake. One that almost terminated her entire treatment.
Anyway, so what this means is that Telaprevir still offers a MASSIVE edge to even those people who are vulnerable to developing a bad rash like me. Knowing what I know today, I would have absolutely used TPVR if I had to do it all over again (and I was treatment naive again). Except this time I probably would have started my treatment with SOC without the TPVR first. Go maybe 2-3 weeks into treatment with the SOC and get those molecules into the system and get the immune response ramped up and clicking. Get the viral load down and my system primed. Then I would have introduced the TPVR at week 3 or 4. By that time the virus is already on the run, and knowing that I had about 5 weeks of utility from the TPVR before the itchy/scratchies set in. Stop the TPVR when the rash started up (probably around week 10 or so), continue with SOC for a total of 24 weeks and then call it quits. I think that would be pretty optimal in terms of the SVR % success rate/time of treatment/minimal side effect profile.
Specta – Hey, I’m sure boceprevir has its own place in Dantes inferno. From what I recall its main torment was “gastro issues.” I can only imagine what that means in real side effects. But Montezuma’s revenge with a garden hose up your butt comes to mind ;-) . Another little publicized (but VERY common) side effect of TPVR was “anal itching.” Out of self humility I won’t go into anymore details, but it wasn’t only my eyebrows that got scratched off. ;-)
willing - Thanks for the kind words, good to see you're still helping people out here. Yeah, dointime would have been helped with more riba, but as I recall her problem was caused by NO riba. She was randomized into the no riba group. Her viral decay was rapid initially, as it approached UND it started sloping off after a few weeks and then she went UND off and on for a week or two and then it came back (from my fragmented memory anyway). The antiviral kinetics for IFN and TPVR alone to me looked like a damped, prolonged version of the TPVR by itself (i.e. very rapid initial decay first 2 weeks --> 3-4 weeks approach UND asymptotically ---> float in and out of UND at low levels for a week or two--> maintain HCV+ status at low viral load thereafter. I don't recall if she got riba later, but I think she did after treating again. But by then the TPVR was useless, she had TPVR resistant strain and that ruined the whole thing. You only have one chance to get it right, although I still think dosing with another PI especially after pre-treating with IFN riba for 4 weeks prior might work well. I hope is she reads this she will comment and let me know how she’s been doing. I miss her and wish her well.
As far as my rash goes, it did get out of hand, but only because a comedy of errors ensued as a result of no prior side effect knowledge base for TPVR at that time. The one thing I hope newbies who are considering treatment consider is that although my story is awful, it's only awful because the rash was totally mismanaged. It doesn't have to be that way AT ALL for any new person considering treatment. Basically an analogy of what happened to me is the following: I wasn’t allergic to poison ivy at first. So I rolled around in poison ivy for about 5 weeks until all of a sudden - I developed an allergy to it. Then I took internal medicine (prednisone) to thwart my body’s natural reaction to this new allergy. But instead of staying clear of the poison ivy, I continued to roll around in poison ivy over and over again every day while I was taking less and less prednisone. Eventually the prednisone suppressive dose reached its critical limit (about 10mg for both me and prettydamscared), and then the bill came due for all the rolling around in poison ivy after developing (and artificially suppressing) my newfound allergy. Obviously the right thing to do is once you develop that allergy, is DUH – stay away from the poison ivy!
So again the thing that's important to remember is that the skin allergy that is developed for TPVR in the people who get it is just that - it’s DEVELOPED. It usually does not manifest itself immediately. It takes time for your body to develop an allergy to it. From what I saw the typical "time to allergy" for those susceptible to it was about 5 weeks (give or take a week). That's about what it was for me and prettydamscared and a few others I heard about through the grapevine. I did hear of rare cases of some who reacted badly to TPVR on their very first dose, but they were very rare. Most who got the bad rash only did so after about a month of treatment first.
As an aside basically this situation is similar to other skin allergies I’ve heard about. For instance, I knew a guy that used to work with epoxy resins used in custom built aircraft. He would mix these resins and use them to coat Kevlar and carbon fiber sheets wrapped around foam cores. During this work his skin was exposed to the epoxy. Even when he used gloves, he would inevitably get some on his skin. For a few years he didn’t really have a problem, but then eventually it caught up with him. He then rather suddenly developed severe rashes if he came into contact with the epoxy. From then on he no longer could come anywhere near the stuff or he would break out into hives. I’ve heard of other situations like this, where a person who had no allergy to a particular something or other, would then later develop an allergy to that same substance over time (and occasionally the reverse of this phenom could occur as well).
Also, and this is something I’ve never mentioned here before, but prettydamscared had a few VX-950 pills left after she had developed her allergy and went through her “prednisone event.” She had stopped the VX950 well before and her rash was under control, but she decided to not “waste” the few pills she had left (and it was also against trial protocol to take anymore pills, all unused meds were to be turned in). I told her not to do it, that it would cause the rash to come back with a fury. She agreed and said she wouldn’t – but she secretly did anyway. Of course the rash came back with a vengeance and she almost crashed and burned just like me. She wasn’t thinking clearly at this time and it was a big mistake. One that almost terminated her entire treatment.
Anyway, so what this means is that Telaprevir still offers a MASSIVE edge to even those people who are vulnerable to developing a bad rash like me. Knowing what I know today, I would have absolutely used TPVR if I had to do it all over again (and I was treatment naive again). Except this time I probably would have started my treatment with SOC without the TPVR first. Go maybe 2-3 weeks into treatment with the SOC and get those molecules into the system and get the immune response ramped up and clicking. Get the viral load down and my system primed. Then I would have introduced the TPVR at week 3 or 4. By that time the virus is already on the run, and knowing that I had about 5 weeks of utility from the TPVR before the itchy/scratchies set in. Stop the TPVR when the rash started up (probably around week 10 or so), continue with SOC for a total of 24 weeks and then call it quits. I think that would be pretty optimal in terms of the SVR % success rate/time of treatment/minimal side effect profile.
Specta – Hey, I’m sure boceprevir has its own place in Dantes inferno. From what I recall its main torment was “gastro issues.” I can only imagine what that means in real side effects. But Montezuma’s revenge with a garden hose up your butt comes to mind ;-) . Another little publicized (but VERY common) side effect of TPVR was “anal itching.” Out of self humility I won’t go into anymore details, but it wasn’t only my eyebrows that got scratched off. ;-)
Thank you for your extremely well written and vivid post. I felt like I was scratching my eyebrows off with you as I read!
