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

[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 Four non-EVRs and 0 NTs were withdrawn for AEs; 26 (81.2%) and 24 (96.0%), respectively, completed peginterferon alfa-2a/ribavirin treatment or were withdrawn for insufficient response at Week 12.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.