Pegasys v PegIntron

[CockSparrow]

Not sure if this has been posted before but Roche seem to be happy that the first head to head study (IDEAL study) comparing both Peg molecules came out a draw.

http://www.medicalnewstoday.com/articles/94184.php

The announcement made by Schering-Plough on the early results of the IDEAL study affirms the importance of Pegasys (peginterferon alfa 2a) and Copegus (ribavirin) for the successful treatment of hepatitis C. The study demonstrates that Pegasys and Copegus treatment delivered a similar sustained virological response (SVR) - the key measure of treatment success in hepatitis C - to Schering's peginterferon alfa 2b. This is in spite of projected inequalities of ribavirin exposure, which may have potentially biased the results in favour of the Schering Plough regimens. The study provides further support for the position of Pegasys as the leading treatment for hepatitis C patients.

In the trial Pegasys and Copegus treatment delivered an SVR of 41%, compared to peginterferon alfa 2b and ribavirin which showed 38-40% SVR in the two peginterferon alfa 2b and ribavirin arms of the study.[i] The Pegasys treatment arm of the study confirms the consistent, proven efficacy seen in earlier trials in genotype 1 patients (the most difficult to cure strain of the disease).

CS

[Myown]

Well I don't know.... but, i too had a sinus problem on tox that did not respond to anti biotics. It caused a problem with infection in my lower eye lid that I carried throughout tox and cleared only after I was finished. I relapsed so who knows, you may be on to something.
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Well, as I always say, ,,,can't just get back on the trolley track. A person has to try their best to see what the probelm is with their immune system. Of course we might never know, but just think if I didn't take it upon myself to go to a para doc and a Neurologist....I would never have found out that I had para's cause Lab Corp said I didn't,,,and the Rheumy didn't think much of the little tingles I was getting, but I did and took it upon myself to go to a Neurologist and bingo - found out I have Neuropathy, so forget about even remotely thinking that a hepatologist can handle all the possible things that can happen with this disease or that he would have all the right answers - no matter how good he is, they don't know it all and they DO NOT have enough of an understanding of the immune system IMO and the kicker is,,,,the immune system is the heart of this entire disease!  I was thinking the other day and said to myself,,,Okay they do let the white cells go very low,,,,BUT how about giving us a shot of that Neupogen a few weeks before EOT so that we have extra white blood cells once the tx ends - so that it can help in the fight against mutants and prevent relapse.......maybe I don't know enough or maybe I am off base,,,but I will give my theory to my doctor. I can understand letting the white cells go low while ON tx,,,cause the artificial interferon  and riba is like our body guard or soldiers,,,but once our troops go home,,,,how bout a shot of Neupogen for our white cells to get more help......As I said, I don't know enough about this stuff yet,,,,but I'm trying. Helps me to feel like I am doing something to help myself and in a few instances I have.

[gauf]

Well I don't know.... but, i too had a sinus problem on tox that did not respond to anti biotics. It caused a problem with infection in my lower eye lid that I carried throughout tox and cleared only after I was finished. I relapsed so who knows, you may be on to something.

[Myown]

CS "One other thing how much do we contribute. Maybe we are partially to blame in one way or another. For example the drugs are water soluable.
Does the amount of liquid we drink on Tx speed up the drugs clearance by the kidneys?
Dont know for sure but maybe. Does diet contribute to success?
Are we dificient in certain vitamins or minerals etc "
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Yup, I agree ,the water I def have to watch cause I drink too much water even when not on treatment. I like water, tea and all that, so I am always sipping on something and maybe thats no good. As far as the vitamins and minerals, I have always taken them and have had tests to see what my levels are and with some, my level was a little low and that I believe is because of the body drawing from all these to ramp up the immune system,,,BUT,,here's the thing,,,,I am afraid now that some of the supplements can or may block the meds from working (as HR discusses as far as not knowing the effects of certain supple. on tx) sooooo, I have cut back to pratically nothing - just some vit C and some NAC and thats it. I hate doing this cause we certainly don't get enough from the foods we eat, no matter how healthy you eat, especially with me living in the NYC area, so much pollution.

