jmjm treatment duration

[orleans]

Hey, Do you have the info on shortened treatment time in a form I could present to my Dr. (ie. abstracts of something) I mentioned the possibility of 24 weeks if I were to rvr and he didn't much care for that idea. thanks, jerry

[Mikkimoe]

Gauf - Yes, small world...pretty amazing he is your doctor. I'd love to find out what he thinks about it today - 4 years later. I would also love to get the entire article. We'll talk OK. Also I assume from reading your profile that I should ween myself off my anti-inflamitories as well? I have stopped them on the most part except when I am having a real bad day (every 3 days or so).

nygal - I totally agree with you on the SOC and going the distance. I am concerned a bit about the hepta manifistations that come with longer tx. I already have so many things wrong with me - I'd hate to end up with another condition after this is all ove - but I'd hate worse to still have this when it is over :-)

Jim - yep you've got a point there...would be great to find out more. Thanks

[jmjm530]

Yes, that's the study. But note that it's "2004" so one would think that if the results were verfied that entercept would have been incorporated into SOC, but it hasn't. At one point I thought about contacting the author to see if any follow-up, and if not, why. If you do, I'd be interested in any response you get back, as well as a peek at the full-text which the author might send you.

-- Jim

[Deb_c430]

Very well said,  I think there is often a danger here that we see only positive the what we want to see and are presented in facts in studies.

These studies are theories,  not set in stone sciences. I am not saying do not be positive,  I beleive that is as important as all the studies.  

We are all different.  

[jdwithhcv]

Well said!

[nygirl7]

Please remember a study is just a study and if you wanted to present something with certain terms to someone you could probably "prove" anything you wanted to on this earth to prove your point of view.

Relapse rates being so high already - just go in heads first and unless some great tragic side effect comes along that you just can't handle and you HAVE to stop early then stop at that date.

Seriously, there are so MANY people who have relapsed who did every single pill and shot and everything they could - who are just literally dying to get SVR...it's not worth taking the chance.

Go in, be positive and just do it right the first time. NO wonder your doctor is not hip at the idea it's NOT SOC for this disease.

[gauf]

Small  world, Dr. Nizar Zein is my hepatologist. He never mentioned etanercept to me though. Interesting report.

[Mikkimoe]

Yippi - I think I found it!  This was in 2004...but good results.
Is this the one you were refering to?

Etanercept as an adjuvant to interferon and ribavirin in treatment-naive patients with chronic hepatitis C virus infection: a phase 2 randomized, double-blind, placebo-controlled study☆

Nizar N. Zein, for the Etanercept Study Group†


Received 15 April 2004; received in revised form 12 October 2004; accepted 12 November 2004. published online 29 November 2004.

Background/Aims
Current therapies for patients with chronic hepatitis C virus (HCV) do not achieve sustained viral clearance in most patients, and are associated with severe toxic effects. Our aim was to investigate the efficacy and safety of etanercept as adjuvant to interferon and ribavirin in treatment-naive patients with HCV.

Methods
Double-blind, randomized, placebo controlled trial. Fifty patients with chronic HCV were randomly assigned to receive interferon alfa-2b and ribavirin with either etanercept or placebo for 24 weeks. The main outcome measure was the absence of HCV RNA at 24 weeks, the on treatment response at the end of the etanercept randomization period.

Results
At 24 weeks, HCV RNA was absent in 63% (12/19) etanercept patients compared to 32% (8/25) placebo patients (P=0.04). In addition, patients receiving etanercept had lower frequency of most adverse events categories compared to placebo.

Conclusions
Etanercept given for 24 weeks as adjuvant therapy to interferon and ribavirin significantly improved virologic response at the end of the etanercept randomization period among patients with HCV, and was associated with decreased incidence of most adverse effects associated with interferon and ribavirin.

[Mikkimoe]

Your're only stage 1 and remember the idea is to kill the virus, not the patient. This concept sometimes gets lost when we get into "warrior" mode on treatment.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Love it....thanks for the wake up call. Odds are on my side either way, I'll turn my panic button off for a while. Actually I think the zoloft did that for me. It's amazing how calm I have become in the last 2 weeks.

