12 versus 24 weeks For Geno 2's -- The Italian Study What It Actually Says

[jmjm530]

Whether you agree of disagree with the conclusions of the Italian Study, it's important that we at least agree on what the study actually says.

Recently, some here have suggested that the relapse rate is higher in the 12-week (short course) group as opposed to the 24-week group. This statement is misleading.

What the study actually says is "The rate of relapse among patients in the variable-duration group treated for 12 weeks was not different from that among patients in the standard-duration (24-weeks) group with an early response." Therefore, whatever differences that might have occured regarding relapse are not relevant to the two groups we are comparing -- those early responders who treated for either 12 or 24 weeks.

Again, the purpose of this post is not to start another discussion on whether selected geno 2's and 3's should treat for 12 or 24 weeks --  although I'm sure it will. :) The main purpose is to clarify what the study actually says.

Of course, whatever we state here has to be a simplification. I strongly suggest to anyone considering a short-course treatment -- or anyone else interested -- to order the study in its ENTIRETY. It costs ten bucks and can be accessed online here:
http://tinyurl.com/a5ned

The conclusion of the study for those not familiar is that 12 weeks is as effective as 24 weeks for those non-detectible at week 4. This study was done with Peg Intron and I believe a German study concluded the same thing with Pegasys but they treated for 16 weeks instead of 12.

-- Jim

[jmjm530]

Related to the above are statments suggesting that once you re-treat and fail, subsequent treatments will be less likely to succeed because the virus will have "mutated".

I have still not seen any evidence/studies supporting this, and in fact -- with the Italian Study -- 90 per cent of those who failed treatment, and were then re-treated, achieved SVR. This rate is consistent (actually a little better) than with the naive tx population. A small sampling of geno 2's and 3's but interesting none the less.

-- Jim

[v eggie dip]

hehehe  Jim you're a gluton for punishment buddy!  posting that will most definately "ruffle feathers" and you know YOU will be under attack!  But, that's the burdon a man's man has to hold I guess *wink*

Has the B-12 helped yet?

*dipper*

[GoofyDad]

You knew you'd be hearing from me :) BTW, what's the title of the German study (or author would help).

This thing reads like a study in contradictions. Take the following 3 statements for example:

"The rate of relapse among patients in the variable-duration group treated for 12 weeks was not different from that among patients in the standard-duration (24-weeks) group with an early response."

"The rate of relapse (defined as HCV not detectable at the end of treatment but detectable at the end of follow-up) was 3.6 percent in the standard-duration group and 8.9 percent in the variable-duration group (P=0.16)"

"The proportion of patients with relapse was higher among those treated for 12 weeks than those treated for the standard 24 weeks"

I think we sometimes forget the random nature of this treatment. Take the following. One would certainly expect near identical responses for the non-4-week-responders in both groups, but this is maybe the largest differential in the whole study:
  
"...continued treatment in patients with viremia at week 4 resulted in response rates of 50 percent among those
in the standard-duration group without an early
response and 72 percent in the variable-duration
group treated for 24 weeks (P=0.13)"

As I mentioned before, I believe (either for genos 2 & 3, or just geno 3) 4-week-responders faired worse overall, even those treated for 24 weeks, than did non-4-week-responders treated for 24 weeks. I'll have to dig that out later though.

Let the feathers fly!

[GoofyDad]

Yeah - Couldn't agree more. I noted that same observation in the prior thread by  healed24. Also posted a link to an article that said in part that viral loads spiked after relapse, then returned to pre tx levels in a matter of a few weeks.

[cuteus]

and there were some differences that get overlooked, of course if you are one of the unlucky ones to relapse, you have to re treat and go the longer route for a total of 36, why not do the 24 if your life is not in danger?

At first, early responders -- those who had undetectable levels of hepatitis C virus after four weeks of treatment -- looked the same in both the standard and variable treatment groups. Ninety-three percent of early responders treated for six months and 95% of those treated for three months still had no detectable virus at the end of treatment. Six months later, that percentage dropped from 93% to 91% in those treated for six months.

But it dropped from 95% to 85% in those treated for three months.

the poor horse has been beaten over and over...

[jmjm530]

It's interesting how different people can look at the same study and come up with a different reading. I'm assuming you read the study in its entirety?

