SVR rates confusion

[wyntre9]

Let me say up front I'm confused!

I thought I understood about SVR rates but after reading forum the past few days it occurs to me that I may be interpreting everything a** backwards.

Clarification, PLEEZE!

I'm 1A, not UND by week 12, Und around week 16, currently on 72 week TX.

I thought that 1A's who reached UND by week 12 had at least a 50% chance of SVR by doing 48 week SOC.

I also thought that slow responders (ie; those who reach UND between weeks 12 and 24) had an SVR rate of only 29%.

Therefore, my understanding was that slow responders who extend to 72 weeks TX increase their chances of SVR .....  but to WHAT?

I mean, do the studies say 1A's who extend to 72 weeks have a 50% SVR rate?  Is it 70%?  29%?

Does anyone know?

Wyntre

[orphanedhawk]

Confunsion, another word for tx??

I hope this link helps.   Take care.        OH

http://www.hivandhepatitis.com/2007icr/easl/docs/042407_a.html

Selected Patients with Genotype 1 HCV May Attain SVR by Extending Treatment Duration to 72 Weeks

[Bill1954]

Hi Wyntre;

Here is an overview by Liz Highleyman from the J M Sanchez-Tapias data (I believe it’s from the Teravic 4 study, actually).

http://www.hivandhepatitis.com/hep_c/news/2006/082906_a.html

An excerpt from the study: …”Looking only at the genotype 1 patients with detectable HCV RNA at Week 4, 44% of those treated for 72 weeks achieved SVR, compared with 28% of those treated for 48 weeks (P = 0.003)…”

You’ll need to browse through the article, but I think this is the pertinent data you’re looking for (one source at least).

For reference, here is the Sanchez study itself:

http://www.natap.org/2004/EASL/easl_06.htm

And more info from Berg:  

http://tinyurl.com/2bjymn

I hope you’re feeling a little better; I had some treatment issues in weeks 35 to 40 that seriously taxed my sense of humor, but now at week 51, life’s pleasant again. Hopefully you were just going through a phase.

Take care,

Bill

[wyntre9]

Yeah, I've seen this but it doesn't say anything about percentages.

Thanks anyway.

wyn

[wyntre9]

Thanks, Bill.

What's a sense of humour?  *LOL*

These are exactly the stats I was looking for although they're NOT nearly as encouraging as I'd deluded myself into thinking.

Only 44% get SVR after 72 weeks?

Jeeezzzz . . . And I thought it was 72% after 44 weeks.  (just kidding. I'm mathematically dyslexic)

No, seriously, I did think the SVR rates WERE closer to 70% with extended TX.

I was right.

I was wrong again.  :(

How are you holding up now?  I seem to be going through the 35-40 week TX Blues.

wyn

[Bill1954]

You posted above:

…” Therefore, my understanding was that slow responders who extend to 72 weeks TX increase their chances of SVR .....  but to WHAT?..”

“WHAT” = 44%, according to the interpretation by Liz Highleyman of Sanchez-Tapias.

(At least that’s my interpretation of L. Highleyman’s interpretation of Sanchez-Tapias’s interpretation, Lol!)

[FlGuy]

...and translated from the original Spanish, I guess.

[wyntre9]

I just read through both links (thank you very much) and realized my mathematical dyslexia combined with regular dyslexia must have somehow translated THIS:

"18 Months Therapy (Pegasys+Ribavirin): study found relapse rate reduced by 70%; viral response rate in genotype 1 increased by 50%"

into MY fantasy cruising on De Nile wish that 72 weeks = 70% SVR whereas 48 weeks = 50% SVR.

Doya think I might have a future in advertising?

wyn

[Bill1954]

Wyntre;

Our posts are crossing; you might have misinterpreted this data that suggests:
~~~~~~~~~~~
“…Among the Week 4 HCV RNA undetectable patients, SVR rates were 79% in the arm treated for 24 weeks (i.e., genotype 2 or 3) and 64% in the arm treated for 48 weeks (i.e., genotype 1)…”
~~~~~~~~~~
Unfortunately, (according to this study, anyway) once a GT-1 patient does *not* achieve UND status by week 4, they start to breath different air. Increasing ones statistical odds from 28% to 44% is enough motivation for me. By the way, I was undetectable to <5 IU/mL by week 8 this treatment… I’m currently extending based on a Hx of prior relapse, as well as my ability to tolerate meds.

I’m doing well, thanks for asking. I’ve got classes 4 days a week right now at the local community college, so I’m staying busy in that department. I do seem to feel apathetic in terms of physical exertion; no running or even walking lately. I mentioned above that I kind of fell in a little hole during the mid-thirties- back on track since week 40, though. I wish you the same, gal.

