24 Weeks for Selected Geno 1's.

http://tinyurl.com/c8kus

So..let's see I'm on week 22 of 48 or maybe 72 or maybe 96 ... but wait...maybe I really only have two weeks left. PLEASE MAKE THIS TRUE. LOL.

It does get confusing with all these studies, but the one trend that keeps appearing is that EVR is a very important guide both to treatment length and odds of SVR.

Just wish they broke the study out to take into consideration other variables like age, biopsy stage, etc.  Maybe I'll write and ask if they have the data.

For those who don't want to read the entire study, the 24-week recommendation is only for those geno 1's with undectable virus at week 4 and with low pre-treatment viral loads (<600,000). In this sub-group, with 24 weeks of treatment, the SVR was a very impressive 92%. The drugs used were Peg Intron and Riba.

[jmjm530]

REBETOL(R) Combination Therapy For Certain Hepatitis C Patients With Genotype 1 and Low Viral Load

KENILWORTH, N.J., July 29 /PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE: SGP) today reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has issued a positive opinion recommending approval of revised dosing instructions which allow a shorter, 24-week course of weight-based PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800 - 1,200 mg) daily combination therapy among a subgroup of patients with hepatitis C virus (HCV) genotype 1 infection and low viral load (< 600,000 IU/ml). A shorter 24-week course of therapy can be considered for these patients who have achieved rapid virologic response, defined as undetectable virus (HCV-RNA negative) at week 4 of treatment that is maintained through week 24. A 92 percent sustained virologic response was achieved with 24 weeks of treatment among the 41 percent of patients who met the criteria for early response.

PEGINTRON and REBETOL combination therapy was previously approved in the EU for a 48-week course of therapy for all patients with genotype 1 who exhibit virological response at week 12. Approval of this shorter PEGINTRON and REBETOL combination treatment regimen cuts by half the duration of therapy for a subset of hepatitis C patients with genotype 1 and low viral load. This is the only treatment regimen approved in the European Union (EU) for a 24-week course of therapy in certain genotype 1 patients.

The CHMP recommendation serves as the basis for a European Commission approval of this labeling change. A Commission Decision will result in Marketing Authorization with unified labeling that will be valid in the current EU 25 member states as well as in Iceland and Norway.

"The important results of this clinical study with PEGINTRON and REBETOL reflect the ongoing efforts of Schering-Plough to define optimal dose and treatment schedules for specific HCV patient groups," said Robert J. Spiegel, M.D., chief medical officer and senior vice president of medical affairs, Schering-Plough Research Institute.

Study Results

The recommended labeling change for PEGINTRON and REBETOL is based on results of a clinical study involving 235 patients with HCV genotype 1 and low viral load who received 24 weeks of combination therapy with weight-based PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800 - 1,400 mg daily); only two patients weighing >105 kg received the 1,400 mg dose). In the study, 41 percent of patients (97/235) had undetectable plasma HCV-RNA levels at week 4 and week 24 of therapy. Patients in this subgroup achieved a 92 percent (89/97) rate of sustained virological response (SVR). The high sustained response rate in this group of patients was identified in an interim analysis and prospectively confirmed.

Genotype 1 virus is the most common worldwide, the most difficult to treat successfully and accounts for about 70 percent of HCV infections among European patients overall, varying by geography. For patients with HCV genotypes 2 or 3, the EU labeling for PEGINTRON recommends that all patients be treated for 24 weeks. Patients infected with HCV genotype 4 are considered harder to treat and generally 48 weeks of therapy is recommended.

About PEGINTRON and REBETOL Combination Therapy

PEGINTRON and REBETOL combination therapy for chronic hepatitis C was approved in the European Union (EU) in March 2001. The recommended dose in the EU for combination therapy is PEGINTRON 1.5 mcg/kg/once weekly plus REBETOL 800-1,200 mg daily, adjusted to body weight. PEGINTRON had previously received centralized marketing authorization in the EU and is marketed as a monotherapy in cases of intolerance or contraindication to ribavirin for the treatment of adult patients with chronic hepatitis C.

PEGINTRON, recombinant interferon alfa-2b linked to a 12,000 dalton polyethylene glycol (PEG) molecule, is a once-weekly therapy dosed according to patient body weight that is designed to achieve an effective balance between antiviral activity and elimination half-life. REBETOL is an oral formulation of ribavirin, a synthetic nucleoside analog with broad-spectrum antiviral activity.

Chronic hepatitis C is estimated to affect more than 10 million people in major world markets, including 5 million in Europe. It is a leading cause of chronic liver disease and one of the most common reasons for liver transplant in Europe.