Congrats on your SVR and incredible perseverance. It reminds me that I had little to complain about in comparison, although my boceprevir experience was no bed of roses.
Take Care,
Dave
Congrats on your SVR and incredible perseverance. It reminds me that I had little to complain about in comparison, although my boceprevir experience was no bed of roses.
Take Care,
Dave
This is an interesting read and as happens....so many points end up getting made that it becomes difficult to respond to them all, but a few things that come to mind.....
Re the "rash", it could be that Vertex was able to slightly improve their rash management program, or their understanding of it.
There could be some genetic markers or predispositions for it. (but I've read nothing yet)
Improved Rash management programs lowered the drop out rate, thus increasing SVR.
I theorize that increasing lead in time could also increase the incidents of rash. As it sits some people may start and finish the 12 week triple therapy phase and cease TVR. Adding another 4 weeks of TVR could also increase the incidence of rashes.
------------------------------------
When i was in a trial, for all of a week before I dropped out w/o dosing it seemed to me that one of the objective of a trial is to gather data. Maybe ya'll can figure that some doctors want to "cure" people and therefore select the ones they figure have the best chance. Others might suggest that some doctors may select the sick ones who really need the help; those damaged the most. One thing i might add to the mix is that the drug pipeline is also a money & information pipeline for those who run the trials. What they are really doing is mining data. I feel that one of the objectives is to select those people who are most likely to start and stay on the trial. The people running the trial probably have a long checklist of objectives.... a punch list of duties, labs, doses, stats they must acquire from each patient. Each one of these also triggers a payment to the doctor/clinic.
I don't mean to suggest that it's all about money, since I think that they are doing tremendous work, groundbreaking work. I just think that if given the choice of them in effect betting on a finisher, they will tend to select those who will go for the full ride.
If I recall there were several early TVR trial participants that dropped out early; one after only one dose. It messes up the numbers, looks bad and then they have to start all over, which is more work for them. The numbers cut both ways in this subject; dropouts had the connotation of being failures. In reality, many of the dropouts attained an SVR. Just like Trish's drug trial; tell any of the people who SVR'ed that their drug failed. My point is that numbers can only tell so much of the story....
RE willing; I think you may have a point about muddy stats, but when you put it in the context of other trials, look at all the pegasys and pegintron studies, my God.... they are still looking and finding superiorities over one another. There is a large amount of statistical obfuscation which occurs, in trial design, in running the trials and in the *presentation* of the numbers. Over all, Vertex ran very clean trials and without other rescue drugs that served to inflate their response and SVR rate. Further, they have very inclusive trials and if memory serves held one of the more definitive null responder trials to achieve better data on that subject; more so than their competitor.
Also..... not fair or objective clamoring about the other timing of trials for HIV/coinfection. I believe it is the standard order that such studies are held. These type trials are done at the end near approval, not on the front end of trials. FWIW they were doing trials in 2008 which laid groundwork the trials in question;
http://clinicaltrials.gov/ct2/show/NCT00775125?term=telaprevir%2C+HIV&rank=5
Looks to me as though some of the resistance issues may even be nearly mute. Have there not been studies which have shown that the mutation resistant variants revert back to wild type after about 2 years? IE; if 100 people treat, 70% SVR you may be left with 30 people w/ resistant variants. After 2 years these same people may no longer have those resistant variants and may try again, or try with some other additional adjunct ( a lead in, an add on like alinia or a new protease/polymerase inhibitor, quad therapy etc.
I'm not sure that you can make the case that these 30 people who initially fail out of the running for SVR. It looks to me as though it is still an acceptable gamble.
best,
Willy
Re the "rash", it could be that Vertex was able to slightly improve their rash management program, or their understanding of it.
There could be some genetic markers or predispositions for it. (but I've read nothing yet)
Improved Rash management programs lowered the drop out rate, thus increasing SVR.
I theorize that increasing lead in time could also increase the incidents of rash. As it sits some people may start and finish the 12 week triple therapy phase and cease TVR. Adding another 4 weeks of TVR could also increase the incidence of rashes.
------------------------------------
When i was in a trial, for all of a week before I dropped out w/o dosing it seemed to me that one of the objective of a trial is to gather data. Maybe ya'll can figure that some doctors want to "cure" people and therefore select the ones they figure have the best chance. Others might suggest that some doctors may select the sick ones who really need the help; those damaged the most. One thing i might add to the mix is that the drug pipeline is also a money & information pipeline for those who run the trials. What they are really doing is mining data. I feel that one of the objectives is to select those people who are most likely to start and stay on the trial. The people running the trial probably have a long checklist of objectives.... a punch list of duties, labs, doses, stats they must acquire from each patient. Each one of these also triggers a payment to the doctor/clinic.
I don't mean to suggest that it's all about money, since I think that they are doing tremendous work, groundbreaking work. I just think that if given the choice of them in effect betting on a finisher, they will tend to select those who will go for the full ride.
If I recall there were several early TVR trial participants that dropped out early; one after only one dose. It messes up the numbers, looks bad and then they have to start all over, which is more work for them. The numbers cut both ways in this subject; dropouts had the connotation of being failures. In reality, many of the dropouts attained an SVR. Just like Trish's drug trial; tell any of the people who SVR'ed that their drug failed. My point is that numbers can only tell so much of the story....
RE willing; I think you may have a point about muddy stats, but when you put it in the context of other trials, look at all the pegasys and pegintron studies, my God.... they are still looking and finding superiorities over one another. There is a large amount of statistical obfuscation which occurs, in trial design, in running the trials and in the *presentation* of the numbers. Over all, Vertex ran very clean trials and without other rescue drugs that served to inflate their response and SVR rate. Further, they have very inclusive trials and if memory serves held one of the more definitive null responder trials to achieve better data on that subject; more so than their competitor.