Take care,

Bill

[jmjm530]

Part of the confusion is that some of the studies listed above used fixed-dose ribavirin (800 mg/day) instead of the weight-based dose many of us use. I haven't reviewed all of the studies lately but I haven't been aware that EVRs (detect at week 4, UND by week 12) who use weight-based ribavrin whould across-the-board extend to 72 weeks. Hey, I was detect at week 4 but UND at week 6 and two prominent liver specialists strongly recommended only 48 weeks. Plus there are other factors that should enter into the equation such as amount of liver damage and how well you're tolerating treatment. On the other side of the coin, if you really feel that the odds drop significantly if your're not UND by week 4, then I think it's just as reasonable to stop treating after 4 weeks as opposed to extrending to 72 weeks in the subset of folks with little or no liver damage. Treating 72 weeks is a long haul with interferon and you just don't know what kind of shape you're going to be left in.

-- Jim

[Bill1954]

Wyntre: too funy!

FL: I'm actually taking second semester Spanish in school; if I had to translate this directly from Madrid, though, I might be arriving with the same stats Wyntre is :-).

[Bill1954]

Thanks for clarifying, Jim;

I was aware of some discrepancies, and was trying to be careful (CMA) by allowing Liz Highleyman to provide the interpretation :o). Yeah, it’s difficult to get apples-to-apples with a lot of this data… it’s almost like ‘pick a position and then find a study to support that position’, huh?

Bill

[wyntre9]

Jm,

I have always looooved, no, treasured your posts but could you Pleeeze make a minor concession to the dyslexic, ADD-afflicted on board and put some friggin PARAGRAPH BREAKS in there!!!!!

i mean, i KNOW it won't technically BE a P. break but it would make it soooo much easier for dolts like me to try and comprehend.

On the other hand, in my case that's obviously futile so why should you bother making that effort?

you're right . . .  

but if i understood your point, it's a good one...  i think. . .

Bill,

You taking classes or giving classes?

Glad you're feeling better, again.  Hope I can say the same sometime soon.

wyn

[jmjm530]

The only thing you can do is print out every study -- full text, not Liz's commentaries -- that is pertinent to your genotype and situation, or as close as possible, and then really study them in detail. I did that with what was available at the time I had to make my decisions, and even then the match-ups were very difficult. I caution people to make these types of decisions by reading snippets here from studies that may or may not match up to their situation. What we learn is is an exellent *starting* point, but certainly not an end point. All these studies (full text) can be ordered online with a credit card or fetched from a medical library. Next step after digesting is to test them against a good liver specialist to get the on-the-street take, so to speak. I know, for example, when I presented data to my doc why I should stop at 48 weeks (based on my RVR) he told me had been seeing lots of relapses lately in the older (that is me) population of those with more significant liver damage. Based on that I extended another six weeks although I must say two other liver specialists told me 48 weeks was enough. So in a sense you're correct -- study up all you can, and then come up with a position and then read backwards to support it because you won't get 100% coherency. The important thing though is to study up, or in lieu of that get in touch with some of the best clinicians out there  which generally means seeing someone at a major teaching center.

-- Jim

[wyntre9]

hope you know i was kidding

wyn

[jmjm530]

LOL. Actually I missed your post but just went back and re-read it. You're right! I usually do use lots of breaks but for some reason haven't lately. Personally, I often don't read posts that go on and on without breaks so thanks for putting up with mine. I'll go back to my older style, def more readable.

Be well,

-- Jim

[Bill1954]

Jim--

Very well thought though comment, Jim; as always. After noodling that for a few minutes, I realized that if a person were really motivated, they could set up a spread sheet/data base for comparative study. It would require source footnotes in each cell to back reference, but a person could build an apples-to-apples comparison fairly easily using their own design criteria. This would be especially useful for formal presentation to a clinician as well. I’ve always relied on memory for this, and failed miserably :o).

I hope life is treating you well, my friend—

Bill

Wyntre;

*Taking* classes, silly girl!! I’m also a self-described ADD/Dyslexic dolt… Lord help any class I tried to teach! I never finished high school, Wyntre. I got sidetracked from school at about 13; right about the same time girls started growing (0)(0)’s, and uh, the rest is history. I did carpentry for almost 30 years, so maybe I could teach a little bit of that. This is just bonehead Spanish 402, and simply for the joy of learning. Thanks for the compliment though; intended or not.

