Tapering off the Interferon and Ribavirin at the EOT?

[geterdone]

There seems to be a renewed interest in the Tapering off the Interferon and Ribavirin as some are getting closer to the EOT or are in the planing stages as to what to do. Most are aware that being on these meds for so long that the body had become adapted to the higher than normal levels of the interferon in the body and are concerned about when treatment is stopped what will be the lasting effects if any, after stopping abruptly. Also what will be the effects of the reversal or abrupt stoppage of the Ribavirin.

This has been discussed many times before with a lot of pro's and con's as to it's validity, of this unspoken controversial option. I think it is worth  revisiting the subject again as more people are aware of the personal options to them in how to deal with the aftermath of treatment. "To me understanding this process one needs to understand the process of the meds in the body at the beginning of treatment to see the possible benefits at the end of treatment." This thread should be a good base builder for those looking for the best course of action knowing what they have been through personally while on treatment and a furture base for those looking for such information.



jasper



1. What would be the best way to stop the Interferon?

2. What would be the best way to stop the Ribavirin?

3. Taper both together?

4. taper just the INterferon?



  

[Andiamo1]

Dr D contracted HCV from a needle stick and did walk the mile.  He is a very compassionate man and reads voraciously. I always found him to be more aware of the difficulty of treatment than any other doctor I used.

[Marcia2202]

I was under the impression that tapering would be beneficial to the body to get back to normal in a more gradual way, instead of going cold turkey. And feeling really sick post treatment. Please correct me, if this is wrong...

Marcia

[Trish77]

Personally, I am intensely interested to know what the impact of suddenly stopping interferon has on the body psychologically.  For me personally, I was able to manage without AD's throughout treatment and managed my treatment very well from a QOL and mental standpoint.  Then post-treatment, I found myself sinking into a depression so bad that I had to literally hang on with my fingernails and put out pictures of my kids around the house to remind me of my responsibilities so I'd keep fighting.  When I finally posted here how I was feeling, I was amazed at how many people posted that they too had suffered depression post-treatment.  It didn't come on right away, I would say...two weeks post treatment.  And then I started sinking badly.  Really makes me wonder if, for some of us, the body does not revert well from many months of constant INF to none and that there IS some sort of withdrawal process for a number of us.

Now I'm starting to feel better.  I started AD's and I have no idea if they're working.  I've been battling very hard to overcome this depression and really, I don't think they're helping.  I think it's simply all the mental work I've been doing and forcing myself to fight back and go through the motions.  I've battled hard every day to push through the darkness and reach for the light. The appendix surgery really knocked me back too and then my three adult kids being home for Christmas was really what shook me out of it.  I saw these wonderful kids around me and saw that I'm not a complete utter failure and saw how much effort they're putting into their own lives and it reminded me that the most important thing in the world to do right is what I see in them and how much they love me and look to me and I've rallied back.  They deserve so *much* from me.  I went for my first run in nearly a year last Sunday and again today .. not much.. 3kms each time...but I'm on my way back.  I feel much better physically and everybody tells me I'm looking great and that they REALLY notice a difference.  (I had no idea how BAD I've looked, apparently!  lol :)  Mentally, I'm still battling back but not nearly as dark as it has been.  I'm just still not..."me" .. but I'm continually working on it.

I would really like it if nobody had to go through that kind of darkness post treatment.  It's worth discussing and I wish there was more data on this.  I'm going to talk to my pscyhiatrist about this, since I'm lucky enough to have a psychiatrist on my treatment team who specializes in the effects of Hep C treatment.  

And I'm sorry if that was too much information.  It just happens to be the truth and if it helps somebody, all the better.