Also..... not fair or objective clamoring about the other timing of trials for HIV/coinfection. I believe it is the standard order that such studies are held. These type trials are done at the end near approval, not on the front end of trials. FWIW they were doing trials in 2008 which laid groundwork the trials in question;
http://clinicaltrials.gov/ct2/show/NCT00775125?term=telaprevir%2C+HIV&rank=5
Looks to me as though some of the resistance issues may even be nearly mute. Have there not been studies which have shown that the mutation resistant variants revert back to wild type after about 2 years? IE; if 100 people treat, 70% SVR you may be left with 30 people w/ resistant variants. After 2 years these same people may no longer have those resistant variants and may try again, or try with some other additional adjunct ( a lead in, an add on like alinia or a new protease/polymerase inhibitor, quad therapy etc.
I'm not sure that you can make the case that these 30 people who initially fail out of the running for SVR. It looks to me as though it is still an acceptable gamble.
best,
Willy
thanks for a great and vivid summary - the description of the crowd parting as you approached the emergency room desk makes an impression! After that ordeal I'm sure glad it worked for you - would you consider tela again if it hadn't? Per her post above, josiejo also required hospitalization but got no svr at the end. Similarly for dointime, more riba may well have made a difference in tx outcome but would not have made the rash any easier to handle.
One option that will be available after approval will be to switch to boce if the rash proves excessive thus avoiding any decrease in PI pressure on the virus. From your description it sounds as if things can get out of hand pretty fast - so for the transition to work smoothly a patient would have to do some prior planning.
One option that will be available after approval will be to switch to boce if the rash proves excessive thus avoiding any decrease in PI pressure on the virus. From your description it sounds as if things can get out of hand pretty fast - so for the transition to work smoothly a patient would have to do some prior planning.
mremeet - definitely a hero's journey if i ever heard one. i've seen folks bouncing off walls on big doses of prednisone, but not on top of three hcv tx drugs! thank you for coming back and sharing. i recall a story about someone tasting the tela pill in order to insure they were getting the real thing - wondering if that was you?
andiamo1 - part of my interest in a lead-in is sort of like sticking my toe in the pool to check the water temp before i jump in. let's see how this naive responds to interferon/riba before jumping into the deep end with the PI. i appreciate your advice to jump into the deep end and get on with it. certainly enduring any more time with interferon and riba on board does not make much sense. i know that in order to replicate the trials i would need to stick to the 24 weeks of 48 weeks after adding the PI.
willing - interesting that only 38% on the placebo went to SVR in the sprint2 trials. makes me wonder if these trials can be compared strictly on the numbers. your point to concentrate on confidence intervals is well taken. thanks so much for the links. i will definitely take a closer look at the briefing docs.
thanks everyone
eric
andiamo1 - part of my interest in a lead-in is sort of like sticking my toe in the pool to check the water temp before i jump in. let's see how this naive responds to interferon/riba before jumping into the deep end with the PI. i appreciate your advice to jump into the deep end and get on with it. certainly enduring any more time with interferon and riba on board does not make much sense. i know that in order to replicate the trials i would need to stick to the 24 weeks of 48 weeks after adding the PI.
willing - interesting that only 38% on the placebo went to SVR in the sprint2 trials. makes me wonder if these trials can be compared strictly on the numbers. your point to concentrate on confidence intervals is well taken. thanks so much for the links. i will definitely take a closer look at the briefing docs.
thanks everyone
eric
Great to see you back. I am here intermittently, but this time got involved in some heated discussions about Vertex. I do agree with what you said.
Thanks for the kind words nygirl and mike. I deeply depended on this place during my treatment and everyone here helped me learn and get through my treatment. That's what this place is all about, and thank god it was here to help me through. And it's not always easy for everyone to get along while being on these drugs and going through these side effects. Basically I entered into a period of temporary insanity and I got so wrapped up into my own world and my desperate attempt to kill this farking virus once and for all. Anyway, apologies for any harsh words said in the past. The whole experience seems like a long ago dark dream already. I hope more and more people get treated successfully and come out on the other side like we all did.
Andiamo when you say "The standard thinking is that the combo of interferon and ribaviron will exacerbate any skin problems." I believe this is generally true, except I would change the "will" in your statement to a "may." Of course it is a general statement and it will not apply to everyone, but generally I believe it is true. On the upside, I think if Tx does exacerbate an existing condition during treatment, it usually will not leave a lasting effect after treatment ends. One thing's for sure, IFN, Ribavirin and Telaprevir are all powerful drugs and they can make your body do bad things, especially in regards to your skin.
And Javi you ask about the solumedrol. I'm not a doctor, but to my knowledge solumedrol is a drug that is only used in rather extreme circumstances when no other choice exists. Like in the situation I was in or if memory serves Mike Simon also received it to deal with organ rejection issues pertaining to his liver transplant (correct me if I'm wrong mike). As previously stated, prednisone and solumedrol are immunosuppressants. Immunosuppressants, as its name implies, suppresses your immune system and if not used judiciously they can make you vulnerable to infections and other serious health problems. And you also do not want to take them during treatment because the whole point of treatment is to boost your immune system into overdrive for the purpose of driving the virus from your body once and for all. Taking solumedrol and prednisone will counteract the immune system boosting effects of IFN and possibly ribavirin, which are essential for achieving SVR. Good luck with your treatment.
Andiamo when you say "The standard thinking is that the combo of interferon and ribaviron will exacerbate any skin problems." I believe this is generally true, except I would change the "will" in your statement to a "may." Of course it is a general statement and it will not apply to everyone, but generally I believe it is true. On the upside, I think if Tx does exacerbate an existing condition during treatment, it usually will not leave a lasting effect after treatment ends. One thing's for sure, IFN, Ribavirin and Telaprevir are all powerful drugs and they can make your body do bad things, especially in regards to your skin.
And Javi you ask about the solumedrol. I'm not a doctor, but to my knowledge solumedrol is a drug that is only used in rather extreme circumstances when no other choice exists. Like in the situation I was in or if memory serves Mike Simon also received it to deal with organ rejection issues pertaining to his liver transplant (correct me if I'm wrong mike). As previously stated, prednisone and solumedrol are immunosuppressants. Immunosuppressants, as its name implies, suppresses your immune system and if not used judiciously they can make you vulnerable to infections and other serious health problems. And you also do not want to take them during treatment because the whole point of treatment is to boost your immune system into overdrive for the purpose of driving the virus from your body once and for all. Taking solumedrol and prednisone will counteract the immune system boosting effects of IFN and possibly ribavirin, which are essential for achieving SVR. Good luck with your treatment.
