Interferon question, alpha 2A/2B

[geterdone]

Does anyone know or can point me in the right direction as to what is the major difference between the two other than manufactures interferon’s and are there any major differences in the side effects of each.
Thanks
Jasper

[desrt]

PegIntron shows greater up regulation of IFN alfa response genes. Pegasys has a longer half-life from being linked with a branched PEG molecule.

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16780997&dopt=AbstractPlus

[Bobby1952]

What does that really mean? Does it mean that alpha-2b is more effective.

[desrt]

It means alpha-2b may do some things on a biochemical level more efficiently during the early part of treatment but since the drugs currently available have IFN alpha-2a linked to a better PEG molecule, the two products are equally "effective". You'll have to get HR or someone else to explain 'upregulation of genes'.
And don't ask why 'they' don't produce a Peg IFN with alpha-2b linked to branched PEG molecule, instead of fiddling around with protease and polymerase inhibitors I might start talking about international patent law and corporate greed.

[willing]

the wikipedia article on interferons might be a good starting point
http://en.wikipedia.org/wiki/Interferon

interferons are a class of proteins naturally produced in response to the detection of virus. They play a fundamental role in the immune response; though they don't directly interact with virus they trigger a wide-raging set  of changes that inhibit viral replication and kill infected cells. Injecting ifn amounts to supplementing the ifn naturally produced by your body with an external supply of synthetically manufactured but identical molecules (hence your body responds as if it's dealing with the mother-of-all-flus)

The body naturally breaks down and recycles its proteins. To keep the ifn "car-alarm" in circulation longer, synthetic ifn was modified by  addition of an extension (polyethylene glycol, PEG). Tethering this "canon-ball" like extension to the protein has no change on its signaling activity, but it does delay its break down. Hence peg-ifns only have to be injected once a week whereas non-peg ifn is injected a minimum of 3/week. There's a tendency to see ifn-based studies as "dated" relative to peg-ifn studies. Not so - addition of the peg is purely a patient-convenience factor (for example consensus ifn is not pegylated and is often injected daily).

Roche  claims one-size-fits all dosing (180 micrograms/week) for its product a claim that those weighing above a certain cutoff might want to question. Schering's product is weight based.  As best  I know this is the only significant difference between the two, though a  number of people on this board who have tried both have reported different side effects.

[jmjm530]

"There's a tendency to see ifn-based studies as "dated" relative to peg-ifn studies. Not so - addition of the peg is purely a patient-convenience factor (for example consensus ifn is not pegylated and is often injected daily).
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Willing, wasn't clear if the above is from Wiki, or your commentary. In any event, this large review of randomized studies seems to suggest otherwise. I also thought that Peg had been proven superior in the initial Peg trials, but maybe that is covered below.

"Conclusion: Pegylated interferon plus ribavirin compared with interferon plus ribavirin increased the proportion of patients with sustained virological response, but at the cost of more adverse events."

http://www.medscape.com/viewarticle/557838 (Free Mescape Registration Required)

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Also, re another topic -- frequent VL testing, some interesting comments by "Susie" re a well-known clinician/researcher. While I can't see I'm in certain agreement with him in this case, his contention is that the lack of early and frequent VL testing will affect the accuracy of predicting SVR Telaprevir prospects. In any case, if not in this instance, I think the more data we accumulate in this respect can only be a plus -- it not for the first treatment, but for perhaps future tx scenarios as per example Dr. S.

http://www.medhelp.org/posts/show/407302

[jmjm530]

"There's a tendency to see ifn-based studies as "dated" relative to peg-ifn studies. Not so - addition of the peg is purely a patient-convenience factor (for example consensus ifn is not pegylated and is often injected daily).
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Willing, wasn't clear if the above is from Wiki, or your commentary. In any event, this large review of randomized studies seems to suggest otherwise. I also thought that Peg had been proven superior in the initial Peg trials, but maybe that is covered below.

"Conclusion: Pegylated interferon plus ribavirin compared with interferon plus ribavirin increased the proportion of patients with sustained virological response, but at the cost of more adverse events."

http://www.medscape.com/viewarticle/557838 (Free Mescape Registration Required)

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Also, re another topic -- frequent VL testing, some interesting comments by "Susie" re a well-known clinician/researcher. While I can't see I'm in certain agreement with him in this case, his contention is that the lack of early and frequent VL testing will affect the accuracy of predicting SVR Telaprevir prospects. In any case, if not in this instance, I think the more data we accumulate in this respect can only be a plus -- it not for the first treatment, but for perhaps future tx scenarios as per example Dr. S.

http://www.medhelp.org/posts/show/407302

[mikesimon]

Peginterferon alfa-2a/ribavirin in HCV patients nontolerant or nonresponsive to peginterferon alfa-2b/ribavirin.
Rustgi VK, Esposito S, Hamzeh FM, Shiffman ML.