Important Information Regarding U.S. Labeling for PEG-INTRON and REBETOL

WARNING

Alpha interferons, including PEG-INTRON, cause or aggravate fatal or life- threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping PEG-INTRON therapy.

Ribavirin causes hemolytic anemia. Anemia associated with REBETOL therapy may exacerbate cardiac disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with REBETOL. It is advised that complete blood counts (CBC) be obtained at baseline and at weeks 2 and 4 of therapy or more frequently if clinically indicated.

REBETOL and combination REBETOL/PEG-INTRON therapy must not be used by women, or male partners of women, who are or may become pregnant during therapy and during the 6 months after stopping therapy. REBETOL and combination REBETOL/PEG-INTRON therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use effective contraception (at least two reliable forms) during treatment and during the 6- month post-treatment follow-up period. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of REBETOL. If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment stops, physicians are encouraged to report such cases by calling [phone].

[jmjm530]

The study conclusion has a number of interesing implications for treatment strategy.

Many geno 1's with little liver damage (stage 0 or 1) have chosen not to treat now and adopt a wait and see attitude. It's a  valid choice in my opinion, because of the 48 weeks of treatment required with only around a 50% chance of success.

But this new study suggests that in certain geno 1 populations, both treatment length and rate of success (92%) is similar (actually better) than with geno 2's.

So...one strategy for stage 0 or 1 geno 1's with low pre-treatment viral loads (<600,000) would be to treat with a week #4 PCR.

If the virus is undectable at week #4,then continue on for the 24 week course. Accoring to the study your chances are of success are 92%. Howeer if virus is detectable at week #4, then stop treatment, re-biopsy in 3-5 years, and hopefully by then there will be better treatments around.

[carpedi]

Do you know if Roche has had the same results with Pegasys and Copeg? I think I remember that most studies comparing the two don't find much difference between them. It would be so great if you only had to do the 24!!!!( And that's hard enough!)

[Tonyz]

<img src="http://www.geocities.com/tzeazas/Clipart.gif"/>

<font size="2" color="#336666">That would be so much more achevable...24 VS 72..
I hope there studies correct.I glad there is some more good news for you 1's.</font>

                 Blessings
                  TonyZ

[jmjm530]

Carp...I agree that the two drugs seem to perform the same but if I were just starting treatment and  a geno 1 with low viral load, I'd probably give Peg Intron a second look.

Tony...Yes! Yes! Yes!  24 weeks is so much more workable and achievable than 48 and/or 72 weeks. Hopefully, it will draw more people into treatment who fit this very specific profile.

But keep in mind, this study suggests 24 weeks only for a very specfic patient population.

So, in my case, for example, the 24 weeks (versus 48 or 72) is unfortunately just a day dream. LOL.

First, my pre-treatment viral load was 1.2 million. Second, while I was close to clearing the virus at week #4 (53) I didn't clear until week #6.

And most important, I'm a stage 3, which is known to have a higher relapse rate. So, until a study comes along with good stats on stage 3's, then it's 48 or 72 weeks for me.

[jmjm530]

Nice animated graphic! Do you have a list of HTML tags that work on this web site? For example, if we want to post a link or a a photo.
Thanks.

-- Jim

[friole]

That is astounding news.  I am like you - too high of a viral load (1.52mil) but it gives me pause.  After my 4th shot next Friday, I am definitley pushing for a PCR (which the GI says he normally does not do at 4).

You are right.  It would be such an incentive to get more people into treatment.  You know, Rifleman who is a 3 or 4 said that his doc is only treating for 12 weeks since he cleared at 4.  I had not heard of that short of a treatment before.

Yeah, Tony is good with the html!
Kathy

[Tallblonde]

Boy, with a viral load of only 714 IU/mL and Stage 0-1, this really gives me something to think about. A 92% chance of success?!! Wow!  Thanks for sharing this information.

Susan

[honey1616]

That would be a skip in the park for 1's!  Great News Jim!  However,,I won't beat myself over the head after finishing 52 LONG weeks,,,,as I started with 8 mil viral load so I'm sure I needed every bit of what I did to kick it out!

[cuteus]

the study was posted a while back by snookman, and the ensuing discussion is probably in archives.  they mention svr 92% but do not state how long post tx was that test?
I have seen many people here post EVR and still relapse after 48 wks, it is a gamble I would not take.
Cindee comes to mind, and Scott, weren't you EVR?  Too early to embrace 24wks for geno 1.