I can only describe my own experience. I never had psoriasis before I treated with interferon. After I completed my next to last treatment, I developed a mild case of it. When I started my last treatment, it disappeared! After I stopped, it came back once again.
My conclusion from this is that no one has a clue what psoriasis and interferon have in common. Some people thought it might be a predictor of a Telaprevir rash, but I didn't get the rash. The standard thinking is that the combo of interferon and ribaviron will exacerbate any skin problems. That was not my experience.
My conclusion from this is that no one has a clue what psoriasis and interferon have in common. Some people thought it might be a predictor of a Telaprevir rash, but I didn't get the rash. The standard thinking is that the combo of interferon and ribaviron will exacerbate any skin problems. That was not my experience.
wow great story!!! I am scared for treatment because I have bad psoraisis and not sure how that is going to do on treatment, due to the immune boost I will recieve may cause psoraisis to flare and go crazy! anyone experience this? and I wonder if solu-medroli will help with this? I know prednisone is a drug they prescribe for psoraisis
That's a great story.
You fought and won one very hard battle.
Solu-Medroll is one serious drug - yes indeed.
Be well,
Mike
You fought and won one very hard battle.
Solu-Medroll is one serious drug - yes indeed.
Be well,
Mike
Wow meet I had forgotten all about all that (and prettydamscared). It's no wonder we all care about each other so much we have been through more than anyone could understand had they not gone through it with their internet support group.
Man I really just almost cried.
Man I really just almost cried.
cont...Anyway, long story short, I limped along after that for a total of about 40 weeks of tx. I missed 1 IFN shot during the rash fiasco and my riba dose was cut back from 1600mg/day (I think?) to about 800-1000 daily. I could only tolerate about 800mg of riba a day towards the end because it irritated my skin so bad. Although the major rash was gone, my skin was still very sensitive and remained so until the end of treatment. I literally scratched the eyebrows off my face I itched so bad, but yet I had these freakishly long eyebrows. I looked like a Dr Suess character. Well, sort of a cross between Dr Phibes and a Dr Suess character. ;-)
But guess what? I would go on to be cured. And looking back on it, now with 20/20 hindsight the Telaprevir was a critical hingepin in my successful treatment. It worked, no doubt about it. Any thoughtful and reasonably well informed doctor prescribing Telaprevir+IFN+riba nowadays (as opposed to the summer of 2006) should now know about the typical rash profile that occurs in those unfortunate enough to get the PI rash. The solution to it is to simply stop the drug once it gets going. Simple as that - identify it properly and stop it. Telaprevir works it magic over a relatively short period of time. Usually it does what it's going to do within about a month. The IFN and riba do the rest and they require a longer period of time to finish the job. But the point is that they can finish the job without the Telaprevir. That is, after it has decimated the virus to the extent that only a mopping up of stragglers is required in the final portion of the thankfully abbreviated treatment. Telaprevir offers tremendous utility, even in those that get the rash. As long as you can tolerate it for a few weeks, it can greatly help those people too (as it did me). You just take it as long as you can, and simply stop the drug when you have to and continue on with the other two drugs. With what we know today there's absolutely no need for anyone to go through what I did and others (namely "prettydamscared").
In fact, I've come to believe that in my case I was actually SVR by week 7. Of course there's no way for me to know for certain, but I know I was UND by week 2 and less than 2 IU/ml by week 3. I also had a robust reaction to the IFN and ribavirin with a very nasty flu-like reaction to my first shot (indicating a healthy physiological response). I believe the telaprevir in conjunction with the other drugs did the virus in in a way that made my (1) early discontinuance to the Telaprevir, (2) prolonged exposures to prednisone and solumedrol and (3) my reduced riba dosages afterwards - irrelevant after week 7. And I know from some of the concurrent UK Prove 1 study participants (dointime etc) that there was a young woman who crashed and burned with a PI rash about the same time I did into treatment. Except she bailed and discontinued early, but yet she SVR'ed anyway. I know there have been others who match this profile as well.
Lastly, someone mentioned dointime and some others above. Dointime failed treatment but it wasn't because she burned out on the rash. She did get a rash, and she did suffer from it. But the main reason she failed tx is because she was not receiving ribavirin. At the time it was not known if ribavirin was an essential element of IFN+Telaprevir therapy. We now know that it is. Several others also failed for this reason, unfortunately. Also, prettydamscared was in the same trial I was in and we treated together with the same doctor. We both experienced the rash and were treated with prednisone as described previously. Except she didn't take the solumedrol like I did. She made it to about week 40 like I did and appeared to be well on her way to SVR-ing, but unfortunately was killed in a car accident about 3 months post tx.
Anyway, my vote is definitely in favor of Telaprevir. If it can work for me, it can work for almost anyone. You just gotta know how to use it and very carefully monitor how things are going as you move through those most critical early weeks of tx.
But guess what? I would go on to be cured. And looking back on it, now with 20/20 hindsight the Telaprevir was a critical hingepin in my successful treatment. It worked, no doubt about it. Any thoughtful and reasonably well informed doctor prescribing Telaprevir+IFN+riba nowadays (as opposed to the summer of 2006) should now know about the typical rash profile that occurs in those unfortunate enough to get the PI rash. The solution to it is to simply stop the drug once it gets going. Simple as that - identify it properly and stop it. Telaprevir works it magic over a relatively short period of time. Usually it does what it's going to do within about a month. The IFN and riba do the rest and they require a longer period of time to finish the job. But the point is that they can finish the job without the Telaprevir. That is, after it has decimated the virus to the extent that only a mopping up of stragglers is required in the final portion of the thankfully abbreviated treatment. Telaprevir offers tremendous utility, even in those that get the rash. As long as you can tolerate it for a few weeks, it can greatly help those people too (as it did me). You just take it as long as you can, and simply stop the drug when you have to and continue on with the other two drugs. With what we know today there's absolutely no need for anyone to go through what I did and others (namely "prettydamscared").