My side effects seemed to run in cycles during my last treatment period also. I had chronic, persistant diarrhea through Tx weeks 32-40 last time; thought it was going to be the end of me. Then I came out of my hole, and felt pretty good for the remaining 16 weeks. This stuff is weird, as you’re discovering first hand :o). I’d guess you have plenty of time left for your side effects to morph into something new and exciting!!

Seriously, I hope you get a break for a while; it makes all the difference in the world. Remember that this is finite; it too shall pass.

Take good care of yourself, and say high to all the feathers for me—

Bill

[cruelworld]

wyn,
it seems to me that if you make 72 with weight based dosing you should have
at least 50% chance of SVR. i think this is a safe conservative number that you can really count on. if you want to predict optomistically then 55%. when my doc originally told me 40% my heart sank and i figured if i could get to 50% i would be happy.
at least its even money. the 70% figure you cite might be a number quoted in
in another post  based on a high riba study. i personally think that number is over optomistic but i believe that my extra riba intake pushes me up to 55% to 65% chance. i had a little better performance than you at 12 weeks but over all we are very
similar. i know you have been having a rough time of it but you ought to try one extra riba a day. i bet you wont even really feel it. if it doesnt agree with you just back off, at least you will know you tried. the shiffman study suggests overwhelmingly that this small riba increase makes a big difference in SVR rates. supporting evidence to this issue is limited so dont bet the farm on it. on the other hand, most of my tx experience  has been positive by using any shred of evidence i can find to be more hopeful about success. its not too late, the increased riba should help even this late in the game, we still have a long way to go. my attitude has been much improved since  reaching the halfway point. i hope this has helped you too. as far as tx being worse or better as i go, i cant really tell the difference, as it all seems overly horrible and my ability to compare horrible to horrible is impaired anyway!

bill,
72 thousand million years of all out double dosing! they dont make em like you any more! at least you got cleared by week 8 and thats got to help mentally. i cant imagine that you are tolerating as well as you appear. your death march has got to be brutal and beyond. you make us invincible warriors seem like trainees!
this too shall pass eh? i wish that was true for me, as my whole life seems to be one giant rolling disaster. im sure just as soon as i beat this demon a ten times more gruesome one awaits me! oh well at this stage im so good at surviving disaster this doesnt seem too bad. i guess i probably deserve it so i really dont mind paying the
price. OUCH!

good cheers to all as we continue our medical pilgrimage to salvation.

hey your hairdo is messed up  HA HA HA HA HA HA HA HA

[Valtod]

Wyntre wrote: "I mean, do the studies say 1A's who extend to 72 weeks have a 50% SVR rate?  Is it 70%?  29%?"

I think your confusion is caused by mixing up the SVR chances of the WHOLE group and a 'difficult-to-cure' SUBGROUP of it - the delayed responders. Also, you're probably mixing up SVR rate and RELAPSE rate.

First of all, as Jim suggested above, you should do some 'matchmaking' between your particular case and studies (with groups and segments of groups) that most closely resemble your baseline and treatment situation. I only know that you're genotype 1a, high viral load, delayed responder on Pegasys and weight-based RBV. So, all the studies about other genotypes, studies not differentiating delayed responders, PegIntron studies or Pegasys and fixed dose RBV (800 mg) studies are NOT good match for you. (The influential Berg study is among them because it's fixed dose RBV.)

Ferenci study is a good candidate - it uses weight-based RBV and specifically deals with delayed responders and extenders. (It also achieves better SVR rates than the studies in the USA, probably because the European patients have generally better predictive factors for SVR - younger age, less fibrosis, lower BMI.)

Please look at this diagram from the Ferenci study:
http://www.natap.org/2006/images/110606/Figure3-4.gif

The first red column is ALL the 48-weekers - 94 people G1. 54 of them achieve SVR.
So 54/94 = 57% SVR rate.

Before Tx, each one of these 94 people has the expectation for 50-60% SVR. But at the end of Tx, the group is split in 3 distinctive subgroups (94 = 16+59+19):  
16 non-responders drop-outs: 0/16 = 0% SVR rate (not on the chart)
59 early responders (by week 12):  47/59 = 80% SVR rate (second column)
19 delayed responders: 7/19 = 37% SVR rate (third column)

I hope now you easily see how 3 groups with SVR rates 0%, 80% and 37% respectively, when taken together, give us a cumulative SVR rate of 57%.

Fortunately, you're not in the first group of non-responders. Unfortunately, you're not in the majority either - the second group of early responders.  You're in the third group of delayed responders with RELAPSE rate 100% - 37% = 63%.