But I do have another theory as to why I relapsed........we all know that immunosuppressants can cause someone to go from svr to relapse,,,well, here's the deal,,,when I had the parasites (which I believed was from being immunosuppressed more than anything else - caused overgrowth) well anyway,,,,,I got rid of them, but I think I have an intestinal fungas - sounds gross, but bear with me cause I think many people may have this and it may be the reason or part of the reason some do not respond OR respond, then relapse,,,,,,Okay, when my bx (post tx) showed up that I have microgranulomas and I read that these micros are mainly seen in post transplant people,,,,,I said to myself,,,,,what do I have in common with a post transplant person?
The answer that came to me was that I was obviously 'immunosuppresed" because of the parasites, which intestinal candidas (not the vaginal kind - didn't have that) and intestional fungas can possibly go hand a hand.

If you read anything about immunosuppressive drugs, you will find that they are made from fungas. Many drugs are. So maybe these granulomas seen on some PT's are from fungas or parasites, from taking the immunosuppresive drugs - just guessing, its my opinion, and I wish someone would have looked inside these little tumors to see what was in them,,,,but I am picking up my slides and I will find out somehow.

I have often wondered why some transplant patients have difficulty clearing the virus and maybe (?)cause IMO they are on these immunosuppressive drugs - which of course they need to be unless the doctor weens them off sucessfully.

But anyhow getting back to my problem, I believe the health of the intestines is vital in order to svr. I read a study that said HCV can replicate in the intestines, so if the intestines are a problem or condusive for replication such as imbalance of flora due to candidas or fungas or parasites etc....that would be a problem.

If the person has a fungas or candidas in their intestines, IMO I believe this can be a very big concern and may cause relapse. Prior to dx when I was searching to find what was wrong I had a real bad sinus type infection and the doctor put me on very strong antibiotics but it didn't help. I think it didn't help cause he didn't first dx if the infection was viral,bacterial or fungal.....IF a sinus infection is not txed with the correct meds, it will make the problem worse......Okay, so this is why I am still not txing, I need to know if I have a systemic or intestional fungal/or candidas infection,,,,,,IMO IF I DO,,,,it will be like being on immunosuppressants like prednisone or whatever once I finish tx and am UND, it will only take a matter of time for the vl to slowly come back. There are many people on forum who have had overuse of antibiotics prior to starting tx and IF the correct balance of flora is not in the intestines,,,,as your white cells go low on tx,,,,overgrowth of candidas/fungas will inevidenly happen IMO. I made an appointment with an Immunologist and spoke to her about it and it made sense to her after I said it, but I didn't get any suggestions or help coming from her. She seems to deal more with allergies. I was going to call a Microbiologist and make an appointment with him, but I saw there seems to be a scandle that he is caught up in with monies or something,,,,,so I will go talk to the para doc again. Of course taking tons of Probiotics and the Alina and thats the best I can do right now,,,but I know I am right as far as my case - can't speak for others,,,,but I feel a persons intestional health is very important IF one expects to attain svr. Do ya see what I am saying,,,IF there is an overgrowth of intestional candidas of fungas,,,,it will act as an immunosuppresant drug at the end of tx. So my plan is A) first find out IF I have this problem, B) treat it with whatever meds they suggest - usually a "azole" from what I have read. C) suggest to my doctor that at EOT to go back on the "azole" in case the fungal/candidas tries to come back while my immune system is in a weakened state....this way the azole will be attacking any intestional problem that may be arising and it will take the strain off my T cells and allow them to fight the left over mutants.

I know it may sound crazy to many, but this has come to me very clearly AND I really have not been wrong with any of my dx thus far - though I have had to fight tooth and nail to get all my doctors to finally see the light.

BTW Bobby posted he had a systemic fungal infection that his doctor spotted - in his throat. Since this was something that I have been researching, I PM'd him and sure enough his doc did have to tx it with an antifungal. So that was sort of a confirmation to me that I might be on track. Well actually, I never doubted that I am on track. BTW cancer patients - not all, some, can get systemic fungal infections after being on chemo.So again, think of it, immunosuppressant drugs are made from fungus - so wouldn't it make sense that if your body was producing a fungas, it would be the same as maybe taking prednisone at the end of tx?