In fact, I've come to believe that in my case I was actually SVR by week 7. Of course there's no way for me to know for certain, but I know I was UND by week 2 and less than 2 IU/ml by week 3. I also had a robust reaction to the IFN and ribavirin with a very nasty flu-like reaction to my first shot (indicating a healthy physiological response). I believe the telaprevir in conjunction with the other drugs did the virus in in a way that made my (1) early discontinuance to the Telaprevir, (2) prolonged exposures to prednisone and solumedrol and (3) my reduced riba dosages afterwards - irrelevant after week 7. And I know from some of the concurrent UK Prove 1 study participants (dointime etc) that there was a young woman who crashed and burned with a PI rash about the same time I did into treatment. Except she bailed and discontinued early, but yet she SVR'ed anyway. I know there have been others who match this profile as well.
Lastly, someone mentioned dointime and some others above. Dointime failed treatment but it wasn't because she burned out on the rash. She did get a rash, and she did suffer from it. But the main reason she failed tx is because she was not receiving ribavirin. At the time it was not known if ribavirin was an essential element of IFN+Telaprevir therapy. We now know that it is. Several others also failed for this reason, unfortunately. Also, prettydamscared was in the same trial I was in and we treated together with the same doctor. We both experienced the rash and were treated with prednisone as described previously. Except she didn't take the solumedrol like I did. She made it to about week 40 like I did and appeared to be well on her way to SVR-ing, but unfortunately was killed in a car accident about 3 months post tx.
Anyway, my vote is definitely in favor of Telaprevir. If it can work for me, it can work for almost anyone. You just gotta know how to use it and very carefully monitor how things are going as you move through those most critical early weeks of tx.
I'm really happy to see that Telaprevir (formerly VX-950) is successfully making its way through the approval process and appears to be finally coming to market; it's long overdue in my opinion.
As a brief introduction for those who don't know me, I was in the Prove 1 trial which was the first full length triple therapy Telaprevir trial conducted (starting in summer of 2006). I received Telaprevir (I was not in placebo group) along with riba and IFN. Initially I started off in the trial without any undue side effects, other than a nasty flu like reaction to the first IFN shot (which is fairly common and cleared up by the 2nd shot). I was doing ok until about week 6 or so (it's been awhile, so my dates might be a bit off). That's when I started to get a peculiar rash that seemed to grow in intensity over several days. At first it wasn't clear what it was because there was no background data or experience to pull from. And since both IFN and riba can also cause rather severe rashes (either individually or in tandem) in some people, it wasn't clear the Telaprevir was the offending agent to either me or my doctor.
I tried to deal with the rash through week 6, but it just got worse and worse. It appeared as if it was going to derail my treatment which was an extremely depressing and upsetting thing at the time. My doctor just kept telling me to hang in there and let’s see what happens etc (again, mostly due to plain ignorance about the unknown side effect profile of Telaprevir at the time). By week 7 it was too much and something had to be done, including the possibility of discontinuance. I went to see the doctor and he reluctantly prescribed prednisone, which is an oral immunosuppressant. Immunosuppressants are essentially the opposite of immunostimulants and normally you would never want to take both at the same time. Interferon (and perhaps ribavirin) are immunostimulants, and normally you would never want to take a drug that would counteract their effects in any way during HCV treatment. Doing so could easily result in treatment failure, especially for the already hard to treat geno 1 patients. At the time I knew this and really didn't want to take prednisone, but due to the severity of the rash, I had no choice.
Prednisone is commonly used to stop nasty allergic reactions (which may be caused by all manner of things) and is also used to help prevent organ rejection in transplant patients. It's powerful medicine and it can have very bad side effects if overused (or misused). But the prednisone was a magic bullet to my rash at the time. My red, bumpy, itchy rash evaporated within hours of taking the medicine at first. It worked great and it appeared I was back on track with the trial, although with more bridges to cross in the weeks to come.
When prednisone is prescribed to address an allergic reaction of any type, usually two things happen. First is that the offending allergen and mode of exposure is identified and eliminated. Secondly, prednisone is initiated at a relatively high dose initially; I believe for me it started out at about 40 mg daily. Then the dose is tapered off over about 2 weeks by gradually lowering the dosage received as the days tick by. The reason this is done is because if you suddenly chop prednisone dosage off to zero overnight, your body can experience a severe allergic relapse in response to the abrupt change in internal body chemistry - even in the absence of the original allergen (I forget the exact mechanism but I think it might have something to do with histamines etc).
So after my initial positive reaction to prednisone, I began tapering down as the days went by. I also continued on full triple therapy which included the full dosage of telaprevir. Unbeknownst to me and my doctor at the time, I was one of the unlucky ones that had developed a severe allergy to telaprevir after about 5 weeks of exposure. The prednisone was successfully thwarting my allergic reaction to the drug as long as the dosage was high enough. But once my prednisone dose tapered off to about 5-10 mg daily, my body started once again to react to the telaprevir, except this time it was *different*.
Basically the rash exploded back into full flower at the lower prednisone dose, except this time it appeared much more ferocious. It was frightening how aggressive it grew and spread. My doctor told me to stop the Telaprevir, which I did promptly out of sheer fear of what was happening. He also told me to jack the prednisone dose back up to the original starting dose of 40mg, which I did. But this time, nuthin' doin. The rash would not go away, even several days after stopping the Telaprevir. So my prednisone dose was increased more and more, until basically I was eating it like candy. I maxed out at about 80mg a day, but the rash STILL wouldn't go away. I was getting terrified and sleep deprived and delirious (with daily rantings here on this forum lol) and my doctor was helpless to come up with any more answers on how to deal with it other than also stopping the IFN and riba as well. But I didn't want to do that, I wanted to finish off the virus and since I was only 7-8 weeks into treatment by this time I didn’t want to risk stopping and come out of it relapsing with a PI resistant strain (I knew I was UND at 3 weeks because I had a 2 IU/ml > PCR done "offstudy"). So as a last ditch effort I went to the emergency room with my leprosy face and body. All the people at the front desk gave way immediately as I walked forward, fearing I was going to give them whatever crud I had. It was pretty hilarious actually.
So the emergency room administered an IV drug called solumedrol, which again is a powerful immunosuppressant usually given to patients experiencing life threatening allergic reactions to bee stings, poison ivy etc. If you've ever seen those old Lon Chaney werewolf movies with the time lapse photography where his face is transformed from his werewolf form back into his normal self, then you know what happened to me. Because that's exactly what happened to my skin once that solumedrol flowed into my veins. You could literally see the red color draining from my rash as the drug took effect in just minutes. You could actually see the raised bumps start to flatten out, and within 15 minutes I was a new man, albeit completely drained from the whole ordeal. It wasn't an ideal situation at all because the solumedrol was very powerfully suppressing my immune system and weakening the effects of the IFN and riba to the extreme. I dreaded the thought that the virus was getting a foothold in my body again just as it was probably tottering on the brink of extinction. But it had to be done and I would just have to take my lumps in terms of risking a lost SVR. cont...