Liver Transplantation Unit, Georgetown University Medical Center, Washington, DC, USA.

Background: Peginterferon alfa-2a/ribavirin had lower incidences of depression and flu-like symptoms than standard interferon/ribavirin, whereas peginterferon alfa-2b/ribavirin and standard interferon/ribavirin had similar incidences of these AEs. Aim: To assess the efficacy and safety of peginterferon alfa-2a/ribavirin in genotype 1-infected patients treated for up to 12 weeks with peginterferon alfa-2b/ribavirin but not achieving EVR (non-EVR) or non-tolerant (NT) due to depression, fatigue, flu-like symptoms, or injection-site reactions. Methods: NTs were treated for an additional 36 weeks and non-EVRs for an additional 60 weeks with peginterferon alfa-2a (180 mug/wk)/ribavirin (1000/1200 mg/d). Patients with detectable HCV-RNA after 12 weeks were discontinued. Results: Of 25 NTs, 23 (92%) were HCV-RNA negative after 12 weeks on peginterferon alfa-2a/ribavirin and 14 (56%) achieved SVR. Of 32 non-EVRs to peginterferon alfa-2b/ribavirin, 4 (12.5%) achieved EVR with peginterferon alfa-2a/ribavirin and 1 (3.1%) achieved SVR. Four non-EVRs and 0 NTs were withdrawn for AEs; 26 (81.2%) and 24 (96.0%), respectively, completed peginterferon alfa-2a/ribavirin treatment or were withdrawn for insufficient response at Week 12. In NTs, depression, fatigue, flu-like symptoms and injection-site reactions declined during treatment. Conclusion: Most patients who did not tolerate peginterferon alfa-2b/ribavirin due to AEs and who completed the full 36-week course of peginterferon alfa-2a/ribavirin treatment achieved SVR.

PMID: 18081737 [PubMed - as supplied by publisher]

peginterferon alpha-2b plus ribavirin treatment in patients with chronic hepatitis C.
J Viral Hepat. 2007 Oct;14(10):721-9
Di Bisceglie AM, Ghalib RH, Hamzeh FM, Rustgi VK.

Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St Louis, MO 63110, USA. ***@****

Patients infected with hepatitis C virus (HCV) genotype 1 and with serum HCV RNA concentrations over 800 000 IU/mL have relatively low rates of virologic response to pegylated interferons. The 2 forms of pegylated interferon have different pharmacokinetic profiles, and pilot studies comparing them have yielded varying results. We compared the virologic response to 12 weeks of treatment with peginterferon alpha-2a plus ribavirin vs peginterferon alpha-2b plus ribavirin in 380 patients who were infected with HCV genotype 1 and had high viral loads. We observed no between-group differences in viral load reduction over time and no differences in the percentage of patients treated with peginterferon alpha-2a or peginterferon alpha-2b plus ribavirin who achieved early virologic response (EVR), defined as >/=2-log reduction in HCV RNA concentration or undetectable HCV RNA at 12 weeks (66%vs 63%). Serum levels of interferon were more frequently below the level of quantitation in patients treated with peginterferon alpha-2b plus ribavirin (58-68%) than in those treated with peginterferon alpha-2a plus ribavirin (1-2%). Patients treated with peginterferon alpha-2b plus ribavirin had higher rates of discontinuation for safety reasons (6%vs 1%). In conclusion, a substantial percentage of patients infected with HCV genotype 1 and high viral load can achieve EVR when treated with peginterferon and ribavirin. The 2 pegylated interferons showed comparable anti-HCV activity during the first 12 weeks of treatment when combined with the same doses of ribavirin (1000-1200 mg/day), but discontinuations for safety reasons were higher in the patients treated with peginterferon alpha-2b plus ribavirin.

PMID: 17875007 [PubMed - indexed for MEDLINE]

Mike

[jmjm530]

I know you like the more technical so you might want to continue searching. While no one can say for certain which is the "better" Peg, the molecules are different and so is the dosing scheme with Peg Intron dosed by weight and Pegasys with a one dose for all weight scheme.

You will also find advocates among leading doctors/reseachers for both in private conversations although the ones I've spoken to -- advocates on both sides -- admit their conclusions are somewhat anecdotal. For example, one of my consultants said that he found the vl response identical, but fewer relapses with Peg Intron. Another doctor I consulted with disagreed. Not surprisingly, each of these doctors ran trials for one of the respective Pegs. I was also told that Pegasys might favor me at my pre-tx weight -- 175 pounds -- while someone heavier -- let's say over 200-- might be favored by weight-based Peg Intron. But again, the studies show no clear favorites, not if closely scrutinized by both structure and sponsor.