Anyway, this is exactly why I posted the link to the full-text report. Hopefully, people vested and/or interested enough will take the time to go over the report and draw their own conclusions, or at least share it with their doctors.

To me, the report was clear that the relapse rate in the two relevant groups was identical as was the rate of SVR.

Not trying to beat this poor horse to death, not am I endorsing the report, but rather trying to clear up what seemed to me some misconceptions.

This study, like many others, is not the end all, but certainly something to be seriously considered in the mix of things. The more we understand, the better we can fight this thing.

-- Jim

[jmjm530]

You bring up some interesting points that could be debated on and on. That's exactly why I posted the link to the full-text study so people can go to the source and make up their own minds. But the way I read it -- if you put all the this-and-that's aside -- the conclusion is very simple: 12 weeks is as effective as 24 weeks in geno 2's and 3's who clear at week 4. As far as ripping the study apart, not sure too many of us here have the credentials for that. Again, I'm not endorsing the study, just trying to clear up some misconceptions about what it actually says. Obviously, I'm not doing such a great job. LOL.

-- Jim

[jmjm530]

As Freud was fond of saying, sometimes things are exactly as they appear. Other than your friend, how many women do you know that sign their name "Jim". LOL. Certainly I'm not one of them.

-- Mr. Jim

[GoofyDad]

"the poor horse has been beaten over and over..." well, at least he's used to it by now, so let me get my stick out! :)

"Six months later, that percentage dropped from 93% to 91% in those treated for six months"
OK - So being in the variable group and treating for 12 weeks seemingly adds to your chance of relapse.

"response rates of 50 percent among those
in the standard-duration group without an early
response and 72 percent in the variable-duration
group treated for 24 weeks"
OK - But being in the same variable group, in and of its self, seemingly gives you an even more significant edge should you not meet the 4-week test. Sign me up for the variable treatment - just commiting to it seems to help alot when you don't have an early response and end up treating for the full 24 weeks!

Obviously, random chance gave the 12 weekers in the variable group some disadvantage compared to the fixed length group, and the 24-weekers in the variable group some advantage over their couterparts in the other group.

Flip a coin 200 times. If you don't get 100 heads and 100 tails, what conclusion should you draw? I'm not a math-head but I'd guess a 115(H)-85(T) distribution on 200 flips would be perfectly within expected range. Then would we all start quacking? Go with heads, its proven to be 30% more effective. Go with tails, heads is worn out, the time for tails is NOW!    

[jmjm530]

Your post reminded me of a great Jack Nicholson quote in the movie "As Good As It Gets". If you remember, he plays a writer who writes about women.

Anyway, the question is posed to his character in the film:
"How do you write women so well" ?

Nicholson's character responds: "I just write a man, then take away all accountability and responsiblity."

-------------------



-- Mr. Jim

[GoofyDad]

For the record. I agree. The study serves to show there is no statistical DISADVANTAGE to a variable treatment approach. The rest of it is noise.

[rifleman]

Of course, the 12 week course is an OPTION for those 2's & 3's who clear at 4 weeks.  Everyone getting tx for hep C has a doctor, so run it by them and make your own decision.
DJL

[v eggie dip]

ohhhhhhhhh not nice Mr. Jim, you just lost some dipper points by quoting Nicholson tsk tsk.....

Now you have to say 4 times "women are nice" and then maybe you will be redeemed  lol

*the scorned dip*

[GoofyDad]

Sure my doctor will be a key player in any treatment decisions. But that doesn't mean I'm precluded from researching, discussing, and analyzing my options outside of his presence, does it? I mean, I'll get maybe 20 minutes with him on the subject. I'd like to understand it as best I can first. Unreasonable on my part?

[mistybean]

I am glad this is being posted and discussed.  My doc has been talking to me about this study since I started.  I was non-detect at week 5.  We are now waiting on my week 14 results.  If this comes back non-dect he is going to sugest that we stop treatment early.  He feels that most of the 2 genotypes did fine with 12 weeks.  Just a while back we were treating 2's for 48 weeks.  Now we know that is not needed.  I have no opion on this as I do believe the population is not that large.  I would like to see a large scale population study done.  I do have a few friends who were genotype 2 who quit treatment 2 months early because they could not stand the treatment and are SR today.  Being an early responder at 5 weeks and a genotype 2.. it would make my day if I could get off early.  But again.. I really don't see enough studies that makes me think I should go off early.  My heart and part of my head seems to think I will be ok if I retire treatment at 20 weeks.  This is not a study just a gut.  In the meantime, I am on week 15 and waiting on new PCR results. ed

[jmjm530]

Chev,

No one really does a great job in changing opinions that are already made up. And this works both ways. My intent was not to change anyone's mind but to provide info for those who either hadn't heard of the study or are still on the fence. Like Rifleman, so succinctly said, it's an OPTION.

