Aa
24 WK TREATMENT FOR EVR AT 4 WKS
Hello Everyone....
I was negative at 4 weeks. Latest research shows 89% SVR at 24 weeks for 4 week early responders, same as 48 weeks for genotype 1b. As a result, due to numerous side effects, including dangerously low white blood cell count, I am considering discontinuing at 24 weeks. I just took 12 week medical leave due to side effects. Any thoughts?
I was negative at 4 weeks. Latest research shows 89% SVR at 24 weeks for 4 week early responders, same as 48 weeks for genotype 1b. As a result, due to numerous side effects, including dangerously low white blood cell count, I am considering discontinuing at 24 weeks. I just took 12 week medical leave due to side effects. Any thoughts?
Thanks for input. Its beginning to look like a no-brainer to me. If I gain no advantage by going to 48, why torture myself for an additional six months. I think its worth a try. I'll let you know how it goes.
Goofy's comment is correct. The statistical analysis in Jensen focused primarily on identifying the factors shared among the 51 patients who achieved RVR among the 216 patients assigned to the 24 week arm of that study. They found that low baseline vl, less fibrosis and subtype 1b were predictive of RVR.
They also report some minimal analysis of the factors predictive of SVR among that group, which obviously is what you are interested in but this is limited to two effects. Those who achieved RVR were *much* more likely to SVR (89% vs 19%) and you already know this. Also, those on 1000/1200 riba were slightly more likely to get an und at EOT than those who did 800 (97% vs 94%) but this advantage washed out by 6 months post tx since the SVR rates were nearly identical 89% vs 88%.
The RVRs who went on to 48 weeks didn't have SVR outcomes that were any better than those of the 24-week short-timers but bizzarely, they showed a greater difference between the high/low riba groups (73% vs 91%). I didn't see a significance calculation for this in the paper but presumably it's NS( it would be pretty scary to conclude that, as an RVR, if you do continue for 48 weeks you've got to stay on the high riba or risk actually lowering your SVR odds...).
Two quotes in Jensen refer to other studies.
<em>
"A retrospective analysis of data from patients treated with peginterferon -2a (40 kd) plus ribavirin for 48 weeks in a randomized, multinational, phase III study demonstrated that 91% of genotype 1 patients who became HCV RNA-negative by week 4 had a SVR compared with 48% or fewer of those who did not become HCV RNA-negative until week 24" </em> refers to <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=PubMed&doptcmdl=citation&term=J+HEPATOL%5Bta%5D+AND+43%5Bvi%5D+AND+425%5Bpg%5D">Ferenci et al '05</a> and
<em>"In the TeraViC-4 study, patients with detectable HCV RNA at week 4 were randomized to either 48 or 72 weeks of treatment with peginterferon -2a (40 kd) plus ribavirin 800 mg/d. SVR rates in patients who did not achieve a RVR were significantly higher in the 72-week versus the 48-week treatment groups, primarily because of a reduced rate of virological relapse during follow-up.[8] Conversely, the overall SVR rate in genotype 1 patients with a baseline HCV RNA level of 800,000 IU/mL or less who had a RVR at week 4 was 76% after 24 or 48 weeks of treatment." </em> refers to TERAVIC abstract I mentioned above.
All in all, though Jensen (89%) Zeuzem'06 (89%) TERAVIC(76%) and Ferenci(91%) differ somewhat in their estimate of the SVR odds for RVRs, those that compared 24 vs 48 (all but Ferenci) found no benefit to the extra time.
One other interesting point is that the reason for the good agreement between the Jensen and Hanziyannis estimates for the benefit of 48 vs 24 for non RVRs is simply that they're based on the same data (duhh...). The Jensen study is simply a retrospective analysis of the earlier data. All RVRs who needlessly suffered through 6 extra months of tx simply because this study data was not available for public analysis should feel free to yell a few choice obscenities.