One last thing on the Enbrel/Peg relastionship - It was my impression that the Peg increased or stimulated the immune system to fight the virus whereas the Enbrel (TNF blocker) suppresses the immune system so it stops attacking the joints. But you mentioned that it may enhance SVR? I have to do some searching - it would be very interesting. It seems most folks with SRA have it post tx not pre so not much out there study wise - another **** shoot.

[jmjm530]

I'm not saying pay for every article, but if you're going to base an important tx decision in part on a study, often best to see full-text and not just the abstract -- whether you pay, get it in the library, etc, etc.

I was suggested Enbrel early-on in tx because of interferon-induced psoriasis.  I declined because I wanted to try light treatments instead, plus I already had enough of drugs and injections even at that early point in treatment. My research at the time showed that Enbrel at one time was trialed with Peg to enhance SVR, but don't believe that trial went anywhere. Still you could "Google" it. My tx doc said it was OK to take. It does appear to be very liver friendly.

Later in tx I asked the same question to a consulting liver specialist. His take was that mixing two immunosuppresives -- Enbrel and Peg -- could have unknown results. His recommendation therefore was not to use Enbrel unless I was forced to by the psoriasis.

I think that suggestion is most pertinent to your case. If stopping the Enbrel means "extreme pain and immobilization" then don't stop it.. Your're only stage 1 and remember the idea is to kill the virus, not the patient. This concept sometimes gets lost when we get into "warrior" mode on treatment. So, personally, I'd take the Enbrel, and take your chances. Maybe it will help, maybe hurt, maybe neutral in terms of SVR. I doubt anyone can really give you a definitive answer.  I really know nothing about Prednisone and how it might combine with both Enbrel and treatment. I'm sure others here have at least more experience with Prednisone.

-- Jim

[Mikkimoe]

Thanks for the great information...I'm glad I like to research, although I'm not real fond of paying for information that is probably public info somewhere. I had been to several of the sites you mentioned above but not others...I'll go exploring.

I have another question for you if you are OK with that...I have it posted on a dead thread somewhere. This is a tough one...
Here's my dilemma.... I am taking Enbrel for my severe RA (a TNF blocker) and prednisone. From what I understand they are immune suppressives. Since the HCV tx is an immune stimulant will they work together without contraindications? There have been no studies on this that I am aware of. My UCI doc believes it may be OK to do them both at once. I don't want to risk it not working. If I stop the enbrel I will be in extreme pain and immobile but will do it if I have a better chance to SVR. I can't stop the prednisone - been on it too many years.  Maybe I could taper the Enbrel. Instead of the 2 injections each week I could take 1 per week...I see Dr. Poordad at Cedar Sinai next week and will get his take on it but thought I'd gather as much info as possible before hand. What is your take on this?

[jmjm530]

Just to clarify a little. The implication from the liver specialist was that an additional 12 weeks at a tapered dose would be more effective than stopping treatment without the dose.

However, my read was not that it was the taper per say, that was beneficial, but just that there was more time on the inteferon.

BTW his actual suggestion was to stop at week 48 given I was RVR. The taper was more in response to some of the hypotheticals I presented to him in terms of treating beyond 48 weeks.

[jmjm530]

I'm sort of neutral as to tapering. I didn't do it when presented to me as an option way back then. Reason being I was RVR, figured I had an excellent shot at SVR, so why rock the boat with something unproven that in some strange and unexpected way might backfire? That said, maybe if I was a slow responder, I might have reasoned why not try something different. Also, looking back, I did have a very rough time of it coming off the Peg, and maybe tapering would have made a difference. Or maybe not.

But as to your specific question, I would think the most protective (of SVR) way to taper would be to taper at the end of the planned tx as opposed to somehow figuring in the taper as part of the treatment like you seem to be suggesting.

Actually, one very well known liver specialist did suggest that instead of extending to 60 weeks from 48 (that was a plan at one point in time) that I do some sort of taper (half dose, then quarter dose) for the additional 12 weeks. However, when I questioned him much later whether he thought I would have a better chance of SVR with 60 weeks at full-dose or 48 at full and 12 at a taper dose -- he said a better chance of SVR with 60 weeks at full dose.