[Tallblonde]

This news, along with the recent nationwide ad campaign that was discussed in a thread below, really makes me wonder if Schering-Plough and Roche recognize that their glory days are numbered as better treatments are about to make their debut.  

It seems like they're now trying to drum up more business before the curtain falls on their products.  It's taken them THIS long to make a major discovery on dosage requirements for 1's with low VL's?  Or did they suspect it long before this but had no economic incentive to investigate it further?

Just curious jmjm.....if you were in my shoes, would you go for this opportunity, or still wait for something better?  Again, thank you for posting this important information.

Susan

[rifleman]

I was a 2b and had RVR.  I have the option to try my luck at 12 weeks.  Maybe I will, maybe I won't.  I can tell you that it feels GREAT to be rid of this virus.  All the nagging little joint aches and fatigue and occasional RUQ discomfort are gone.  Haven't had a smoke for 7 weeks (nor a drink) and have lost 15 lbs.  Currently 6'0" and 190 lbs.
One thing I'd like to see is a study on the long-term efects of peg and riba.  The stuff is absolutely toxic and it seems to me that less is better in that sense.
Of course, there is the personal genetic factor as well.  If you are a type 1 and are clear at 4 weeks, & I don't care WHAT your starting vl was, it is pretty much an indicator that you will be fine and SVR.
DJL

[omyst]

This is another study with genotype 1 that correlates EVR and SVR but without taking pre-tx viral load into consideration.

http://www.hivandhepatitis.com/2005icr/ddw2005/docs/hcv_052305_b.html

I cleared at week 4 (less than 10), but pre-tx viral load was 1,1 million and am a genotype 4. I would love to stop at week 24, but must aim for the full 48.

[rifleman]

I saw your post & my opinion is that, if I were you with your minimal liver damage, I'd wait for something better and keep tabs on your liver enzymes and vl. You have a very low vl.  I had a vl of 1,330,000.  That's a lot.  24 weeks of peg and riba is no picnic, either.  Maybe it's better than 48, but it still sucks.
DJL

[jmjm530]

Cuteus,

I believe "SVR" has a universal definition among researchers as virus-free, 6-months post treatment. What is "virus free" varies from group to group (in Europe it is often <50) but the 6 month period always seems constant.

That said, the 92% SVR number is the highest I've seen among RVR studies. Usually closer to geno 2 figures (80-85%) which isn't bad either. I'm dying to find out how many, if any, stage 3 and 4's were in the study. It's really an annoyance that they don't make those type of stats available.

Susan,

If you asked me before this study, I'd say hold off and wait for something better down the pike. But the new study does give pause. And the study is not in isolation. Many studies have shown EVR and especially RVR as stronger indicators of SVR. This study just quantifies it in terms of treatment length.

The plan then would be to get a PCR (with at least the same sensitivity as the study group used -- this is important) at week #4. If you're undectable, do another 20 weeks. If you are detectable, stop treatment and wait for something better down the pike. In a sense, you're investing four weeks time to help determine your odds for SVR.

Would I do it if I were in your shoes? Very close call. Keep in mind I've known I've had some type of chronic hepatitis since 1969. So living and waiting another 3-4 years with the virus is no big deal for me. However, I can understand why someone with little or no liver damage might want to get rid of the virus now, especially if they only had to treat for 24 weeks and they knew the odds for SVR would be 92%.

So my answer is I'd probably be tempted to try the the short treatment plan but I'm not 100% sure if I'd do it. You really got to think it over  and trust your gut -- in this case even more than your doctor. LOL. And don't feel any pressure to make the decision immediately. You'll know when you know.

Keep in mind two other things: (1) Only 41% of the study group was undetectable at 4 weeks. So that means if you take the short treatment approach there will be a 59% chance that you will have to stop treatment at the 4 week mark; and (2) Viral load can change dramatically. I went from 189,000 to 1.5 million in four months time. So that might argue toward tx while your viral load is still low.

But all in all, you're in a very enviable position (in a relative sort of way)given your stats. The odds are very much in your favor that you're going to beat the virus completely, if not today, then down the road.

[jmjm530]

If you're going to do your week #4 PCR, make sure you have the actual test it on day #6 (the day before your 5th shot.) That way you will get the "trough" result which will be the most conservative estimate of your viral load. And, of course, get a test with a sensitivity of at least <50.

[snook_man]

Here is the original trial that was conducted. The relapse rate is high for geno 1's and 24 week of tx, even with EVR. My original VL was only 4000, and I presented a few of these articles to my Dr and she just laughed and told me "No WAY".. Told me that it was 48 or more!
Also, the european quasispecies of geno 1's is different than geno 1 in the US..