They also report some minimal analysis of the factors predictive of SVR among that group, which obviously is what you are interested in but this is limited to two effects. Those who achieved RVR were *much* more likely to SVR (89% vs 19%) and you already know this. Also, those on 1000/1200 riba were slightly more likely to get an und at EOT than those who did 800 (97% vs 94%) but this advantage washed out by 6 months post tx since the SVR rates were nearly identical 89% vs 88%.
The RVRs who went on to 48 weeks didn't have SVR outcomes that were any better than those of the 24-week short-timers but bizzarely, they showed a greater difference between the high/low riba groups (73% vs 91%). I didn't see a significance calculation for this in the paper but presumably it's NS( it would be pretty scary to conclude that, as an RVR, if you do continue for 48 weeks you've got to stay on the high riba or risk actually lowering your SVR odds...).
Two quotes in Jensen refer to other studies.
<em>
"A retrospective analysis of data from patients treated with peginterferon -2a (40 kd) plus ribavirin for 48 weeks in a randomized, multinational, phase III study demonstrated that 91% of genotype 1 patients who became HCV RNA-negative by week 4 had a SVR compared with 48% or fewer of those who did not become HCV RNA-negative until week 24" </em> refers to <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=PubMed&doptcmdl=citation&term=J+HEPATOL%5Bta%5D+AND+43%5Bvi%5D+AND+425%5Bpg%5D">Ferenci et al '05</a> and
<em>"In the TeraViC-4 study, patients with detectable HCV RNA at week 4 were randomized to either 48 or 72 weeks of treatment with peginterferon -2a (40 kd) plus ribavirin 800 mg/d. SVR rates in patients who did not achieve a RVR were significantly higher in the 72-week versus the 48-week treatment groups, primarily because of a reduced rate of virological relapse during follow-up.[8] Conversely, the overall SVR rate in genotype 1 patients with a baseline HCV RNA level of 800,000 IU/mL or less who had a RVR at week 4 was 76% after 24 or 48 weeks of treatment." </em> refers to TERAVIC abstract I mentioned above.
All in all, though Jensen (89%) Zeuzem'06 (89%) TERAVIC(76%) and Ferenci(91%) differ somewhat in their estimate of the SVR odds for RVRs, those that compared 24 vs 48 (all but Ferenci) found no benefit to the extra time.
One other interesting point is that the reason for the good agreement between the Jensen and Hanziyannis estimates for the benefit of 48 vs 24 for non RVRs is simply that they're based on the same data (duhh...). The Jensen study is simply a retrospective analysis of the earlier data. All RVRs who needlessly suffered through 6 extra months of tx simply because this study data was not available for public analysis should feel free to yell a few choice obscenities.
I say go for the 24 weeks. Like you said if need be you got time. Best of luck to you
I was 409,884 pre treatment, 637 at wk 2 and -29 at wk 4. I am 51, stage 2. I am what the April 06 study I read calls a "superresponder". I cannot work on this stuff. The meds are not exactly complimentary to multi-tasking. I am single head of household and cannot afford to lose my job. I am currently taking my FEMLA leave. I could give it a shot at 24, go back to work and pray. I honestly don't think I can make it to 48 with the blood situation being what it is. I may be involuntarily terminated and am just hoping to get to 24 at this point. If it doesn't work, I have time to re-treat. It is my feeling that the protocols will be changed very soon for RVRs at 4 wks. And, yes, the low viral load is predicative of all RVR, EVR and SVR.
RVR says: I meet all of the criteria predictive of SVR at 24 weeks. ---------------------------------------
The last thing you might want to consider is your age and stage of liver damage. If you're under 50 and little or no liver damage, then you might reasonable go for the 24-week short course. Should you relapse, time is on your side in terms of re-treating.
On the other hand, if you're older and have significant fibrosis (stage 3 or 4), then taking the more conservative approach (48 weeks) might make more sense as relapse has more consequences.
