Hep C Discussion Forum

pl1952 · Senior Member

RE: Advice on Continuing Treatment on COSMOS

BobK · Member

OldenSlow,

That is very interesting that 2 out of the 3 were clinically obese. I was wondering about that as well. I am not obese, but before my medications came, I asked the doctor if there was anything that I could possibly do to help the medications. He recommended trying to drop a little weight. My stomach area has a little extra baggage if you know what I mean, but nothing major at all.

My sister on the other hand is slightly obese and although she does not have Hep C, she is always have issues with her liver/gallbladder and doctors told her she has a fatty liver. So I could see where weight and fat might play a role.

I was considering going vegan for the rest of my treatment. Seems if I eat more on the vegan or paleo(sp) diet with less meat, I feel a lot better.

OldenSlow · Senior Member

Bob - You're absolutely correct. We don't have enough information to draw solid conclusions about much of this. We can attempt to make the most informed decisions possible, but that's about it. And as Malcolm suggests, I'm sure there's plenty we're not even being told. Just an opinion, but I don't think diet or supplements play an overriding role with this disease. They certainly can with respect to lifestyle and overall health, and clearly being seriously overweight would complicate things. BTW, they did measure BMI in COSMOS. Two of the three relapsers were clinically obese.

Isiscat - The info came from Clinical Care Options I don't link it directly as it's a subscription site. It's free but many don't want to jump through the hoops. Good resource though, for those interested. The page I drew from is here should you wish to sign up:

COSMOS Cohort 2

wayne

mallani · Guru

It's clear that RAVs R155K and D168E are bad news for the Geno 1a's using antiproteases. I think I saw that MK-5172 could cope with them.

I don't believe the Sovaldi RAV details. As Sovaldi is the mainline drug, relapse only occurs if the main drug and the backup fail. I suspect Sovaldi RAV's are so transient that they have reverted to wild-type or an unrecognised polymorphism before testing takes place. S282T is not found, but is virtually identical to S282S which can't be measured. There's still a lot we haven't been told.

Isiscat2011 · Guru

OldenSlow wrote:
Of the two forum members I'm aware of who relapsed after treatment with S/O: one was treated for 16 weeks after being und @ 2 weeks; the other treated for 12 weeks and took longer than 4 wks to become und.

I believe both who relapsed also had significant liver damage (bridging fibrosis/F3-F4). That commonality keeps popping up, doesn't it?

Isiscat2011 · Guru

Very interesting, OldenSlow. So, the commonalities are that all were 1as, all had significant fibrosis (F3-F4), all had Olysio related mutations at relapse (but not the same type), none had Sovaldi mutations, all were white males, and all were treated for 12 weeks.

I'm not sure that we can draw any real conclusions particularly since there were only 3 people. The conclusion that 1as don't do as well is supported here (and is supported by the clinical trial results). I was thinking that was connected to the Q80K, because only 1as tend to carry that polymorphism, but perhaps not. This also supports the conclusion that people with more serious liver damage don't fare as well which isn't surprising.

I wonder if treating all for 24 weeks would have made the difference.

You find some good stuff, Wayne. Where did you find this?

Fireman Rob · Senior Member

Great Info! One consistent but preliminary factor that's on my mind is according to all the limited stats we have on this combo, adding Riba doesn't seem to make much difference at all. It will be very interesting to see how SVR rates continue to develop over time.

Good Stuff Oldenslow!

BobK · Member

Good information OldenSlow. Not enough data to come to any conclusions, but very interesting no less.

Too bad they don't keep records on things like weight...diet or other factors that may influence this virus after treatment. Maybe certain foods or bad habits...anything that showed a pattern.

I know grasping at straws, but you never know. I was wanting to see if diet played a role at all. Like someone being vegan as opposed to someone eating meats would increase chances of staying UND.

Anyway interesting topic.

OldenSlow · Senior Member

Hi Bob,

Sounds like you're thinking along the same lines I was when I didn't come back und at 4 weeks. Like you, my doctor had no objection to extra treatment time, provided we could get insurance approval and we ultimately did. So, I did the 16 weeks (w/riba) and remained und at 4 weeks post-tx. Given my cirrhosis, I figured the extra time certainly couldn't hurt. It was a decision based on the information I had at hand, as insufficient as that may have been.

Of the two forum members I'm aware of who relapsed after treatment with S/O: one was treated for 16 weeks after being und @ 2 weeks; the other treated for 12 weeks and took longer than 4 wks to become und. In the COSMOS trial there was a sizeable percentage who took longer than 4 wks to become und and it seemed to have no effect on end result.