[Proactive]

I had this handy.
*"Interferon-β
Different turnover rates of hepatitis C virus clearance
by different treatment regimen were also described using
interferon-β.18 The treatment efficacy in patients infected
with HCV-1 was significantly higher with twice daily i.v.
administration of 3 MU interferon-β compared with once
daily i.v. administration of 6 MU interferon-β. After the
first injection peak levels of interferon were more than
two times higher in patients who received 6 MU compared
with patients who received 3 MU. After 4 weeks of
treatment serum interferon levels were similar in patients
treated with 6 MU qd and those treated with 3 MU bd. In
addition, the 2’-5’ oligoadenylate synthetase activity in
serum between day 0 and 28 was similar in both cohorts,
indicating that the observed difference in initial viral decline
cannot be attributed to differences in 2’-5’ oligoadenylate
synthetase activity. A significant reduction of platelets
and serum albumin together with a marked increase in
serum aminotransferases and a high incidence of renal
toxicity (proteinuria), however, appears to limit twice daily
administration of interferon-β.18
*Pegylated interferon-α
The elimination half-life for unmodified interferon-α
ranges from 4 to 10 hours, with peak serum concentrations
occurring at 3 to 8 hours following subcutaneous administration.
Thus, current antiviral treatment regimens
require frequent administration of standard interferon-α
with intervals ranging from three to seven times per week
for periods of 24 to 48 weeks. Twenty-four hours following
administration, there is little or no detectable interferon-
α remaining in the serum.19,20 An increase of serum
HCV RNA can therefore been observed on treatment-free
days in patients receiving standard interferon-α three
times a week.10,16
Polyethylene glycols (PEG) are amphophilic polymers
with varying average molecular weights that can be chemically
linked to proteins. Modification of proteins with
PEG has resulted in decreased clearance, increased serum
half-life and reduced immunogenicity for a number of
proteins.21 Peginterferon is synthesized by the chemical
conjugation of a PEG molecule with an average molecular
weight of approximately 40 kDa or 12 kDa to interferon-
α2a (peginterferon-α2a) or to interferon-α2b (peginterferon-
α2b), respectively. The size of the PEG moiety results
in sustained delivery and reduced clearance providing
the possibility of once weekly dosing.22,23 While
oszillations of serum HCV RNA are typically seen in patients
treated with standard interferon-α, an intermediate
increase of the viral load was not observed in the majority
of patients treated with peginterferon-α2a.16
Treatment of patients with chronic hepatitis C with
peginterferon-α2b (1.0 μg/kg qw) for one year doubled
sustained virologic response rates compared with a standard
regimen of 3 MU interferon-α thrice weekly for one
year (24% vs 12%).24 Peginterferon-α2a (180 μg qw) was
associated with a higher end-of-treatment virologic response
at week 48 (69% vs 28%) and sustained virologic
response 24 weeks after the end of treatment compared
with unmodified interferon-α given three times per week
at a dose of 6 MU for 12 weeks followed by 3 MU for the
subsequent 36 weeks (39% vs 19%).3
The second-phase but not the first-phase initial decline of
serum HCV RNA appears to be faster for patients treated
with peginterferon-α (in particular for genotype HCV-1 infected
patients) than for patients treated with standard interferon-
α, although statistical significance was not achieved.16
Such an increase may be due to an enlarged death rate of infected
cells during therapy with peginterferon-a but can also
be explained by the elimination of oszillations in the initial
decay of viral load in patients treated with peginterferon-α.16
Ribavirin
The synthetic purine nucleoside Ribavirin rapidly enters
eukaryotic cells and after intracellular phosphorylation exhibits
virustatic activity against a broad spectrum of DNA
and RNA viruses.25 Several studies have been conducted to
evaluate ribavirin monotherapy in daily doses of 600-1,200
mg in the treatment of chronic hepatitis C.26-28 While all trials
consistently showed a decrease in aminotransferase levels,
no virologic end-of-treatment responses were observed.
Moreover, the effect on aminotransferase levels was not
maintained after the drug was discontinued.
The antiviral mechanisms of ribavirin in patients with
chronic hepatitis C are unknown. Quantification of viremia
revealed either a minor decline or constant HCV RNA levels
after 3-6 months of ribavirin monotherapy compared with
pretreatment values.26,27 Two studies investigated the initial
antiviral effect of ribavirin (1,000-1,200 mg/day) in patients
with chronic hepatitis C.29-31 In the study by Lee et al. with
daily sampling within the first week of treatment, a less than
0.5 log or 0.5-1.0 log decline in serum HCV RNA was observed
in 5 and 10 patients, respectively, with no apparent
difference to untreated patients.29 Changes in HCV quasispecies
according to single-strand conformation polymorphism
band pattern within the initial four weeks occurred in only
one patient treated with ribavirin and in three of the untreated
patients. In the study by Pawlotsky et al., in which serum
samples were obtained even more frequently within the initial
treatment days, a mean decline of 0.3 log in serum HCV
RNA was observed at day 2 in 6 patients treated with 1,000-
1,200 mg ribavirin.30,31 Subsequent analysis of this study revealed
that the decline in viral load between ribavirin and untreated
patients achieved statistical significance."