BTW back to the gender confusion  thing... I guess you missed this thread...
http://www.medhelp.org/perl6/hepatitis/messages/39577.html




-- Jim

[jmjm530]

No, that quote was not directed to you at all. It just popped into my mind about when you brought up gender transperency (or lack thereof) in the written word. I do write for a living (at least when I had a life) so possibly I've "neutered" my writing over the years to make it more professional. Or perhaps, my inner woman is just yanking to get out. Something to discuss with my shrink next time. LOL.

-- Jim

[cuteus]

misty, that is my opinion also, there are not enough studies that suggest this course of tx, and NONE with the american population which seems to have their own specialty hcv plus their own set of lifestyles that might give an entirely different result.
The comment I posted was made by a published physician, who I am sure studied the article in its entirety before publlishing yet another medical article.  He did not concur with jm's reading of the study, so, yes, read, run thoughts by your GI and in the end, follow your gut feeling.
You will do just fine.

[rifleman]

I guess I forgot about the side effects of ribavarin.  Self-determination?  Oh the horrors!  Lenin must be rolling in his grave.
DJL

[cuteus]

and for those geno 3, the study also concluded:
The researchers also examined possible differences among patients based on genotype. In those with HCV genotype 2, the overall success rate was 80%, compared to 66% among those with genotype 3.

that was the overall rate, what was it for the short duration group, I wonder.

[jmjm530]

Cuteus said prev: "The researchers also examined possible differences among patients based on genotype. In those with HCV genotype 2, the overall success rate was 80%, compared to 66% among those with genotype 3.

that was the overall rate, what was it for the short duration group, I wonder."

---------------------------

Identical success rate for geno 3's in short-duration versus long-duration group, as identical success rate in geno 2's. It's all in the *full-text* study should you want to view the source. BTW it's really more complex than geno 2's and geno 3's having different SVR rates. It has to do with geno 3's SVR's being more sensitive to pre-tx ALT levels, at least according to this study.
BTW most doctors are too busy to read the complete text articles and simply rely on abstracts -- even those that review things. Whenever I bring the full-text to my doctor, they always ask for a copy. LOL.

-- Jim

[jmjm530]

OK. That last one was for free. Any more questions and you have to fork out $10 for the full-text report like I did.:)

The purpose of my original post was not to debate this topic but to clarify what the study actually said. Based on discussions like this, I came to the conclusion that the only way to accurately reflect the studies content was for people to read the original full-text themselves --  not rely on abstracts or third party opinions.

-- Jim

[cuteus]

maybe you can sell us a discounted version?

I can't see a physician that is going to publish an article in a reputable medical site, relying on only opinions, It would discredit him as an "expert", don't you think, open him up to ridicule. I was not speaking of a dr in practice which is hands on with patients and with no time to read everything available.
Abstracts will present a condense view of the most important findings in a study, so they are not to be discounted entirely.
I would like to see the american's experts opinion on this study and so far have only found the study parroted in site after site, except for the one where this physician published his view. I also want to see the study replicated with americans, before promoting it as a comparable choice to achieve SVR.
If you can come up with favorable reviews on the application of this study to the American version of the virus. let us know.

[jmjm530]

The study was published by a very reputable AMERICAN :) Journal -- actually *extremely* reputable -- New England Journal of Medicine and not "parroted" but re-printed in part on all the important Dr. run hepatitis sites.

Sometimes these sites do what I consider superficial "reviews" and sometimes they don't, but I don't share with you the thoroughness of many of their comments. Often, an editor takes a quick take on the study and concludes with something like "we will be following this very carefully." Hah !

Well..I emailed one of these folks once about a study done three years ago where the big shot medical editor wrote "we will follow this very carefully" and guess what -- there was no follow-up articles in three years,  and his email indicated that he gave it no follow-up thought.  LOL.