For what it's worth, the box below shows the details of the 3 who relapsed in Cohort 2 of COSMOS. All were GT 1a. You'll notice two of them were und @ wk 4.

*Characteristic*	*Relapser 1*	*Relapser 2*	*Relapser 3*
Age, yrs	58	36	47
Sex	Male	Male	Male
Race	White	White	White
BMI	24	39	33
HCV genotype 1a with Q80K	Yes	No	No
IL28B genotype	CT	TT	CC
Baseline HCV RNA, log10IU/mL	6.2	5.2	6.4
METAVIR score	F4	F3	F4
Treatment history	Previous null responder	Treatment naive	Treatment naive
Assigned to receive ribavirin	Yes	Yes	No
Treatment duration, wks	12	12	12
HCV RNA at Wk 4	Undetectable	Undetectable	Detectable, but HCV RNA < 25 IU/mL
Time of relapse	4 wks after EOT	8 wks after EOT	8 wks after EOT
Mutations at relapse
Simeprevir-associated mutation	D168E	R155K	D168E
Sofosbuvir-associated mutation	None	None	None

Isiscat2011 · Guru

Groupergetter wrote:
I had spoken to my doctor about extending the treatment on S/O. She as we already know, stated insurance companies rarely approve more than 12 weeks. We need to remember this is still an off label regimen. I suspect for those relapsing after 12 weeks tx, longer periods may be approved. I have a call into Gilead with other questions, and will include this when they respond. For those on treatment and those getting ready to start good luck. Maybe we should all try and consider this a roller coaster ride?

I suspect your suspicion is correct, Groupgetter. smile

Good idea about considering this a roller coaster ride. I also think of it as a marathon not a sprint (although I sure would have preferred a sprint).

Groupergetter · Guru

I had spoken to my doctor about extending the treatment on S/O. She as we already know, stated insurance companies rarely approve more than 12 weeks. We need to remember this is still an off label regimen. I suspect for those relapsing after 12 weeks tx, longer periods may be approved. I have a call into Gilead with other questions, and will include this when they respond. For those on treatment and those getting ready to start good luck. Maybe we should all try and consider this a roller coaster ride?

mallani · Guru

Hi Huey,

I'm not sure why you think Insulin Resistance (IR) is a feature of Genotype 3. It is more common in chronic HepC, across all Genotypes, and Geno 1's have the highest incidence.

The relationship between IR, type 2 diabetes (DM-2), obesity and liver fibrosis has been the subject of extensive research. It is complex and there are no definitive answers. The previous impression was that HCV led to IR, which led to DM-2, which led to increased liver fibrosis and a poor response to Rx. This has not been proved by recent studies.

What has been shown is that obesity (BMI >30) is associated with fatty liver and probably IR/DM-2.

Huey · Guru

Tig56 wrote:
Huey,
People don't have the luxury of selecting how many weeks they want to be on these protocols. You qualify according to your laboratory work ups, history of treatment, successes, failures and doctor recommendations. While there are some instances, like Oldenslow's case, when he and his doctor discussed the possibility of an extension, the application was made through his insurance carrier for an additional 4 weeks of treatment. But each request must be met with adequate supporting documentation and labwork. Ultimately the decision is made by your insurance carrier, based on labs, history and supported appeals by a carefully orchestrated process delivered by your primary and secondary health care teams. Good luck on completing your course of tx. I'm glad your toe rot has improved so well!
Tig

Thanks man... I realise these hoops have to be jumped through, you may not have full controll but you can "Actively seek" This, and if you don't ask the insurance, you will never know, They may think it is cheeper to buy more drugs than to risk a setback.

-- Edited by Huey on Thursday 3rd of July 2014 02:04:41 AM

Huey · Guru

BobK wrote:
Thanks for responses.
Like I mentioned I did not clear at week 4, but my Doctor who is at UM Liver Disease clinic, said EVERYONE is eventually clearing and six weeks seems to be the magic number.
I think I am somewhere between stage 2 - 3 fibrosis and overall feel pretty good. I could tell at 4 week I still had it. At six weeks I really can't tell if it is there or not. My doctor told me of a story that a lady thought her ammonia level was through the roof and she just knew it was high. The doctor took a test and it was perfect. He said he has people all the time telling them they are sure this or that is off, but almost 100% they are wrong. So in other words he was telling me not to think to much into the way of how I am feeling, just know it is working and keep a positive attitude.
And yes Tig, I was thinking it would increase my odds. The two people I have been in contact with did not clear at 4 weeks either, but did stop treatment at week 12. I am so looking forward to becoming UND here very soon.
I really wish we understood more why some people relapse and some do not. Did the virus hide or was dormant cause it knew it was under attack? Would diet and life style play a role after the 12 weeks is up? So many factors, that is why I was hoping by now people on the forum may see a pattern or notice something about these newer treatments that may not even be documented yet.