So anyway getting back to BoBBy,, I knew at that point, I may not be off course with my theory - that many of us, due to the strain on the immune system can get fungal type infections - some not visable, some with manifestations of some sort.

Well anyway. All of this will be disgussed with my hepc doc, after I see my other doc.

seeya later.
good talking to ya,
MO

[CockSparrow]

MO
Your 16mil VL = 7.2 Logs
Your 5 Mil VL = 6.7 Logs

Wotcha worrying about its its 1/2 a log different and within the PCR test variance.
Its the same number it hasnt gone up nor has it gone done.
Which is what you would expect. Alinia doesnt work as mono therapy.
If you pre dose the riba it wont change your VL either.

MO -  don't understand why the SVR rate goes down for re-treaters

I do. When you retreat something has to change. Retreating with exactly the same regime will more than likely produce the same result. It does have a success rate though.
So what changed for those who SVRed??

The obvious change is to extend. This may not be enough of a change for some.
Another change is Induction dosing. etc.
You are changing heaps extending beyond 48 weeks would appear to be somewhat overkill.

One other thing how much do we contribute. Maybe we are partially to blame in one way or another. For example the drugs are water soluable.
Does the amount of liquid we drink on Tx speed up the drugs clearance by the kidneys?
Dont know for sure but maybe. Does diet contribute to success?
Are we dificient in certain vitamins or minerals etc

Just a thought
CS

[Myown]

desert quote"Remember interferon has never been dosed by what's effective - it's dosed by what the human body can tolerate."

Yes, you're right thanks. That is something that I have to consider.

CS,quote"Howerver the only study I can find re-treating G2-3 relapsers (it was a follow on study from NV15942 which was the Pegasys registration trial) treated for 48 weeks. It had an SVR rate of 66% for G2s. sounds good till you realise that this was 4 out of 6 (it was 5 out of 8 for G3s). The G1 SVR rate was 55% which isn’t bad considering."

I don't understand why the SVR rate goes down for re-treaters. My hep doc told me that it would be easier to SVR cause my T cells have been trained. I think I should treat longer than 48 weeks. Maybe should tx 60 weeks and then taper...well I'll see how it goes. My VL is not coming down with the ALin.. I thought it was cause the first test took longer to come back than the regular labs,,,but when it came back it was 5 million - 3 weeks later it was 16 million. Uut oh.lol  I guess soon I will be talking and virons will start falling out of my mouth and ears and caught in between my teeth when I am eating.  fun, fun fun. Hopefully once I add the SOC, the Alin..will do its job:) If not, nothing I can do, its too late and I don't want to stop it now since I already started.

Seeya,
MO

[CockSparrow]

While we may disagree on what attaching Roche's peg molecule to Intron-A would achieve. I like the way you think.
What I would like to see is Roche's Peg attached to Infergen.
Now that could be quite a drug. But like you say wont happen.
CS

[CockSparrow]

MyOwn
Roche re-treated PegIntron relapsers with 5 day dosing. So you would think they have at least an inkling that this dosing schedule is better for at least some of us. They got a 20-25% SVR rate btw.

As for what to do when you switch back I like the idea of tapering. After taking 360 drop to 270 for a couple of weeks then drop to 180.

Whether you can do the shots every 5 days depends on how well your WBC and platelettes held up last time. DD every five days could be harsh on both you and the virus. What desrt says is true
“interferon has never been dosed by what's effective - it's dosed by what the human body can tolerate”. So I would take what I could tolerate.

Quote - would you add extra time on at the end, being you would end the tx earlier than 48 weeks?
This is something I am still wrestling with. The Drusano model says G2s-3s should do 36 weeks.
Howerver the only study I can find re-treating G2-3 relapsers (it was a follow on study from NV15942 which was the Pegasys registration trial) treated for 48 weeks. It had an SVR rate of 66% for G2s. sounds good till you realise that this was 4 out of 6 (it was 5 out of 8 for G3s). The G1 SVR rate was 55% which isn’t bad considering.