As a brief introduction for those who don't know me, I was in the Prove 1 trial which was the first full length triple therapy Telaprevir trial conducted (starting in summer of 2006). I received Telaprevir (I was not in placebo group) along with riba and IFN. Initially I started off in the trial without any undue side effects, other than a nasty flu like reaction to the first IFN shot (which is fairly common and cleared up by the 2nd shot). I was doing ok until about week 6 or so (it's been awhile, so my dates might be a bit off). That's when I started to get a peculiar rash that seemed to grow in intensity over several days. At first it wasn't clear what it was because there was no background data or experience to pull from. And since both IFN and riba can also cause rather severe rashes (either individually or in tandem) in some people, it wasn't clear the Telaprevir was the offending agent to either me or my doctor.
I tried to deal with the rash through week 6, but it just got worse and worse. It appeared as if it was going to derail my treatment which was an extremely depressing and upsetting thing at the time. My doctor just kept telling me to hang in there and let’s see what happens etc (again, mostly due to plain ignorance about the unknown side effect profile of Telaprevir at the time). By week 7 it was too much and something had to be done, including the possibility of discontinuance. I went to see the doctor and he reluctantly prescribed prednisone, which is an oral immunosuppressant. Immunosuppressants are essentially the opposite of immunostimulants and normally you would never want to take both at the same time. Interferon (and perhaps ribavirin) are immunostimulants, and normally you would never want to take a drug that would counteract their effects in any way during HCV treatment. Doing so could easily result in treatment failure, especially for the already hard to treat geno 1 patients. At the time I knew this and really didn't want to take prednisone, but due to the severity of the rash, I had no choice.
Prednisone is commonly used to stop nasty allergic reactions (which may be caused by all manner of things) and is also used to help prevent organ rejection in transplant patients. It's powerful medicine and it can have very bad side effects if overused (or misused). But the prednisone was a magic bullet to my rash at the time. My red, bumpy, itchy rash evaporated within hours of taking the medicine at first. It worked great and it appeared I was back on track with the trial, although with more bridges to cross in the weeks to come.
When prednisone is prescribed to address an allergic reaction of any type, usually two things happen. First is that the offending allergen and mode of exposure is identified and eliminated. Secondly, prednisone is initiated at a relatively high dose initially; I believe for me it started out at about 40 mg daily. Then the dose is tapered off over about 2 weeks by gradually lowering the dosage received as the days tick by. The reason this is done is because if you suddenly chop prednisone dosage off to zero overnight, your body can experience a severe allergic relapse in response to the abrupt change in internal body chemistry - even in the absence of the original allergen (I forget the exact mechanism but I think it might have something to do with histamines etc).
So after my initial positive reaction to prednisone, I began tapering down as the days went by. I also continued on full triple therapy which included the full dosage of telaprevir. Unbeknownst to me and my doctor at the time, I was one of the unlucky ones that had developed a severe allergy to telaprevir after about 5 weeks of exposure. The prednisone was successfully thwarting my allergic reaction to the drug as long as the dosage was high enough. But once my prednisone dose tapered off to about 5-10 mg daily, my body started once again to react to the telaprevir, except this time it was *different*.
Basically the rash exploded back into full flower at the lower prednisone dose, except this time it appeared much more ferocious. It was frightening how aggressive it grew and spread. My doctor told me to stop the Telaprevir, which I did promptly out of sheer fear of what was happening. He also told me to jack the prednisone dose back up to the original starting dose of 40mg, which I did. But this time, nuthin' doin. The rash would not go away, even several days after stopping the Telaprevir. So my prednisone dose was increased more and more, until basically I was eating it like candy. I maxed out at about 80mg a day, but the rash STILL wouldn't go away. I was getting terrified and sleep deprived and delirious (with daily rantings here on this forum lol) and my doctor was helpless to come up with any more answers on how to deal with it other than also stopping the IFN and riba as well. But I didn't want to do that, I wanted to finish off the virus and since I was only 7-8 weeks into treatment by this time I didn’t want to risk stopping and come out of it relapsing with a PI resistant strain (I knew I was UND at 3 weeks because I had a 2 IU/ml > PCR done "offstudy"). So as a last ditch effort I went to the emergency room with my leprosy face and body. All the people at the front desk gave way immediately as I walked forward, fearing I was going to give them whatever crud I had. It was pretty hilarious actually.
So the emergency room administered an IV drug called solumedrol, which again is a powerful immunosuppressant usually given to patients experiencing life threatening allergic reactions to bee stings, poison ivy etc. If you've ever seen those old Lon Chaney werewolf movies with the time lapse photography where his face is transformed from his werewolf form back into his normal self, then you know what happened to me. Because that's exactly what happened to my skin once that solumedrol flowed into my veins. You could literally see the red color draining from my rash as the drug took effect in just minutes. You could actually see the raised bumps start to flatten out, and within 15 minutes I was a new man, albeit completely drained from the whole ordeal. It wasn't an ideal situation at all because the solumedrol was very powerfully suppressing my immune system and weakening the effects of the IFN and riba to the extreme. I dreaded the thought that the virus was getting a foothold in my body again just as it was probably tottering on the brink of extinction. But it had to be done and I would just have to take my lumps in terms of risking a lost SVR. cont...
"How likely is an 8% difference to arise by chance alone in samples of that size if there were really no difference in patient screening? "
Possibly likely depending on the standard deviation. This is a small selection out of a large group. 40% has been the published number for many years for SOC, so I would assume their number is quite accurate.
If you look at all the published SOC SVR rates, they seem to be in the 40 - 48% range and have been for many years.
Possibly likely depending on the standard deviation. This is a small selection out of a large group. 40% has been the published number for many years for SOC, so I would assume their number is quite accurate.
If you look at all the published SOC SVR rates, they seem to be in the 40 - 48% range and have been for many years.