Is he correct? Are others here correct when they hypothesize that somehow a taper will help prevent an immune "dead spot" at EOT where relapse may occur? These are all just theories as I see it. No one knows. Anyway, I ended up doing 54 weeks at full dose and stopped all at once. No taper. YMMV.

-- Jim

[orleans]

I know that you have not been a proponent of "tapering" at the end but what do you think about doing this from 24 weeks as a sort on comprmise? There will be Alinia. jerry

[jmjm530]

This might be helpful with the "advanced fibrosis/SVR" issue. You would then have to see how that relates to the above study.
http://www.hivandhepatitis.com/2006icr/ddw/docs/052306_e.html

[jmjm530]

Yes, that's what the abstract says, but what does it mean? Did the data come from stage 3's (which is considered advanced) or did they lump stage 3's with stage 4's as in many earlier studies, which tends to skew things.That's another reason to order the full-text and even contact the researchers for missing-link data such as might be the case with your question.

Related, there was a recent study that suggested that only stage 4 (not stage 3) was associated with less of a chance of SVR. But again, studies do vary, and it's important to closely look at all the fine points, and try to make the best matches possible.

-- Jim

[orleans]

Muchos gracias, Jim, the abst. you posted said "• The only predictive factor for SVR in patients with RVR was advanced liver fibrosis." Should I take this to mean that those with advanced fibrosis had  negitive predictors? Stage 3 = advanced fibrosis, No? thanks so much, jerry

[R Glass]

I met with my Gastro. He asked how I am handling the sx. I told him I believe I can make it even though some times it is hell. I told him my biggest concern is my job. I am a Commercial Construction Superintendent and I get paid to stay a step ahead of the game and head off potential problems. I can see myself loosing my edge daily. Forget staying a step ahead, I am struggling to stay in the game. He said, since I am 2b, was undetected at 4 weeks, I could stop at 16 weeks and my SVR rate would be 80%. I told him, Thanks for being honest but as for now stopping tx early is not an option. After going through all this and risking it all for 8 weeks, I would never forgive myself, if I didn’t make SVR.

[jmjm530]

Forgot to mention Medscape/Medline. You can research and order up articles there as well:

http://www.medscape.com/medscapetoday

http://tinyurl.com/2qj9vg

Also, if you are a student, or know a student, they often have free access to the full-text studies.

[jmjm530]

Yes, that's almost a two-log difference in only three weeks. Seems unusual like your doc said, but I'm not surprised given some of my pre-tx tests. Like from 150,000 to around 1.5 million  in a few months just prior to treatment.  Also, best to stick with the same lab for comparisons.

So if you say with Quest, maybe do your pre-tx test with Heptimax and continue with same test until you are at least UND. After that you could still stay with it or switch to a qualtiative. The same idea with LabCorp but picking the right tests are more complicated. But assuming your VL will be under 2 million pre-tx, you could use their HCV  NGI  quantasure quantitative, PCR LC#140639 (range 2-2 million IU/ml). This is a different test from their usual Quantasure Plus which is slightly less sensitive. In order to make sure you get  the more sensitive Quantasure, you must specifify the LC number of they may default you to the less sensitive Quantasure Plus. This is about as sensitive a test as you can get but the limitations are it only goes up to 2 million and their is a gap in the quantification between the very sensitive Qual they use and their Quant. This can make reading results a bit more confusing both to patient and even doctors.

You would have to check the specific studies to see how the categorized "low viral load" of if indeed every study even used that as a criteria. The details do count in these studies that's why best to order the full-text versions of any study you may be basing a treatment decision on.  I've seen full-text offered for a fee on Wiley, if I remember correctly. Pretty much anything can be ordered full-text for a fee somewhere on the net. The same articles can often be gotten for free from a local medical library or even by emailing the author with perhaps a little flattery :)

Some other worthwhile sites for research. Some require free registration.

http://www.clinicaloptions.com/ (some good clinical/treatment modules)
http://www.projectsinknowledge.com/
http://www.hivandhepatitis.com/ (check out their index of "all hcv articles by topics"
http://www.natap.org/
http://www.hcvadvocate.org/
http://www.janis7hepc.com/

[Mikkimoe]

Thanks for your advise. I am finding alot on http://www3.interscience.wiley.com. Is there better sources that I am missing?