From a purely SVR goal I would extend but I am not sure for how long. Either way I like the idea of tapering at the end as well.

I think its good that you are not rushing into it.

All the Best
CS

[desrt]

CS:
I disagree that combining Roche's PEG with S-P's IFN would necessarily leave you with just another form of Pegasys, but the question is moot since it will probably never be done.

MO:
Every five day dosing with Pegasys has been tried before. If mkandrew.com were still accessible you could read his experiences with this. Remember interferon has never been dosed by what's effective - it's dosed by what the human body can tolerate.

[Myown]

Again, thank you so much for the info. Pegasys every 5 days sounds good to me. Okay, question,,,IF I was planning on doing double dosing just until I was UND and then just doing the rest of tx one shot every 7 days,,,,what would you do NOW IF you were doing the shot every 5 days (after the double dosing ended AND ya know what?? should I DD every 5 days instead of 7 until UND?- guess so, right??),,,would you add extra time on at the end, being you would end the tx earlier than 48 weeks? I know none of us really know for sure, but I just want your take on it. I hope I made sense to you. I just read it back and it sounds confusing, but its the best I can do at 6:28 am.

I am still making my rounds cause I still feel unsettled about a few things. After I get all the info and all that(and now also discuss what you mentioned above), I'll let ya know my plan cause things are still up in the air about a few things and rather than repeat myself or say one thing and then change it - I'll wait until I am ready to stick the needle in my stomach, cause at that point I will be totally decided and know which way I am going.
Thanks again,
MO

[CockSparrow]

While I agree that the Roche Peg molecule is superior to Scherings wouldnt attaching it to Intron-A make Intron-A Pegasys. What I mean by this is that both Interferons only have one minor difference in structure, they are essentially the same drug. The difference is only there to get around patent laws.
The peg molecule changes the pharmacokinetics of the drug and results in increased IFN exposure. But the price of this is that it doesnt hit as hard. Non Peg IFN can produce anywhere from a 0.5 log to 2 log drop after the first shot.
Both Pegs take up to a week to do the same thing.
I would like to see more done with optimizing the pharmacokinetics using all IFNs available as each behaves slightly differently.
CS

[desrt]

Thank you for the update on IDEAL, but to me the more interesting question remains, 'why' do the results keep coming out a draw? It's been known for over five years - before Pegasys was even released on the market - that the branched PEG molecule in the Roche product gives it a superior half-life, yet, when all else is made equal, PegIntron and Pegasys work equally well. The 2-3% variation in results can always be written off to riba dosing, patient compliance, who's doing the testing, etc, etc.
Interferon exposure should trump everything, this is why no one does Roferon or Intron A anymore. Until interferon alpha 2b can be bonded to the branched PEG molecule that's used to deliver interferon alpha 2a there can be no true "head to head"  comparison of the two interferons.

[CockSparrow]

Nah never been a Vitamin type. I am also a sceptical bugger and couldn’t just take HRs word for it.
Once I realised that it was mainly anti-oxidents, I thought I’d try it and just monitor my bloods and see what happens.

As you like some of my posts (thanks for the complement) and as you are going to see another Hepatogist here is something to think about and maybe ask about.
Probably applies more to me than you.
But it could be a reason for relapse as well as non response.

From the Pegasys Product Info sheet.

Pharmacokinetics
Maximal serum concentration (Cmax) and AUC increased in a nonlinear dose related manner following administration of 90 to 270ug of PEGASYS.
Maximal serum concentrations (Cmax) occur between 72 to 96 hours post-dose.

Week 48 mean trough concentrations (16ng/mL; range 4 to 28) at 168 hours post-dose are approximately 2 fold higher than week1 mean trough concentrations (9ng/mL; range 0 to 15)
Steady-state serum levels are reached within 5 to 8 weeks on once weekly dosing.
The peak to trough ratio at week 48 is approximately 2.
The mean systemic clearance in healthy subjects given PEGASYS was 94mL/h which is approximately 100 fold lower than that for interferon alfa-2a (ROFERON-A)

The mean terminal half-life after sc dosing in patients with Chronic Hepatitis C was 80 hours (range 50-140 hours) compared to 5 hours (range 3.7 to 8 hours) for ROFERON-A.