And then there is the side-effect profile and anecdotal accounts that seem to favor Pegasys over Peg Intron although I'm unaware of any studies on this.

Personally, I treated with Pegasys because that is what my original NP advocated, also bringing up the side effect issue. That said, from what I've heard since, I probably would have treated with Peg Intron to do it all over again. Of course, I became SVR with Pegasys, so that might have been the wrong decison :)

-- Jim

[Myown]

To me plain and simple - as I mentioned once before,,if I had my choice I would do 24 weeks with one and the last 24 weeks with the other. I don't know why we can't do that? Has anybody asked their doctor to do that for them? I'm going to ask mine. I'm not having it shipped until end of feb, so why not ask,,,if he says no, I'll ask why not and I'll need to hear a good reason. If its because they didn't do a study splitting the 2 interferons - most doctors claim the interferons are the same,so it shouldn't matter to them if I feel better splitting the interferons. I'm the one with the virus. If its a money thing - too bad, lets the Pharma's split the pot if it will help someone svr OR get thru tx.

I was feeling fine about my choice of Pegasys because a member pointed out some things that made sense - but now I am getting a little shaky and I wonder if Pegintron should be used IF I CAN'T get a split. And I know some might think no way will you be allowed to use one for 24 and the other for the last 24, but if no one has ever thought to ask their doctor,,maybe they'll say yes - no problem. I mean really, IF I was sick as a dog last tx and taking Pegintron, I would have begged for Pegasys - not continued to be miserable or quit tx - why not try the other interferon mid way if a person was sick on Pegintron? I wonder how many people discontinued tx while on Pegintron instead of the doctor switching pegs. I'm going to ask my doctor if he ever switched pegs mid-stream for someone that was sick and IF not, why not?

[willing]

jim/all:  yes, in my post above I did not mean to infer that peg-ifn is comparable to the older 3/week ifn injections. Sorry if I wasn't clear. The superiority of peg in this regard has been documented extensively - basically, three times a week is not often enough to avoid the effects of breakdown.  My point is that the PEG contributes nothing to the protein's function. Hence studies that used daily ifn dosing, eg those relating to induction dosing or  consensus interferon are not "dated" or irrelevant  because they use ifn without the peg-add on.


mike - thanks for those refs. The verdict on the side-effect aspect seems mixed. As I recall you personally found 2b much more tolerable, though I believe some here reported the opposite. I've only experienced non-peg and 2a and detested them equally.

[moahunter]

I don't see the point in doing 24 weeks on one, and 24 weeks on the other, if you are responding to the first one. Seems to me, is all you are doing, is setting yourself up for additional side effects, as your tolerance to the first 24 week peg may not apply to the second 24 week. At some point, it all gets too unscientific if we say, do 12 weeks or this, 10 weeks of that, 5 weeks of this, etc. etc. Do the full course if it is working. If it fails, maybe the other will work for you.

PS. My own experience is that Pegintron has harsher sides, but, I was only on Pegasys monotherapy. Riba may be the really nasty drug in the mix IMO, it seems to be the reasosn so many need helpers and similar.

[Myown]

I don't see the point in doing 24 weeks on one, and 24 weeks on the other, if you are responding to the first one. Seems to me, is all you are doing, is setting yourself up for additional side effects, as your tolerance to the first 24 week peg may not apply to the second 24 week. At some point, it all gets too unscientific if we say, do 12 weeks or this, 10 weeks of that, 5 weeks of this, etc. etc. Do the full course if it is working. If it fails, maybe the other will work for you.
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My point is that last TX I DID respond (RVR) yet relapsed 8 weeks post.

I don't feel I am setting myself up for more SX, but more like "trying" to set myself up for SVR.

As far as at some point, it gets "too unscientific," well, "scientific" is not working that great these days so sometimes logic is better than science.

[Myown]

The smaller molecule with the Pegintron is what always gets me nervous. My doctor does believe the virus crosses the BBB.

[mikesimon]

No, it was just the opposite. I found regular interferon bad and 2b equally as bad with regard to side effects. The 2a was like day and night for me. I know that when I stopped Peg-Intron it was too early but I could not go on any longer. Then maybe 2 months later I was on Pegasys and I did 73 weeks without nearly the degree of difficulty that I had doing 52 weeks of Peg-Intron. I developed the same degree of hemolytic anemia but that was controlled with Epogen. Mike

[Myown]

Not "nervous," but "concerned". And if Pegasys can't reach the virons in the brain, thats my concern.

So I'll ask.

[moahunter]

I don't know Myown, whether one Peg has a higher relapse rate than the other. It must be tough to have been RVR, then to relapse. I am hoping it will not happen to me over the next few weeks (although I won't know one way or the other for 6 months, as PCR's are not readily available in Canada).