Now if you look at the pink columns of the 72-weekers, you see a cumulative SVR rate of 59% which, when broken down, gives 82% for early responders (by week 12) and 77% for delayed responders.

I hope you can see why for the WHOLE undifferentiated group of G1 patients, extending treatment is not really beneficial (57% is comparable to 59% SVR).

The same argument holds for the early responders (80% is comparable to 82%).

However, for the small fraction of 13 delayed responders, the extend treatment regime brings a SIGNIFICANT benefit - a two-fold increase in SVR rate from 37% to 77%. The RELAPSE rate falls to 100%-77% = 23%.

Again, this is a European study with very optimistic SVR rates for both early responders and delayed responders. Using an American study with 'difficult-to-cure' patients, I corrected the SVR rate of delayed responders on SOC (48 weeks) from 37% to 31%.
(The correction is calculated here http://www.medhelp.org/forums/hepatitis/messages/44014.html )

In your case though - being a woman, relatively young, with minimal fibrosis - if you have a normal BMI and no other negative predictive factors, your profile may match nicely Ferenci's group of delayed responders, so his optimistic SVR rates may apply for you.

On the other hand, if you have a higher BMI or another negative predictive factor, you should lower your SVR expectations, as most of the American delayed responders (like me) should do.

I hope this helps :-)

[jmjm530]

Valtod makes some good points -- again on trying ones best to match up your stats to study stats. Not only does this exercise give  you more accurate/relevant data to analyze, but it makes your job a lot easier -- i.e. not having to wade through tons of studies. On a personal note, I became very knowledgeable in geno 1 RVRs and their options, for the simple reason I was a geno 1 RVR. I notice Valtod is a slower responder on his second treatment, and no doubt accounts for his knowledge and interest in extended regimens.

In doing this type of research, getting the full-text articles is very important, as is crticial analysis of what is being said. For example, in doing some quick lookups for this thread I came across another study which was much more pessimistic than the Ferenci study Valtod posted. http://www.natap.org/2006/AASLD/AASLD_32.htm

After scratching my head because the results didn't match up, I decided to re-read the entire study (actually a summary in this case) and found that the authors used a very difficult to treat group, not at all representative of the Hep C population as a whole. They stated in part:

"Overall, 48% of patients were African-Americans; 79% had high viral load; 24% had F3/4 fibrosis, and 31% had a body mass index of 30 or above. "

Fortunately, this info was included in the summary, but sometimes it's not and that's where full-text comes in.

Another thing to look at in studies are intent-to-treat stats versus per protocol stats. If you're following the protocol (full compliance, full distance) then per protocol would match up better. However, if you're just starting out -- or don't know how you will fare -- you should look at both. (For example, per protocol figures can be deceiving in a trial with significant drop out rates). Yet, often its hard to figure out which population is being talked about unless you take the time to find out.

Lastly, often you simply won't get an exact match up. I know I didn't. I was an older (only 58 but my doc called me 'older' per tx population :) ) male, geno 1, with significant fibrosis, yet an RVR.

Impossible to find any exact matchups reconcilling what some considered some negative pre-tx predictors versus RVR (or almost RVR as I didn't UND until week 6). And then I double-dosed and did high dose ribavirin, so how exactly did that fit in?  

That's where formulas like Drusano, modifications thereof, and other formulas like Valtod are working on comes in. All attempts at individualizing treatment length working between the various studies. Or to paraphrase one doctor, treating outside the standard cookbook.

Also that's where consulting with one or more top docs come in. Taking advantage of their clinical experience and real-world comparisons of study data versus on-the-ground data. Assuming of course, that the doctors are as well versed in these studies and hopefully you will be. Surprisingly (and quite disturbingly)  this is not often the case.

Put it all together and hopefully you'll come up with a number that's just right for you. Sort of like that "Sleep Number" bed they advertise on TV.

Part science, part art and no doubt part luck. But so far it's the best we can do until more critical tests are developed to determine if the virus is truly gone or permanently suppressed (take your pick) before we stop taking the the treatment drugs. If/when those tests are developed, then we no longer would have to cross our fingers after our last shot of Peg.

-- Jim

[beamishboy]

art ,science,statistics......i wish y'all SVR!!...GOODLUCK

[Valtod]

I see we already went through all this just 3 months ago:
http://www.medhelp.org/posts/show/98287
Please see my post in the thread where I list links to studies.

There's no new and groundbreaking data about slow responders and extended Tx in the last 3 months, so everything said then still holds true.