Now to me the last sentence says it all. The average half-life of Pegasys is 80 hours. Notice how this is in the middle of the maximum serum concentration time of 72-96 hours.
The bit that interests me is the range 50 to 140 hours Pegasys half life.
The Week1 mean trough concentrations (9ng/mL; range 0 to 15) is also interesting especially the zero bit.
Anyone want to bet that if your clearance of Pegasys is closer to 50 hours than 80 you have lower SVR odds. Bet the closer to 140 the more sides to.

Seems to me that Pegasys every 5 days could be a reasonable option for some of us.

Pity we are not tested for IFN clearance ay.
CS

[Myown]

Glad to hear that you are doing good and also good to hear that you are doing HR's supplement list.

I'm surprised you haven't been taking them all the long. You've never been into vitamins? Well, I'm glad you're taking them, it will do your liver good. What stage/grade are you? I was going to PM you the other day cause I wanted to thank you for jumping into my threads when I have questions. I like your answers. You know alot.

Okay, so the study was not on even ground and yet it back fired for Scherring - thats funny. I guess its good then that I will be doing Pegasys again. I'd like to get started, but I want to go to one more doctor and ask some questions.

I can't wait for the day when there is a vaccine that no one has to go thru what we all go thru with this crumby disease. All these doctor appointments can really get on your nerves.

Okay Mr. CS, time for me to hit the sack - gotta get up early tomorrow.
Good talking to ya,
MO

[Myown]

The FDA said the study was faulted and never should of been approved in the first place. The pegasys arm was with 1000 mg of Ribavirn and the Pegintron arms were with weight based Ribavirin.
    Drs on Clinicaloptions mentioned this also. They said that to compare them, both should of been weight based. What I get out of it is Roche is happy because they had the same results even though their Medicine wasn't given with weight based Ribavirin.

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Thanks Bobby, Yeah I just didn't understand it, the way it was written. Something didn't make sense. And its sad some of these folks in the studies aren't really given a fair chance to SVR, but I guess they know that before they go into the study.
Seeya later,
MO

[CockSparrow]

Hi MO
Yeh doing good, how you doing.
Just started HRs little supplement list. God there are a lot of pills to take. Some not that easy to get here. Doesnt help when they have different names either.
I intend to monitor my ALTs and see what happens. Back to the study.

The study was setup to compare 1.0ug/kg vs 1.5ug/kg PegIntron.
Scherring decided to be a smart @rse and add Pegasys to compare against.
Guess they were hoping that Pegasys would have lower SVR rates or at least fall in the middle of the 2 PegIntron arms.

The problem is that Roche and Scherring have different Riba dosing regimes and different recommendations for reducing the Riba.
Roche drop down to 600mg in one hit while scherring drop in 200mg increments.

What all means is that when reducing the Riba you are not really comparing apples with apples.
Thats why Roche seem to be happy about it all as it validates their Riba dosing recommendations.

A proper breakdown would be interesting
CS

[Bobby1952]

    The FDA said the study was faulted and never should of been approved in the first place. The pegasys arm was with 1000 mg of Ribavirn and the Pegintron arms were with weight based Ribavirin.
    Drs on Clinicaloptions mentioned this also. They said that to compare them, both should of been weight based. What I get out of it is Roche is happy because they had the same results even though their Medicine wasn't given with weight based Ribavirin.

Bobby

[Myown]

Hi CS! Hope all is well.

I have to read this again later. I am running out,,but it confused me while I was skimming thru it - with the riba reduction and all that. I don't understand why the loser is announcing this,,,,is there a merger of the Pharma's in the making or maybe I am not understanding something. I have to read this again later when I get time, but if anyone wants to break it down and explain why they did the study the way they did with the dose reduction when dose reduction is NOT something that we would normally do, that would be good. I don't get it, but I will read it again later and maybe it will sink in.

Seeya later!
MO

[gauf]

I have done both and I prefer Pegasys and Copegus as the sides were less for me.