You may want to try some of the alternatives that others have done (longer treatment, using just the other peg, etc.) before speculating on mixing pegs. I guess medicine is as much an art as a science though, and as I am neither a doctor, scientist or artist, who am I to say? Good luck.

[Myown]

Yeah,I'm going 48 weeks this round. Ya know what? I am a control freak in a way - probably a big way and thats no good. Probably have a bad case of OCD - although I always thought it was a "made up disease," and haven't been dx, but then again I haven't asked any of my doctors for their opinion. lol So  anyhow, I look at everything and then change my mine 200 times and then I finally say "okay, I did what I could possibly do and can't do no more." But it takes me a long time to get to the place where I think I "did all I could do." So in short - I'm nuts, but my football lovin' husband loves me though..

Yes,it was hard to relapse after being RVR, but I had to stop complaining about that cause there are lots of other things that could be worse. Alot of members here have been thru and some still going thru alot worse, so I look at their testimonies and strength to help encourage myself along the way.

I wish you the very best and I so hope to hear that you are SVR.

Good luck moa, nice talking to you.

[geterdone]

Let me ask all something, are there any studies and/or research data available to date that may apply to a reversal of SOC close to the end of treatment. Let’s say, if one follows SOC, 180-peg INF, 1200mg riba for 22 weeks and then reduces riba to 1000mg from there to 44 weeks. All the sudden, stops INF but continues with the riba dosage until INF is obtained. The span between last injections until new injection is approx 18 days in which the elevated INF levels cascade downward to, and beyond the natural INF threshold accentually stopping all production of INF and because of this an imbalance and system shock has created an opportunity for existing or undetectable virions to restart the replication process again. Now, if in this time frame of INF imbalance which has caused chaos across all systems associated with fighting the virus, in which it may have actually started, what would be the best course of action at this point going forward?

I have been asking a lot of specific questions here as of late on a wide array of areas associated with the virus in the preparation of a what if, and have a fail safe plan in which to fall back on given the probability of an unfavorable out come of  the INF time laps.

Are there any Studies and/or Research Data available given this scenario?

UND since week 8

180-pegINF   x44 weeks
1200mg Riba x22 weeks
1000mg Riba x22 weeks
Abrupt stoppage INF week 44
Continuation Riba 2xan/3xpm
INF time laps 18 days
Extension time?

Thanks!
Jasper

[willing]

mike : thanks for the correction, actually I do  remember your posting that before and mistyped  2a and 2b...  Last time someone ran a 2a vs 2b sides comparison post 2a seemed to do better but as I recall there were also some 2b fans.

mo : if you're looking at anti-viral effect,  consensus ifn would probably be a better choice to investigate than 2a vs 2b. Re-tx with cifn has gotten some good results, see for example that aasld abstract 310 in the 72-week thread. On the other hand, in you're interested in  comparing side effects, that seems like an excellent plan!

[Myown]

Daily injections? No thankyah.  My doctors - the one I treated with last year thinks just extending will do the trick with the same peg - Pegasys.(geno 2b)

The new doc that I consulted with said Pegintron, but I was concerned about sx and he said okay to Pegasys, but now I'll talk to him and ask if I start with Pegintron will he switch me to Pegasys if I get sick- if I can't have a "planned split in tx." My point is that I would like the small molecule of Pegintron at least for a while, but I certainly wouldn't want to go on that Peg IF it was going to be a hard ride without knowing I could switch.

Willing, I'll wind up giving you a headache, if I haven't already. Run away from me while you still have the strength. Jim and mike may have already messaged you with those instructions. lol

Take care.

[jmjm530]

MO: I'll ask why not and I'll need to hear a good reason..
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"Because we don't do flaky treatments in this distinguished facility " :)

[geterdone]

Thank you all for the feed back on the difference between the two INF’s and may explain some internal things back early on in treatment. Thanks!

But I have one last question, and should know but am blank at the moment, what does INF-peg go after in the replicon chain and what does the Riba do and/or follow up on?

NSB5B - INF?
NS3 - Riba?
Or is it reverse?

jasper

[jmjm530]

Get: hat does INF-peg go after in the replicon chain
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Personally, I think this is the most noteworthy replicant in the entire Ridley chain:
:http://tinyurl.com/yryd72 although this one should also not be forgotten:
http://tinyurl.com/yrbt87

[Myown]

Because we don't do flaky treatments in this distinguished facility
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hardy har har. Its not flakieeeeeeee. I'll book mark this page so I can ~remind~ you that I had the idea first and didn't need to see a study to prove it was a good idea Jimmmmie.

That "distinguished facitilty" ain't all that:)