I have been looking at one.... In Geno 3 you get Insulin resistance, I have talked about this before and I am looking to see if others follow my pattern, When my VL went down, my sugar went up. even after my vl was UND my glucose was going up, then peeked , then went down rather quickly back to normal. This is that insulin resistance that makes the sugar go up,the virus does this, SO if my glucose should spike after EOT I will take that as the virus is back, I think this will show up even sooner than the VL test and may be a way to preempt a relapse.

Isiscat2011 · Guru

Hi Bob:

As you already know, nobody can predict outcomes with any degree of certainty. We can only reach speculative conclusions based on limited clinical trial data and anecdotal information. Based on what I have read both here and of the clinical trial results I would not be too concerned about extending tx if I did not have substantial liver damage and had tested negative for the Q80K polymorphism. Quite honestly I doubt insurance would approve another 4 weeks without any strong reasons to do so.

I would reconsider the question if not UND at 6 weeks but, again, that may not be sufficient reason for the insurance company to extend.

Isiscat2011 · Guru

Thanks, RH. Your take is probably correct. Either that or they just aren't saying what they do know. smile

In any event the 24 weeks should do it. That was what surprised me--because I thought it was a 24 week tx relapse.

BobK · Member

Well here is a little info...

What is your genotype? 1a

What is your liver fibrosis score? I was told stage 2 - 3 fibrosis

At what week did you become UND? Still not UND @ week 4. Just took another blood test at week 6 and doctor felt I would be UND by now.

What is your previous treatment history? I was in a trial study back in 2012, but did not clear and ended trail 2 weeks in.

Do you have the Q80K polymorphism? No I did not

Any substantial side effects? Zero side effects so far.

Are you presently on a 12 week clinical trial with Sovaldi/Olysio? No this was prescribed off label by my doctor cause I requested it. He has a lot of patients on this treatment.

July 1, 2014 was my sixth week. I have had Hep C for well over 35 Years.

I was really hoping to just kind of stay on topic and see if someone chimed in about my initial question. Maybe now everyone can see exactly where I'm at in my history and protocol.

I completely understand that it is still early in the game for these new drugs, just looking for the best case scenario during and after treatment.

I kind of feel even the doctors do not know much about it.

HR · Senior Member

Isiscat2011 wrote:
Hi RH:
Sorry to get off topic for a minute here but I just noticed you relapsed on the 24 week S/L combo. I'm very sorry to hear this.
Do you have cirrhosis? Any explanations on why this happened from the clinical trial team? Will you be starting another DAA soon?

I relapsed on the 12 week trial of Sof/ldv. I am currently taking the same meds and am on week 22 of the 24 week Ion-3 relapse trial. I was 3-4 on the ischank (sp) scale which goes 0-6. So I'm right in the middle. At first they were saying I probably became resistant to Ledipasvir and now they are saying I just didn't take it long enough and that 12 weeks wasn't long enough to become resistant. My take- they don't have any idea.

Isiscat2011 · Guru

Hi RH:

Sorry to get off topic for a minute here but I just noticed you relapsed on the 24 week S/L combo. I'm very sorry to hear this.

Do you have cirrhosis? Any explanations on why this happened from the clinical trial team? Will you be starting another DAA soon?

suziq · Senior Member

Hi Bob,

I have no idea. I did a Merck trial and I got the arm of 18 weeks with ribavirin. When I was at my trial center for my last labs(EOT+24) on Monday, the coordinator did say that I got the very maximum treatment in the trial and she was sure I would still be UND. Given my age and cirrhosis, I am glad I got that arm of the trial. The meds are so new and the data based on so few people that it is hard to say what is best. The previous data was based on 121 people and 32 were in my 18 week arm.

The decision is between you and your doctor. Good luck however you go !!!

Tig · Admin

Huey,

People don't have the luxury of selecting how many weeks they want to be on these protocols. You qualify according to your laboratory work ups, history of treatment, successes, failures and doctor recommendations. While there are some instances, like Oldenslow's case, when he and his doctor discussed the possibility of an extension, the application was made through his insurance carrier for an additional 4 weeks of treatment. But each request must be met with adequate supporting documentation and labwork. Ultimately the decision is made by your insurance carrier, based on labs, history and supported appeals by a carefully orchestrated process delivered by your primary and secondary health care teams. Good luck on completing your course of tx. I'm glad your toe rot has improved so well!

Tig

HR · Senior Member

Hi Bob

Is this Cosmos a clinical trial ? I'm not sure what that is.