I became non-detectible at six weeks but was under 50 IU/ml at 4 weeks. But because of my age (59) and liver damage (stage 3) my doc wanted me to extend to 54 weeks. And while my VL was 1.5 million as opposed to < 600,000, my doc (who is aware of the study) would not have stopped me at 24 weeks. So while these studies are exciting, they still may not apply to all -- even those meeting the stated criteria. It's also unclear -- at least from the abstracts -- how representative of the treatment population the study participants are in terms of age, histology,
etc.
All the best luck in your decision and please keep us posted.
-- Jim
The last thing you might want to consider is your age and stage of liver damage. If you're under 50 and little or no liver damage, then you might reasonable go for the 24-week short course. Should you relapse, time is on your side in terms of re-treating.
On the other hand, if you're older and have significant fibrosis (stage 3 or 4), then taking the more conservative approach (48 weeks) might make more sense as relapse has more consequences.
I became non-detectible at six weeks but was under 50 IU/ml at 4 weeks. But because of my age (59) and liver damage (stage 3) my doc wanted me to extend to 54 weeks. And while my VL was 1.5 million as opposed to < 600,000, my doc (who is aware of the study) would not have stopped me at 24 weeks. So while these studies are exciting, they still may not apply to all -- even those meeting the stated criteria. It's also unclear -- at least from the abstracts -- how representative of the treatment population the study participants are in terms of age, histology,
etc.
All the best luck in your decision and please keep us posted.
-- Jim
A quick glance at the Jensen abstract and it looks to me like the 89% applies to all RVRs. Predictive value of genotype seems to apply to acheiving RVR. VL was reported as redictive of RVR and SVR, but the 89% seems to hold up regardless of VL (for RVRs). Am I reading it wrong?
the other study worth trying to dig up is the full data for the TERAVIC study. This is usually cited in the context of 48 vs 72, however one arm of that study also compared 24 vs 48 for RVRs. The only link I can put my hands on is the old '04 <a href="http://www.natap.org/2004/EASL/easl_06.htm"> '04 conference abstract</a> which, to my reading is not sufficiently clear about the outcome of the 184 RVRs by genotype (they seem to lump all subtypes together). The TERAVIC data is supposed to have been published in the April Gastroenterology, per the citation in the <a href="http://www.gastrojournal.org/article/PIIS0016508506004719/fulltext">Fontana editorial </a> in that issue. However, it's not there nor is it in their "in press" list. Perhaps someone else can find it. However, between the recent Jensen and Zeuzem studies and the older TERAVIC, you've got a lot of data to guide your decision. All the best.
oh. bad news then huh? Or not as good news as I thought? How long did it take for you to relapse?
Didn't mean to stir up for you. Recently we've had a rash (no pun intended) of 3's who have relapsed. I finished 24 wks in December and found out about the relapse in April. One theory is that my liver damage had something to do with it. Although I did get undetectable at 12 weeks it appears that tx should have been longer and stronger. Kalio also replapsed but jumped back into tx within 2 weeks of her completed 24. So 3a's are in iffy situations. And there are others. Hopefully you have a doc who is experienced with lot of hcv patients and who recognizes some of the sublte differnces that may be needed in tx protocols. But, first is the decision to treat or to wait.
What about the lump? Did this doc see it, feel it, rub it?
What about the lump? Did this doc see it, feel it, rub it?