Not sure where I'm going on this except to say that a single short peer review article doesn't say all that much. The study is the study. But more important, as has been discussed in the other threads, these studies present OPTIONS they are not mandates.

I'm not saying that everyone should run out and follow the Italian study. But I also don't think the study should be dismissed outright just because you can't find a recent review or because it was done with Europeans and not Americans. Yes, that should be factored into the decision making process, but much of our data initially came from European studies, and in fact many of you who are on peg right now are probably doing it because of data collected in Europe.

And frankly, the study is so recent that what can a review really say EXCEPT parrot the study. For any new information, the study would have to be repeated. And that will be great if and when it happens in this oh so fast changing field, but in the real world, most top researchers are busy now with the sexy protease inhibitors so we may have to wait, just like some of are waiting for the Swedish high dose riba studies to be duplicated here. My guess is by the time that happens, riba won't even be used in tx anymore. :) Point being that sometimes in this rapid-moving field we have to make judgement calls on yes, information/studies less complete than we'd like. Otherwise, we'd all probably still be on monothreapy. :)
_________________________________________________

Regarding the full-text article -- possibly we can work something out. I take cash, MasterCard, Visa. No AMEX, Discover Card or personal checks. Actually, I'd email it to you for free but I'm afraid you'd pull all the negative quotes out of context and post them and then I'd be obliged to write some more on a topic I've about run out of steam on. :)


-- Jim

[GoofyDad]

"most top researchers are busy now with the sexy protease inhibitors"

Guess the word's not out yet, the PIs only work on
Europeans :):)

Parlez vous a Lu-Lu Bleu?

[Forseegood]

Just wanted to say my person I spoke with here in the US is on the vertex PI study and he's just on the interferon w/the drug alone (no riba.)

[GoofyDad]

Interesting. I wonder why vertex is including INF? I guess combo has a higher probability than mono therapy. Maybe CTOANN will drop by and offer his thoughts.

[Forseegood]

at least you called me forsee instead of the word alluding to the prepuse. he he he.  Talk about the all the gender confusion around here lately....we need pics!

[jmjm530]

It has to do with some legal/ethical but probably mostly FDA approval issues. In other words, it's very helpful for new drug trials to get green-lighted when they initially combine with a proven therapy, i.e. Inteferon. Later trials will try Vertex as monothreapy.

[GoofyDad]

Would that be prepuse, the <a href="http://www.bandliste.de/modules.php?name=Bandliste&bandsop=info_bands&band_id=4467">glam rock band</a>;

or prepuce, the <a href="http://www.cirp.org/library/anatomy/cold-taylor/">wienie band</a>?

Goofy - just havin' some fun - as long as you forced me to look it up....

[rifleman]

I think that the reason for the interferon is that it is the muscle drug that kills the virus, and the Riba (or in this case the new drug) prevents the virus from coming back.  I found interferon pretty easy to get used to, but that riba was some nasty stuff.  If the new drugs are better than riba and are well-tolerated, that's just great.
Got my 6 week post tx bloodwork results back today.  ALT is perfectly normal and the rbc's etc have all gone back up where they belong.  
DJL

[GoofyDad]

Congrats on the bloodwork. I know we're all pulling for your SVR.

I understand the Peg/Riba mix, but in the case of vx-950, it seems to slaughter the buggers all by itself - like INF, but maybe better. It would seem more logical (to me who ain't so logical) to mix vx-950 for the same stick and move punch as we have with the current combo therapy.

Of course, if you're marketing a new conbo, I could see why you'd avoid bringing riba into the mix unnecesariliy. I could also see why you'd rather not stick vx-950 out there 'naked', till you really-really had a sense it could complete the SVR on it's own.

Of course, if you have engineered a drug from the ground up, you probably have a better idea for how it should be deployed than does this meat-head.

Mindless musings that make no difference at all.......

[Forseegood]

I thought that the interferon sets up the immune response for the viral drug (in this case the vertex drug) to go in for the sustained kill; but then I barely made it through biology. In having talked to one of the biologists who invented it, he said that yeah, in all the inside trials that they have tested, the vertex does kill the critters really, really fast, I mean, people go svr within a week in some cases, I guess now they are just focusing on the sustained kill?, so that's where the interferon comes in? dunno for sure, you might be the right one Jim. The guy who can't think of a nickname is following it more closely then I am.