You can find this article over at HIV and Hepatitis .com.. Check news articles and go to EVR.. There you can see the breakdowns and a few charts. Again, the SVR rate was alot lower than this study, and relapse VERY high...


In Genotype 1 Patients with Low Viral Load Who Become HCV RNA Negative at Week 4, Treatment with Peginterferon Alfa-2b (PegIntron) for 24 Weeks Has Similar High Efficacy with Superior Safety Compared to 48-week Therapy

The results of prior studies suggest that patients with genotype 1 patients and low HCV viral load (G1LVL) have high sustained virologic response rates (SVR) similar to genotype 2/3 patients. Recent data also have demonstrated that genotype 2/3 patients respond similarly with 24 weeks of therapy as historical 48-week treated controls.  

No similar data exist for G1LVL patients.  The objective of the current study was to compare the efficacy of 24 weeks of peginterferon alfa-2b/ribavirin (PegIntron/ribavirin/ P/R) with a historical control treated for 48 weeks with PegIntron plus a similar ribavirin dose (>10.6 mg/kg) (Manns, Lancet 2002).  

Treatment-na

[scruffy]

No debate.;)

[jmjm530]

I can't agree more about the potential toxicity of these drugs.

But regarding your tx length -- Are you a stage 3 or 4 as I thought Friole suggested in an earlier post? If so, I'd be wary of only treating 12 weeks.

The problem is that a lot of studies show the relationship between RVR, EVR and SVR. But they're not breaking down the data into the stage of liver damage.

So, on one one hand you get these great SVR numbers, and on the other you hear anecdotal evidence that 3's and 4's are big relapsers.

That's pretty much the dilemma I'm in. Rapid response RVR (sort of) (53) at week # 4, (<5) at week #6. But I'm a stage 3. So do I follow the RVR stats and treat less, or the stage 3 evidence and treat longer. I'm still holding off my decision. Hopefully, some newer studies will shed light or someone will break down the numbers a little better on the existing studies.

[rifleman]

No, I never said I was a stage 3 or 4.  More like stage 1.
DJL

[jmjm530]

The two studies sound similar but some of the numbers are different. The one I quote says 92% SVR versus 89% in yours.

That aside, I don't quite understand when you say, "the relapse rate is high for geno 1's and 24 week of tx, even with EVR." ?

We're talking about those who had a RVR at week #4. And I quote from the study as you presented which demonstrates an SVR of 89% in the special sub gbroup.:

"A subset of patients treated for 24 weeks, those who became HCV RNA negative at treatment week 4, had a similarly high SVR (89%) compared to the historical control (85%)."

As far as the Euro geno 1's, vs the American geno 1, I doubt if it would a significant enough differece. Let's say, the American geno 1's had a response rate of only 80% (same as geno 2's). I think that would still be pretty amazing.

It's not an easy call and that's why mostdoctors stick to the tried and true formulas handed out by the drug companies. But now, it looks like even those pat formulas will suggest 24 weeks for a special sub-group of  geno 1's. At least in Europe.

[jmjm530]

If you're a 2b, stage 1, you're in the driver's seat! If I were in your shoes, treating 12 weeks would be very tempting -- on the other hand, if you only did another 12 weeks you would be just about guaranteed your 80%+ chance of success.

[Califia]

I'm not going to wade into these studies, but I do want to reassure you that tx does not necessarily get (subjectively) worse the longer you treat.  In fact, had it not been for my battle with the vicious plant last week,  I would have to characterize the post-48 week period of treatment as relatively benign.   My chem profile has never looked better, suggesting that it's possible to adjust to a chronic level of toxicity.   Once you've gone 48 weeks, another 3 or 6 months are moot...or such has been one woman's experience.

[cuteus]

two women experience
stay well on the countdown!

[jmjm530]

Does anyone else here get the impression that overall the women here have an easier time on treatment then the men? LOL.