you probably want to read <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16628671&query_hl=9&itool=pubmed_docsum">Jensen et al 06</a> and <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed">Zeuzem et al '06</a> along with the accompanying editorials by <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16628667&query_hl=13&itool=pubmed_docsum">Davis'06</a> and <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16293337&itool=pubmed_docsum">Craxi and Camma'06</a> before making a final decision. Note in particular that per the Jensen study, there is a correlation between high VL (either >20000 or >600000) and subtype (1a vs 1b). These are new results and the direction is not yet clear. The Craxi editorial is cautious in its interpretation, in part because of the design of the Zeuzem study:
<em>"At the present time, the strength of the evidence presented by Zeuzem and co-workers is in our opinion not sufficient to generalize the applicability of this approach to optimization. While further randomized trials are in progress, subjects with genotype 1, a low viral load and an early drop of HCV-RNA under therapy may be treated with this short schedule if they have modest or no fibrosis and hence are unlikely to progress significantly should HCV relapse. Those with more advanced fibrosis are probably still better served by the conventional, more troublesome schedule of 48 weeks. "</a>
Davis, who was also a proponent of the 12 week EVR rule, is als cautiously optimistic :
<em>"Are we ready to use RVR in our clinical practices and modify the standard of care? Probably not quite yet. Some physicians who are comfortable with the nuances of treatment may wish to integrate RVR into their treatment armamentarium, but the applicability to other patient groups must be shown before this becomes common practice. I believe that shorter treatment for those with RVR will be increasingly accepted over time. We can be certain of one thing one size no longer fits all."</em>.
All this caution is nice for the Drs, but you're the one doing tx and interested primarily in a sample of size 1. IMHO, if you're an RVR who's having a lot of trouble, the extra 6 months is not worth it.
It's also interesting that, independently of RVR, the Jensen study reported exactly the same improvement in SVR for doing the extra 6 months from 24 to 48 as the older <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14996676&query_hl=21&itool=pubmed_docsum">Hadziyannis</a> clinical trial data used to set the current standard of care : from 42% to 52% per Jensen vs 41% to 51% per the older study. That's the kind of consistency that makes stat hounds feel warm and fuzzy all over.
<em>"At the present time, the strength of the evidence presented by Zeuzem and co-workers is in our opinion not sufficient to generalize the applicability of this approach to optimization. While further randomized trials are in progress, subjects with genotype 1, a low viral load and an early drop of HCV-RNA under therapy may be treated with this short schedule if they have modest or no fibrosis and hence are unlikely to progress significantly should HCV relapse. Those with more advanced fibrosis are probably still better served by the conventional, more troublesome schedule of 48 weeks. "</a>
Davis, who was also a proponent of the 12 week EVR rule, is als cautiously optimistic :
<em>"Are we ready to use RVR in our clinical practices and modify the standard of care? Probably not quite yet. Some physicians who are comfortable with the nuances of treatment may wish to integrate RVR into their treatment armamentarium, but the applicability to other patient groups must be shown before this becomes common practice. I believe that shorter treatment for those with RVR will be increasingly accepted over time. We can be certain of one thing one size no longer fits all."</em>.
All this caution is nice for the Drs, but you're the one doing tx and interested primarily in a sample of size 1. IMHO, if you're an RVR who's having a lot of trouble, the extra 6 months is not worth it.
It's also interesting that, independently of RVR, the Jensen study reported exactly the same improvement in SVR for doing the extra 6 months from 24 to 48 as the older <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14996676&query_hl=21&itool=pubmed_docsum">Hadziyannis</a> clinical trial data used to set the current standard of care : from 42% to 52% per Jensen vs 41% to 51% per the older study. That's the kind of consistency that makes stat hounds feel warm and fuzzy all over.
Here's that <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16290907&query_hl=24&itool=pubmed_docsum">Zeuzem et al '06</a> link again.
I tell you - with all of the relapses that we see it makes more sense to EXTEND treatment as a 1B rather than shorten the course. Being clear at week 4 in no way guarantees that you are in FACT REALLY clear...the virus that hides out inside other places really does want to grow back big time - and will if let it.
I've been struggling lately because as a 1A and 1B and I should treat for an ADDITIONAL 34 weeks (to 72 weeks) but I don't want to.
As a 1B which is the HARDEST VIRUS TO KILL OF THEM ALL I WOULD NOT THINK OF TREATING FOR LESS THAN 48. NOT IN A MILLION YEARS.