Hey goof, you don't even ever have to say your kiddin! Hopefully, I got what's popularly known as a sense-of-humor. You better have with these cooties we're all dealing with. As P. Benatar has inimitably said.."hit me with your best shot."

Rifleman: great news! ouuu haaa!

[jmjm530]

Think you got it man! Six weeks is almost as good as six months -- like better than 90 per cent of SVR if your PCR follows ALT which it tends to. You the man. The RIFLEMAN :)


-- Jim

[jmjm530]

That's plan "A" -- knock the virus down fast with Vertex and then finish the job with Peg and maybe riba. Follows very much the idea that RVR (rapid viral response) results in higher SVR rates even with shorter treatment. As I mentioned earlier, this approach was almost required for the FDA to approve trials in this country.

Plan "B" -- and we don't have too much info here yet, at least not public -- will be to go mono with the Protease Inhibitors. Mono in the sense of no peg and no riba, but possibly as part of a anti-viral "cocktail" of other drugs, like they do with AIDS. Plan "B" should be in trial pretty soon if not already.

-- Jim

[Forseegood]

instead of me just speculatin, I should just go check - too lazy. I thought there are 2 or 3 legs of the study, with different figurations, but I know that one is with no riba, according to person I spoke to on the study now. Hey Couldn't Think of a Nickname, where are you???? We need your two cents. I hope youre feeling better Jim, you sound perky to me!

[cougareyes]

That's why the contraversy about the time frame of the new drugs. Yes, vx-950 knocks down the vl fast; but can it maintain svr. That was the same thing with interferon in the beginning. Then they added the riba to maintain the svr, interferon is now doing the job that vx-950 is now doing in trials.
No reports of svr yet, as far as I know; and if they are going to use riba to supercharge svr after vx-950 knocks down the vl; screw that. Riba is one evil drug, that is the drug they need to replace.   Peace

[GoofyDad]

"...the idea that RVR (rapid viral response) results in higher SVR rates"

Except for Italians, apparently.  :(

Oh wait. But I'm not Italian :)  (sorry ladies!)

Non Gooffeppi

[GoofyDad]

We see this through the same colored glasses, Cougareyes. You said more clearly what I tried to say in up in c38. Tripped over my tongue, I guess.

On one hand, if they combo it with riba, they could do well in the US market with all the 1a's - assuming a better SVR rate than today's therapy. But if they can eliminate the riba, the world is their oyster. And why not couple it with peg, what's the harm from a marketing and ROI perspective?  Not to say Jim's FDA theory isn't the guiding force.

[cougareyes]

I'm 1/2 Italian so do you think I could do a 3/4 tx course. Peace

[GoofyDad]

I got what's popularly known as a sense-of-humor

Gee, guess I hadn't noticed. My fault ;-)

"..fire awaaay....."

[GoofyDad]

... I was well on my way to a nonsense free day when you tossed up the pupuse softball. What's a Goof to do?

Deliver me from the jaws of the beast. I try and then I try some more....but is it ever enough? Oh no. They just keep on making me do it!

[rifleman]

Yeah, my ALT was 39.  Before tx it was 54 and during tx it actually went up to 42.  I have read old threads where the relapsers had their ALT up over 100 post-tx.  Didn;t have a PCR b/c the doc said that, even if I had relapsed the virus would take awhile to show up in the blood.  He said don't worry about it and come back in March for a PCR.  If my ALT had been above the normal range, I would be worried.  I understand that it takes several weeks for the ALT to stabilize at a general level.  This is probably because of the havoc the tx drugs themselves wreak.
As for the 950 stuff, maybe you can take a reduced dose of peg.  As far as how they work, my nurse told me that the drugs work in conjunction with each other, that is why you have to ytake your riba for a week after the last shot.  You might not have to do this if you did 38 weeks of tx, but it is a good idea if you do 12.  
Also, I think I heard that 950 specifically targeted geno 1 HCV.  They will have to tweak it for the other geno's, I guess.
DJL

[jmjm530]

I'm half German and half Russian so if history is any guide, half my virus could invade the other half without warning.

-- Jim