As far as the "vicious plant" syndrome, it's the one side effect that gives me nightmares. ;)

[artgal]

Here is why I will not allow myself to be tempted by this report and others similar to it -- and being a geno 2b grade 1 stage 0 46 yo female who cleared at 4 weeks, one might think I would jump on reports like this. And believe me, I would give anything to stop using these toxic, life altering drugs -- I've had the constant nausea, debilitating fatigue, anemia, mouth sores that only let up for a few days at a time, loss of appetite, general malaise and now (I spoke too soon last week when I so happily reported no hair loss) hair falling out regularly.
BUT (and I am in awe daily and have great respect for those who have treated and retreated) I never want to see another shot of interferon or ribavirin pill once I finish these 24 weeks. Maybe I would be one of the lucky ones to achieve SVR with only 12 weeks on tx -- I more than fit all the "requirements".
HOWEVER, these studies (for 2b's there have been only a mere 3 or 4 and for 1's this is the first I've seen discussing a shorter treatment duration) have been done with small groups of people, all of whom are European (which may make a difference according to some doctors), all with peg intron (not pegasys).
IF one follows the shorter tx and relapses (as many others before me have pointed out) the retreatment will be longer than the standard tx, the patient will no longer be treatment naive, and the genotype may have mutated and become a more difficult geno to treat.
Let's definitely continue to hope for better drugs or shorter tx possibilities but only act when more research and definitive studies have been completed.

[jmjm530]

Sorry about all the sides and maybe I'll take back what I previously said about women/men and side effects. LOL.

In your case I pretty much agree with your decision, picking 24 over 12 weeks. But what if the choice was 24 weeks versus 72 or even 96 weeks? Different equataion.

This stuff is really toxic and effects everyone differently. If I make it past 48 weeks I hope the sides will ease up, but it's really nothing I can count on.

As far as studies go, this one seems significant enough for the Europeans to change their protocol. And frankly, all the good/smart stuff in hep c research has always had Europe in the lead.

[Tallblonde]

Oh, I didn't mean to send any mixed messages with my comment about Roche.  I was just broadly speculating about their motives. Would it be right and fair for a company to avoid research that might lead to a discovery that a large group of people could benefit from half the standard treatment length?  Probably not, but I understand the necessity to make decisions based on economic reasons.  Companies, including drug companies, are primarly in business to make money.  I wouldn't expect them to invest a lot of time and energy into figuring out ways they could make less money.

I wasn't even implying that they were being greedy with my comment about "drumming up business."  If I was a shareholder in their stock, I probably would applaud their efforts to reach more potential users of their products. More than anything, I was trying to convey that we have to be aware of these possible motives when making individual treatment decisions.  

Susan

[Califia]

Rev:  Your willingness to reexamine a lot of assumptions about tx and this disease has been nothing but admirable.   I'm always plugging for you, guy.   And I know there's a lot of people hanging out in your corner right along with me.

jm:  Naw, it hasn't always been this easy.   Tx kicked me arse from day one and I've been through the gamut, too.   But the sides do eventually quiet down a bit.   The real bottom line is that once I resigned myself to not being a very productive citizen while on tx, it was easier to handle.   Sorta kinda.  This is to say that you may not write the Great American Novel this year, but you could well clear your hep.   How's THAT for encouragement?

Cuteus:  Guess we're going to have to put on our Tough Broad t-shirts!

[Califia]

Graceful clarification.   It IS maddening how much needs to be considered when we review medical research or any other scientific research, for that matter.  The first question, unfortunately, should always be who funded it, and why.   If we don't know the internal politics of the big players (and I, for one, can't pretend to), it's nearly impossible to follow the game.   Especially frustrating when your own body is on the line.  Whatever our own political persuasions, it's not a bad idea to pack the shareholders meetings of these companies.   All it takes is a minimal stock purchase to buy us admission.

[jmjm530]

No debate. :)

[Califia]

I agree w/ Rifleman:  do not, I repeat, do not accept the poisoned apple, however tempting it might be.  There's absolutely no need to suffer unnecessarily, although it sounds like Bro Rifleman has just spent the last few weeks at Betty Ford.   You've gone through enough of late, Susan, and don't need another demanding situation to test your mettle.

Quick question:  you seem to express disapproval of  Roche's "economic incentive" in launching the ad campaign.  Huh?  I thought you supported a vigorous, unregulated market and resented any criticism of  global capitalism.   Perhaps this is not the place to raise this issue, but I do sense a contradiction in your thinking and my curiosity is getting the best of me.   Hope all is going well....

[Tonyz]

Sorry I have been warned about using HTML code on this forum...


    But I cant stop you from learning on your own..


          Blessins..............TonyZ

[Forseegood]

Yes, I looked at this study with a hopeful heart when it came out. I am definitely going to do a pcr early, even if I have to pay for it, it's about 300 bucks around here. I have a 202,000 vl. and low damage. I know if I do clear early it will be hard for me to decide. I wonder if most insurance cos will do an eary one? I have spoken to some who had to stop treatment early, after 4 or 5 months, and they cleared anyway. I wonder if anyone is keeping up w/ their stats? That info would add in to all of this I would think?