It's nice to be clear...but killing off the residual virus that live inside us but are undetectible is too crucial to not try.
Considering the people who are SUPPOSED to treat for 24 weeks because they have the "EASY" virus(2 and 3s) are relapsing all over the place - I can't see why any doctor would really ever ADVISE the hardest virus to treat for the same amount of time.
To me it makes no sense.
But...maybe I just LOVE being on tx so much I can't stop! ;)
I've been struggling lately because as a 1A and 1B and I should treat for an ADDITIONAL 34 weeks (to 72 weeks) but I don't want to.
As a 1B which is the HARDEST VIRUS TO KILL OF THEM ALL I WOULD NOT THINK OF TREATING FOR LESS THAN 48. NOT IN A MILLION YEARS.
It's nice to be clear...but killing off the residual virus that live inside us but are undetectible is too crucial to not try.
Considering the people who are SUPPOSED to treat for 24 weeks because they have the "EASY" virus(2 and 3s) are relapsing all over the place - I can't see why any doctor would really ever ADVISE the hardest virus to treat for the same amount of time.
To me it makes no sense.
But...maybe I just LOVE being on tx so much I can't stop! ;)
52Tele, Austin, of course! Where else would I get to see such great live music. Last 3 years ago when I lived near Auditorium Shores I could hear Willie Nelson from my porch! Tom Petty is playing Austin City Limits Festival this year. No other place to be but here. Plus it seems like there is a large HCV community here from the number of patients my doc sees. Although NYGirls #2 rated Doc sounds pretty good in ny. im jealous.
FLGuy, yea..the lump. Could be Steatosis or Fatty liver from mass drinking binges that was never able to heal because of the hep. I read somewhere that 3's commonly have Fatty liver. Doc rubbed around but said could be a lot of things and it is definately swollen but that could be just par for the course.
He said Biopsy is the only way to find out. I go in for that fun action in a few weeks.
From what I have been reading there are lots of factors that help tx along. From liver, to gender, to age, etc. But it seems the only way is to go into it head on.
All I know is that I am completely inspired by young ladies like NYgirl who are on the front lines of this stuff and fighting it daily head on. And the rest of you guys have completely saved me from the depths of dispair... and abdomen rubbing...
FLGuy, yea..the lump. Could be Steatosis or Fatty liver from mass drinking binges that was never able to heal because of the hep. I read somewhere that 3's commonly have Fatty liver. Doc rubbed around but said could be a lot of things and it is definately swollen but that could be just par for the course.
He said Biopsy is the only way to find out. I go in for that fun action in a few weeks.
From what I have been reading there are lots of factors that help tx along. From liver, to gender, to age, etc. But it seems the only way is to go into it head on.
All I know is that I am completely inspired by young ladies like NYgirl who are on the front lines of this stuff and fighting it daily head on. And the rest of you guys have completely saved me from the depths of dispair... and abdomen rubbing...
What about that lump?
Having 3 is better than 1 but not as good as geno 2. But, that's come from a 3a that recently relapsed. Many 3's tx for 24 weeks, although new doc's office say that they now treat 3's as a standard 48 weeks like geno 1's.
Having 3 is better than 1 but not as good as geno 2. But, that's come from a 3a that recently relapsed. Many 3's tx for 24 weeks, although new doc's office say that they now treat 3's as a standard 48 weeks like geno 1's.
Listening to Willie and a few frosty long necks seem to go together. But, other matters to deal with first. Good luck on the bx, it's not so bad. I'd rather have a bx than the colonoscopy I'm getting on Monday.
Honestly, I think you should stick with it. You are halfway there!
I am 24 weeks into treatment, 1b and clear. The thought of stopping this treatment now and then having to do it again is enough to keep my resolve strong enough for 24 more weeks.
Hang in there.
I am 24 weeks into treatment, 1b and clear. The thought of stopping this treatment now and then having to do it again is enough to keep my resolve strong enough for 24 more weeks.