If you check out Sanchez-Tapias presentation (especially page 18), you'll see they use fixed dose RBV (only 800 mg):
http://www.vhpb.org/files/html/Meetings_and_publications/Presentations/MADS62SanchezTapias.pdf

No one of us here is on fixed dose RBV and some are pushing even higher than weight-based doses. So the 44% rate of SVR - in Bill's interpretation of L Highleyman’s interpretation of Sanchez-Tapias’s interpretation - has nothing to do with Wyntre, Bill himself, me, or anyone else here doing 72 weeks.

On the other hand, here are some studies of 72 weeks Tx WITH weight-based RBV:

http://www.natap.org/2007/EASL/EASL_32.htm
Mangia - only 13% relapse ratio (33 SVR and 5 relapse)

http://www.natap.org/2006/AASLD/AASLD_34.htm
Ferenci - 23% relapse ratio (10 SVR and 3 relapse)

http://www.hivandhepatitis.com/2007icr/ddw/docs/061507_a.html
McMahon - 0% relapse ration (ALL 4 prior relapsers are SVR now!)

http://www.medhelp.org/posts/show/298214
This Forum  - all 8 known 72+ weekers between 10/03 and 2/07 are SVR now:
DoubleDose, layla, mikesimon, Cuteus, Eisbein, Lonestar823, Jaroman, NYgirl
This is 0% relapse ratio!

I know the last one may look not very reliable, but someone has to find at least 4 unknown extenders in that period - and ALL of them relapsers! - to get numbers worse than Ferenci's. I seriously doubt that :-)

[wyntre9]

Awwww.....

you guys are SAINTS for taking time to explain this stuff in a way that even I can (hopefully) understand.

Thanks so much for your help.

I know this topic has been addressed before but I didn't read through those threads (for some reason, maybe TIME)

But now that I'm halfwy through the 72 weeks and having a rough time i do need good reasons to continue (or not) beyond the SOC 48 and i appreciate the info you provided to help me with that decision.


Jm.

*lol* - Sleep number bed . . . yup.

GP - matching 'your' stats to 'study' stats.  

CW,

Good suggestion, about riba . . . I'm almost ready to consider it . . .

bill,

GL with spanish class.  Bet you'll be head of the class.  

wyntre

[Valtod]

Wyntre, my point was that the chances for SVR - if you go for 72 weeks - are pretty good and shouldn't be your main concern.

As I wrote to Drofi, the scary and almost unpredictable variable in the equation “Should I extend or not?” is actually the severity of the side effects during and post treatment and the possible long-term damages.

I'm already 10 days off Tx and my horrible rash started subduing during the weekend but yesterday it came back with vengeance. And I've been using strong cortisone cream (Lidex)... Why this flare-up? Am I going to get worse? Are these some autoimmune cycles that will torture me for life?

Other people complain about other long-term side effects, caused by extended or repeated treatments. You've probably seen the posts... I know a woman who achieved  SVR but developed AIH (autoimmune hepatitis) BECAUSE of the Tx. Now it destroys her liver at a much faster pace than the HCV ever did for 20 years. I think she's on the transplant list now.

Long-term SX do not happen to every extender and are not equally bad. But they do happen often enough to make you REALLY wonder: "Is the risk worth it?" Unfortunately, no studies, viral decay models and formulas will help you with this one. You have to listen to your own body (and hopefully an experienced hepatologist, who's not  in denial about the long-term SX).

Best wishes!

[Valtod]

Increasing Riba can really help.
Tapias - 800 mg RBV - only 44% SVR
Ferenci - 1000-1200 mg RBV - 77% SVR

However, increasing Riba is proved to work BEFORE reaching UND. Increasing it AFTER week 37 (when you're already on weight-based regime) doesn't make much sense.

Actually, I see you and I discussed the issue before too:
http://www.medhelp.org/posts/show/98287
Wyntre:
Is there any evidence that late responders can benefit from increased riba AFTER having reached UND and THEN continuing higher doses for the duration of TX?
----------------
Valtod:
No, there is no such evidence. Any induction approach or tweaking of dosage makes sense only in the beginning of Tx, especially the first couple of weeks. After having reached UND, dosage increase will not bring any benefit (but prolonging Tx duration will). Actually, reducing Peg and RBV to 80% can be safely done after week 36 (or week 48 in case of extened Tx).

Jim pointed out the Lindhal study where they seem to use the RBV as the muscle drug, instead of the PEG. But don't forget they used RBV in VERY high doses in carefully controlled environment and "patients were treated with erythropoietin and blood transfusions when indicated".

Jim himself couldn't tolerate high doses Riba. NYGirl almost ended up in a hospital because of such experiments. It's definitely not something to DIY at home.