>That would have been evident after the Prove 3 trial, not before
agreed - but I believe it also suggests your positive experience with tela may not be accessible to someone who goes into triple tx as a prior null, not as a relapser
>isn't there a slightly different formula where you need to subtract 1 from the denominator?.
yes, but that shows up in estimating the standard deviation of a continuous variable eg
http://en.wikipedia.org/wiki/Standard_deviation
which would be applicable if comparing a measurement like say HgB decline. However in comparing SVR rates the distribution is a discrete one with an outcome like a coin flip so the formulas differ. A description, including worked example, is here
http://www.stat.yale.edu/Courses/1997-98/101/catinf.htm
at the label "Comparison of two proportions".
Confidence intervals can shed some additional light on comparison because they incorporate the noise expected in estimates made from samples of a given size.
For example did Vertex's patient selection procedure for Advance result in an easier-to-treat sample than in Merck's equivalent Sprint-2 study? Different SVR rates in the randomly assigned placebo arms would show this effect. For Advance, 361 pts were assigned placebo and 166 reached SVR( 46%). In Sprint-2 363 pts were assigned placebo and only 137 reached SVR (38%). How likely is an 8% difference to arise by chance alone in samples of that size if there were really no difference in patient screening?
Applying the equation from that Yale stat page above gives a 95% confidence interval of (0.01, 0.154) Interestingly the CI does not include zero suggesting that for samples that large an 8% difference is unlikely by chance alone - but the lower bound is close to zero (they cheated, but only a little bit?)
The same approach could be used to sort out whether the difference in SVR rates among naives between tela and boce could easily have arisen by chance or suggests separate underlying distributions (haven't done this).
agreed - but I believe it also suggests your positive experience with tela may not be accessible to someone who goes into triple tx as a prior null, not as a relapser
>isn't there a slightly different formula where you need to subtract 1 from the denominator?.
yes, but that shows up in estimating the standard deviation of a continuous variable eg
http://en.wikipedia.org/wiki/Standard_deviation
which would be applicable if comparing a measurement like say HgB decline. However in comparing SVR rates the distribution is a discrete one with an outcome like a coin flip so the formulas differ. A description, including worked example, is here
http://www.stat.yale.edu/Courses/1997-98/101/catinf.htm
at the label "Comparison of two proportions".
Confidence intervals can shed some additional light on comparison because they incorporate the noise expected in estimates made from samples of a given size.
For example did Vertex's patient selection procedure for Advance result in an easier-to-treat sample than in Merck's equivalent Sprint-2 study? Different SVR rates in the randomly assigned placebo arms would show this effect. For Advance, 361 pts were assigned placebo and 166 reached SVR( 46%). In Sprint-2 363 pts were assigned placebo and only 137 reached SVR (38%). How likely is an 8% difference to arise by chance alone in samples of that size if there were really no difference in patient screening?
Applying the equation from that Yale stat page above gives a 95% confidence interval of (0.01, 0.154) Interestingly the CI does not include zero suggesting that for samples that large an 8% difference is unlikely by chance alone - but the lower bound is close to zero (they cheated, but only a little bit?)
The same approach could be used to sort out whether the difference in SVR rates among naives between tela and boce could easily have arisen by chance or suggests separate underlying distributions (haven't done this).
"Andiamo: though you didn't clear until w20 it looks as if you'd still be classified as a relapser by the Vertex criterion so your odds with them would have been about 80%."
That would have been evident after the Prove 3 trial, not before when they accepted me into the trial with no data at all on prior treatment.
"Agreed that confidence intervals (which incorporate the standard error) are more informative than point estimates. For example, it makes no sense that a lead-in would reduce your SVR odds. The improvement may be small but shouldn't make things worse. "
Publishing the standard deviation would give us a better understanding of how to interpret the numbers. For example: if the Telaprevir trial had results that showed SVR rates of 78% with a lead in and a standard deviation of +-3% then the results would read SVR rates of 75 - 81%. If Telaprevir had results of 75% with a standard deviation of +-3%, then there results would read between 72 - 78%. These numbers are within the standard deviation of the trials and are statistically identical.
That would have been evident after the Prove 3 trial, not before when they accepted me into the trial with no data at all on prior treatment.
"Agreed that confidence intervals (which incorporate the standard error) are more informative than point estimates. For example, it makes no sense that a lead-in would reduce your SVR odds. The improvement may be small but shouldn't make things worse. "
Publishing the standard deviation would give us a better understanding of how to interpret the numbers. For example: if the Telaprevir trial had results that showed SVR rates of 78% with a lead in and a standard deviation of +-3% then the results would read SVR rates of 75 - 81%. If Telaprevir had results of 75% with a standard deviation of +-3%, then there results would read between 72 - 78%. These numbers are within the standard deviation of the trials and are statistically identical.
Wouldn't you need to use multiple trials and calculate the difference between each of them for the same values? Since this is a sample population of a larger group, isn't there a slightly different formula where you need to subtract 1 from the denominator?.
In any case, one standard deviation is likely to make some comparisons irrelevant, don't you think?
In any case, one standard deviation is likely to make some comparisons irrelevant, don't you think?
coeric: anyone doubtful about whether triple tx will work given their past ifn response should look at the data directly - it's well summarized and the difference is stark. The 90-page Merck submission is at
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM252343.pdf
The SPRINT-2 results (naive, 1097 pts) are in Table 8, pg. 42 and the RESPOND-2 results (previous tx failure, 413 pts) are in table 15 pg 53.
Having a 1 log drop by w4 makes approximately a 40% difference in SVR outlook - nothing vague about that.
Any early cutoff decision will exclude some potential SVRs - even continuing with detectable VL at w24 leaves a 2-3% chance of SVR. And for many continuing with a 30% chance will still be the right choice. However it's good to know what you're signing up for.
Testing earlier can give an early peek at how it plays out ( I tested at 24h and 48h post) but there's no equivalent data similar to what's given in those two tables. Hopefully Vertex will at some point let us know their side of the story.
Andiamo: though you didn't clear until w20 it looks as if you'd still be classified as a relapser by the Vertex criterion so your odds with them would have been about 80%.
Re standard deviations, you're right that they don't appear to be explicitly included but since what's being measured is a difference in response rates they are easily calculated from counts. The standard error of the difference of two response rates is
sqrt( (p1*(1-p1)/n1+ p2(1-p2)/n2 )
where p1 = svr1/n1 and p2=svr2/n2 are svr %s in the two groups.