Thanks

Isiscat2011 · Guru

Hi Bob:

Need more information to offer an opinion: What is your genotype? What is your liver fibrosis score? At what week did you become UND? What is your previous treatment history? Do you have the Q80K polymorphism? Any substantial side effects?

Also, are you presently on a 12 week clinical trial with Sovaldi/Olysio, and if yes, when did you start?

BobK · Member

Thanks for responses.

Like I mentioned I did not clear at week 4, but my Doctor who is at UM Liver Disease clinic, said EVERYONE is eventually clearing and six weeks seems to be the magic number.

I think I am somewhere between stage 2 - 3 fibrosis and overall feel pretty good. I could tell at 4 week I still had it. At six weeks I really can't tell if it is there or not. My doctor told me of a story that a lady thought her ammonia level was through the roof and she just knew it was high. The doctor took a test and it was perfect. He said he has people all the time telling them they are sure this or that is off, but almost 100% they are wrong. So in other words he was telling me not to think to much into the way of how I am feeling, just know it is working and keep a positive attitude.

And yes Tig, I was thinking it would increase my odds. The two people I have been in contact with did not clear at 4 weeks either, but did stop treatment at week 12. I am so looking forward to becoming UND here very soon.

I really wish we understood more why some people relapse and some do not. Did the virus hide or was dormant cause it knew it was under attack? Would diet and life style play a role after the 12 weeks is up? So many factors, that is why I was hoping by now people on the forum may see a pattern or notice something about these newer treatments that may not even be documented yet.

Huey · Guru

Hi,, I can't relay answer your question but I think i can come close. I am on a 24 week tx/ and I know how i feel at 12 weeks and beyond. First you have to understand I happen to respond to the sovaldi Vary Vary well. I had a rapid VR and showed UND in 3.8 weeks, and i have remained UND and continue too. Right now I feel as though it is gone. In fact my skin is even white. The Rot on my big toe nails are healing. In my case I be leave that 18 weeks did it. But I am still going to get this for the entire 24. error on the side of caution and take it longer if you have to, and Increase of 18 I THINK would do it, but I would go for 24.

We are all in this together , Keep your stick on the ice. Red green show/

Tig · Admin

Hi Bob,

We have a member "Oldenslow, Wayne" that did just that, extended treatment out to 16 weeks, because he was able to and remains UND to date. There is such a wide array of factors that might make a bit of a difference in the outcome, but they are "wide and varied"! The studies and reports continue to show limited differences in the SVR outcomes and I believe it's going to come down to a simple decision of whether you feel there is a significant increase in odds. I don't believe the research holds much in the way of improved chances overall. Now if you're cirrhotic, that would certainly make your odds better (imo), but I don't see you mention that as a problem on your profile. Do you have any outstanding factors that we're not aware of that would provide support for extending it beyond 12 weeks? If you've met all the treatment criteria for a 12 week protocol, and been successful to date, I see no documentation that would suggest an additional 4 weeks of treatment increasing your odds of SVR beyond what you're already witnessing. I do want to point out that your comment on "most" people clearing the virus between week 2 and 4 isn't necessarily true. From the discussions here and anecdotal evidence I've read more and more of lately, we're seeing more reports of confirmed clearance between weeks 6 and 8. The VA has finally released a determination (futility testing) that calls for an initial VL at week 4 and if memory serves me right, testing again at week 8, which if still detectable, treatment is recommended to stop. As far as I know that's only a VA requirement here in the states. We're seeing many doctors waiting until EOT to do a first VL and then a final at EOT +12 to determine SVR. I would like to see a definitive futility rule established with each new protocol, but with the frequency of protocol changes we're witnessing now, I'm not sure those individuals in R&D know exactly what to plan for next. It's a very turbulent time in the laboratory right now...

Tig

BobK · Member

Hi All,

So at week 4 I was at the lowest detection VL rate before being undetectable. So the doctor said he was beyond positive I would be UND at week 6 and said he would eat his shoes and shave my initials in his hair if I wasn't. He said the real test is 12 weeks post treatment. So I told him that wouldn't it be a good idea to continue the treatment for another 4 weeks just in case. Cause most people were clearing at 2 - 4 weeks and had all the other weeks to keep the virus from coming back. But at 6 or even 8 weeks, the length of time would be less for the medication to stay in your system being UND.

The doctor said he would do whatever I wanted. He said I might have to fight the insurance company, but he would be willing to write a script for four more weeks of treatment after the 12 week period. He said there was not enough data to know if that would really make a difference or not.

So my question is...is there anyone out there that might know if extending treatment helps in the end results?

Thanks for reading.

Bob

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