Also I just took another VL last week - seems my last 2 had great disparities. The first one I took read 41,540. Three weeks later it was 3,730,000. They were different labs (Quest then Lab Corp) My Doc said that was unusual. Should be interesting to see what this one is 3 weeks later.

Assuming I start tx in 3 weeks what do you believe would be the best VL range to take the risk of a shorter tx?

[jmjm530]

The 9% figure -- weight-based dosing -- is the one I'm familiar with and think most pertinent. I've also seen other studies that suggest equal odds.

As CS suggests, you want to make sure you fit the patient profile of these studies. That means really studying up on as many of them as possible -- order the full-text, not just the abstracts -- and then presenting them to your doctor in some organized fashion for critique/debate/evaluation.

-- Jim

[CockSparrow]

Anyone considering shortening Tx should make sure they fit the profile of thoose most likely to repond.
The only subgroup to have acceptable SVR rates and low relapse rates (any Geno) is low viral load. In other words you need LVL and be RVR to benefit. RVR on it own has higher relapse rates.

CS

[Ironduke]

Here is another paper on the subject:

"Early indentification of HCV Genotype 1 patients responding to 24 weeks of Peginterferon alpha-2a (40 kd)/Ribaviran therapy"  Jensen et al, Hepatology Vol 43 No. 5 2006.

Good luck

Ironduke

[Mikkimoe]

I have to make this decission as well. My UCI doc has mentioned 16 weeks tx Peg+1000 rib.  I believe my VL may be rather high for a shorter tx @ 3,750,000.

Here are several 2b studies that may be relavant.
Basically they state 12 weeks as infereior by about 19% in the 1st study (only 800 rib). And the 14 week study was noninferior at about 9% W/varied rib doses.

Randomized comparison of 12 or 24 weeks of peginterferon  -2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection
Accepted Article Online: 1 Feb 2008
Copyright © 2008 American Association for the Study of Liver Diseases
Abstract
Previous trials investigating the efficacy of treatment durations shorter than the standard of 24 weeks for chronic hepatitis C virus (HCV) genotype 2/3 infections have yielded discordant results. The aims of this investigator-initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short-term therapy. Three hundred and eighty-two genotype 2/3 infected patients (ITT population) at 31 centers in Denmark, Finland, Norway, and Sweden were randomized to 12 or 24 weeks of peginterferon -2a 180 g/week plus ribavirin 800 mg/day. Twelve weeks of therapy was inferior to 24 weeks in the ITT population (SVR rates 59% vs. 78%, P<0.0001) and in the subgroups of patients infected with genotypes 2 (56% vs. 82%, p=0.006) or 3 (58% vs. 78%, p=0.0015). These differences were observed regardless of fibrosis stage. Age and HCV-RNA levels on days 7 and 29 were independent predictors of SVR. Short-term treatment was useful in patients <40 years especially if HCV-RNA was undetectable on day 29 and also in patients 40 years provided that HCV-RNA on day 7 was below 1,000 IU/mL in addition to being undetectable on day 29. If neither of these two criteria were met for patients 40 years, 24 weeks of therapy was superior (p<0.0001). In conclusion, peginterferon/ribavirin treatment for 12 weeks in HCV genotype 2/3 infection is overall inferior to 24 weeks, but may be useful in some patients with a rapid initial clearance of virus. (HEPATOLOGY 2008.)

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Received: 27 August 2007; Revised: 21 December 2007; Accepted: 23 January 2008


Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response

Published Online: 1 Nov 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Abstract  - Nov 2007
A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA-positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon -2b (1.5 g/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, -0.1 to +13.9). Conclusion: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks. (HEPATOLOGY 2007.)

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Received: 14 May 2007; Accepted: 10 August 2007
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