Agreed that confidence intervals (which incorporate the standard error) are more informative than point estimates. For example, it makes no sense that a lead-in would reduce your SVR odds. The improvement may be small but shouldn't make things worse.
In fact looking at the confidence intervals coeric quoted above shows that the CI for the partial responders is much wider (over twice) than the CI for relapsers, making that point estimate more suspect. Of the 662 pts in the REALIZE, 354 were relapsers but only 124 partial responders so you'd expect a noisier estimate in that subgroup.
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM252343.pdf
The SPRINT-2 results (naive, 1097 pts) are in Table 8, pg. 42 and the RESPOND-2 results (previous tx failure, 413 pts) are in table 15 pg 53.
Having a 1 log drop by w4 makes approximately a 40% difference in SVR outlook - nothing vague about that.
Any early cutoff decision will exclude some potential SVRs - even continuing with detectable VL at w24 leaves a 2-3% chance of SVR. And for many continuing with a 30% chance will still be the right choice. However it's good to know what you're signing up for.
Testing earlier can give an early peek at how it plays out ( I tested at 24h and 48h post) but there's no equivalent data similar to what's given in those two tables. Hopefully Vertex will at some point let us know their side of the story.
Andiamo: though you didn't clear until w20 it looks as if you'd still be classified as a relapser by the Vertex criterion so your odds with them would have been about 80%.
Re standard deviations, you're right that they don't appear to be explicitly included but since what's being measured is a difference in response rates they are easily calculated from counts. The standard error of the difference of two response rates is
sqrt( (p1*(1-p1)/n1+ p2(1-p2)/n2 )
where p1 = svr1/n1 and p2=svr2/n2 are svr %s in the two groups.
Agreed that confidence intervals (which incorporate the standard error) are more informative than point estimates. For example, it makes no sense that a lead-in would reduce your SVR odds. The improvement may be small but shouldn't make things worse.
In fact looking at the confidence intervals coeric quoted above shows that the CI for the partial responders is much wider (over twice) than the CI for relapsers, making that point estimate more suspect. Of the 662 pts in the REALIZE, 354 were relapsers but only 124 partial responders so you'd expect a noisier estimate in that subgroup.
I think a lead in is imprecise at best as a screen. I was a slow responder and became undetectable at week 20. I relapsed after EOT. I was a very rapid responder when I treated with triple therapy and am SVR 3 years post treatment.
The data presented is too vague to use as a way of seeing the effectiveness of a lead in as a screen. I have not seen the standard deviations published for any trial, so I assume it's large enough to make the differences between a lead in and no lead in meaningless. I don't have any proof of that, but a trial of a few thousand people used to predict the response of a few million people must have a large standard deviation. If it's +- 5% then a difference of up to 10% between 2 trials is meaningless. I hope it's not that large, but who knows? And that's saying the trial selection is totally unbiased and I don't think many people believe that.
Eric
The data presented is too vague to use as a way of seeing the effectiveness of a lead in as a screen. I have not seen the standard deviations published for any trial, so I assume it's large enough to make the differences between a lead in and no lead in meaningless. I don't have any proof of that, but a trial of a few thousand people used to predict the response of a few million people must have a large standard deviation. If it's +- 5% then a difference of up to 10% between 2 trials is meaningless. I hope it's not that large, but who knows? And that's saying the trial selection is totally unbiased and I don't think many people believe that.
Eric
thank you. you have a great point about screening people out of therapy with a lead-in. Do you suppose there are patients in the boce trials that would have achieved SVR if they had been allowed to continue?
your points are relevant. i am thinking that a shorter than 4 week lead-in might be better. a while back i recall a study that suggested interferon response and SVR could be predicted with-in 24 hours after the first interferon shot.
it might be useful to know my response to interferon/ribivirin to facilitate response-guided therapy. say instance i have a weak interferon response and after 2 weeks of innterferon/ribavirin the viral load is reduced only 75%. and at this point i want to continue on. the way forward might be to try to maintain a significant dose of ribivirin with the aid of epogen when the anemia kicks in. on the other hand suppose by some miracle i am undetected by 2 weeks. i might be more inclined to reduce the ribavirin when the anemia starts.
i am also experiencing loss of attention. don't know whether its due to advancing age or this silly disease. i want to thank all the folks like yourself who have been cured and continue helping us newbies out. thank you one and all.
eric
your points are relevant. i am thinking that a shorter than 4 week lead-in might be better. a while back i recall a study that suggested interferon response and SVR could be predicted with-in 24 hours after the first interferon shot.
it might be useful to know my response to interferon/ribivirin to facilitate response-guided therapy. say instance i have a weak interferon response and after 2 weeks of innterferon/ribavirin the viral load is reduced only 75%. and at this point i want to continue on. the way forward might be to try to maintain a significant dose of ribivirin with the aid of epogen when the anemia kicks in. on the other hand suppose by some miracle i am undetected by 2 weeks. i might be more inclined to reduce the ribavirin when the anemia starts.
i am also experiencing loss of attention. don't know whether its due to advancing age or this silly disease. i want to thank all the folks like yourself who have been cured and continue helping us newbies out. thank you one and all.
eric
I apologize for these scattered posts: I have severe insomnia and ADD that has plagued me since I treated with SOC in 2002.
I think we have to analyze how many people that would SVR were screened out due to the lead in test; in other words what errors took place in the screening process. I think enough data is there to do it, but it's beyond my ability these days. The question is what percentage were screened out in the Boceprevir trial and how does that compare with the failure rate when there is no lead in screen?
Given the standard deviation of these trials, say 5%, which we can only guess at, the results of the two trials are identical.
Lots more analyses here before we conclude that a lead in is beneficial. I wish I could do it :(.
I think we have to analyze how many people that would SVR were screened out due to the lead in test; in other words what errors took place in the screening process. I think enough data is there to do it, but it's beyond my ability these days. The question is what percentage were screened out in the Boceprevir trial and how does that compare with the failure rate when there is no lead in screen?
Given the standard deviation of these trials, say 5%, which we can only guess at, the results of the two trials are identical.
Lots more analyses here before we conclude that a lead in is beneficial. I wish I could do it :(.
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