Hang in there.
Thank you for your comments. What I read were Conference Reports for NATAP at www.natap.org. One dated 11/11/05, another dated 4/27/06. What stuck with me is this, "Overall, 89% of patients with an RVR treated for only 24 weeks achieved an SVR. Moreover, patients with an RVR treated for 48 weeks did not obtain a better SVR rate. Lower baseline viral load and 1b did better than 1a.
Let us know how it goes. I'll be waiting to hear what he puts on the card with the roses. I guess you'll want to dress nice, but nothing that will get too wrinkled :)
Maybe this is what you're basing your decision on:
http://www.hivandhepatitis.com/hep_c/news/2005/ad/100705_a.html
If so, keep a few things in mind:
(1) The 89% SVR figure you quote is only for those with non-detectible virus at week 4 AND who had pre-tx viral loads of less than 600,000 IU/ml.
(2) This study was done with Peg Intron. Maybe other studies were done with Pegasys, not sure, but some geno 2 studies suggest there may be a difference in treatment lengths between the two pegs when going short course with Pegasys possibly requiring some xtra weeks.
(3) When you say you're negative at 4 weeks, what is the sensitivity of the test you used? I'd compare your test sensitivity against the one used in the study. For example, if your test has a sensitivity of only 600 IU/ml and the study used a sensitivity of 50 IU/ml, then you're comparing apples to oranges. I don't know what test sensitivity the study used but if you order the up the full-text version it would probably be include.
All the best moving forward.
-- Jim
http://www.hivandhepatitis.com/hep_c/news/2005/ad/100705_a.html
If so, keep a few things in mind:
(1) The 89% SVR figure you quote is only for those with non-detectible virus at week 4 AND who had pre-tx viral loads of less than 600,000 IU/ml.
(2) This study was done with Peg Intron. Maybe other studies were done with Pegasys, not sure, but some geno 2 studies suggest there may be a difference in treatment lengths between the two pegs when going short course with Pegasys possibly requiring some xtra weeks.
(3) When you say you're negative at 4 weeks, what is the sensitivity of the test you used? I'd compare your test sensitivity against the one used in the study. For example, if your test has a sensitivity of only 600 IU/ml and the study used a sensitivity of 50 IU/ml, then you're comparing apples to oranges. I don't know what test sensitivity the study used but if you order the up the full-text version it would probably be include.
All the best moving forward.
-- Jim
the natap summaries are based on the studies reported in the two journal articles, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16628671&query_hl=9&itool=pubmed_docsum">Jensen</a> and <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16290907&query_hl=24&itool=pubmed_docsum"Zeuzem</a>.
Before making such an important decision it's probably worth going through the actual articles and discussing them with your Dr. The Jensen data used a 50 iu test and ifn-2a (roche/pegasys). Zeuzem used 29 iu sensitivity and ifn-2b (schering/pegintron). Zeuzem only considered patients with baseline VL <600,000, Jensen did not screen on VL but found that VL <600,000 was a significant predictor. Jensen also found that 1a vs 1b was a factor, with 1bs doing better, and that for the 1as a viral load under 200,000 was predictive. If you meet all the above checklists (1b and <600,000 at start or 1a and <200,000 plus week 4 VL < 29) the above data supports that promising 89% outlook.
Before making such an important decision it's probably worth going through the actual articles and discussing them with your Dr. The Jensen data used a 50 iu test and ifn-2a (roche/pegasys). Zeuzem used 29 iu sensitivity and ifn-2b (schering/pegintron). Zeuzem only considered patients with baseline VL <600,000, Jensen did not screen on VL but found that VL <600,000 was a significant predictor. Jensen also found that 1a vs 1b was a factor, with 1bs doing better, and that for the 1as a viral load under 200,000 was predictive. If you meet all the above checklists (1b and <600,000 at start or 1a and <200,000 plus week 4 VL < 29) the above data supports that promising 89% outlook.
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