[Marcia2202]

Thanks for sharing your experience. I had no idea that it has been THAT BAD for you. I'm sorry you have to go through this.

I personally do not find it too much information, but I find it very valuable information and one more reason to consider tapering off.

[Myown]

I know this is the type of discussion that sometimes causes debates, so I asked privately being it has been discussed already, but in seeing the thread, I am glad Jasper did post public in case there are those that never heard of the taper and want to discuss it with their doctor. Thanks Jasper. Jasper, I had asked you because I thought it was you that tapered. Maybe it was "Cruelworld" now that I think about it??

The abrupt halt of tx has always disturbed me and if I could find the post, I remember mentioning it didn't sit right with me before I ever even saw discussion on tapering.

As far as studies,I think(?) HR posted a study that I think was done in 1999? And it showed that SVR percentage rate was higher for those that tapered. If anyone has that study handy, maybe they could post it. I may have saved it. I will look if I can later.


Okay, my reason that I want to taper is that while we are injecting Interferon, our white cells are getting lower and lower, so are other things that are part of OUR NATURAL immune system.

When we abruptly stop Tx, we notice how low these counts went down. Within sometimes weeks, we see our white cells and other counts rising. As a matter of fact the doctors that don't know to use helper drugs DURING tx will cut interferon dose if the whites are too low, just so they can rise again. We know cutting dosage "during tx" can risk chance of SVR, but slowly cutting or tapering after tx, could it benefit?

So my feeling is that IF we taper slowly, we are buying time in letting our cells rise and our immune system strengthen, while still keeping the safety net of a little bit of interferon present. But being its not full dose interferon, as I just mentioned - our whites etc start to make a come back or whatever they do. Many have SVR'd without tapering but for some - they may need it - who knows??. Thats something to discuss with their doctor.

For me, I need to do it for MYSELF - just because I feel I have to try different things being the first tx didn't work for me. I would not tell or push it on anyone else, because I think its all how you look at it, until more studies are done. But as far as I am concerned - for me - its more of a gamble NOT to taper, being the other way didn't work for me and who knows what the reason was. They can sell that line "you fell into the small percentage of g2's" but that doesn't interest me. It may take more that just upping the dosage and extending the tx length and so thats why I am tapering - for my own mind or sanity. If I fail tx again, I won't blame the taper. But if I didn't taper and failed again I know I would be mad at myself that I didn't taper.


For those that remember my case, my virus didn't come back with a vengence. I was 4 weeks post UND AND at 9 weeks relapsed - but the virus was only 87,000 and that is very low for ME. So one theory I have is that I was stuck in a TH2 mode and the other is that my immune system was  just to low(white cells etc) to stop the replication.  


Also I wonder if the Pegasys totally lowers our immune system which to me would mean, its not 'helping' our immune system or 'assisting', but its over -riding it?
And if it is "over-riding it," or to some degree over riding it, then we would need 'resurrection time" of our own immune system. Its just too complicated for me, but I can't keep the questions from popping in my mind.

But anyhow, though I am one to want to know if I am clear at 4 weeks post. Part of me says to wait until 6 months because, though I would be happy to be 4 weeks UND, it didn't matter much in my case first round cause I relapsed anyhow, so I don't know what will cause more anxiety getting the early test or waiting. If I feel sick after tx, of course I would get one early, but if not, maybe its better to wait. Though waiting doesn't sound like me. I would probably do a test every 20 minutes post tx if they had home tests.