Understanding HCV Nonresponse and Identifying Candidates for Retreatment

[mikesimon]

A new Clinical Care Options article.

See:  http://www.tiny.cc/ilRHl

Registration is required but free and easy to do.

Mike

[Susie2007]

This is a really good CME on who may benefit from re-treatment and who will not. Dr. Shiffman is a great hep doc.

[susan400]

Thanks, Mike, for posting that.  Susan

[gauf]

Interesting. The article states that someone with a 2 log drop by week 12 can up the interferon.

quote"...it has been hypothesized that some patients with a partial treatment response can achieve undetectable HCV RNA if switched to a more intensive interferon regimen (Figure 6). The time at which to intensify the interferon regimen can be anywhere between 12 and 24 weeks.."unquote

I was under the impression that upping the peg initially (i.e.double dosing) is probably the best method to help achieve RVR or EVR.  Between weeks 12 and 24? did i read this right?

[mikesimon]

Yes, you read it right but, that approach is just theoretical at this point - according to the article.
"Based on these observations, it has been hypothesized that some patients with a partial treatment response can achieve undetectable HCV RNA if switched to a more intensive interferon regimen (Figure 6). The time at which to intensify the interferon regimen can be anywhere between 12 and 24 weeks. However, the patient must be able to tolerate the higher dose of peginterferon alfa and be motivated to continue with treatment. The major limitation to this strategy is firstly the accessibility of higher dose of peginterferon alfa to many patients, as it is unlikely to be approved by many insurance companies without more concrete data supporting this approach and, secondly, the increase in the discontinuation rates because of tolerability issues. In patients treated with a more intensive interferon regimen, HCV RNA should continue to be monitored at monthly intervals. If the patient does not achieve undetectable HCV RNA within 12 weeks of dose intensification, treatment should be discontinued. By contrast, if the patient does achieve undetectable HCV RNA, this treatment should be continued for an additional 48 weeks. This is the typical duration of extended treatment in patients with slow virologic response."

As stated there need to be more "concrete data supporting this approach". I believe that extending treatment duration has more supporting data for achieving SVR but the dose increase seems to also include extending treatment 48 week post undetectable so maybe it's the best of both worlds - if you can tolerate it and either convince your insurance co to pay for it or pay for it out of pocket. The increased dose and duration will be hard to get approved in my opinion. Mike

Mike

[gauf]

If one did have access to the increased peg, then when the optimal time to take it seems to be pretty important. It always made the most sense to me to take it early to help achieve RVR.  I wonder where the 12 to 24 wk idea came from. I mean even a hypothesis has to have some sort of data to formulate a good hypothesis.

[nygirl7]

As stated there need to be more "concrete data supporting this approach". I believe that extending treatment duration has more supporting data for achieving SVR but the dose increase seems to also include extending treatment 48 week post undetectable so maybe it's the best of both worlds - if you can tolerate it and either convince your insurance co to pay for it or pay for it out of pocket.


Right..  However - the problem with interferon is you can't see the damage that it's doing to you on the outside.  With an increased dosage of that stuff also goes the better chance that you will ruin your thyroid for life. Since those sides match the tx sides almost exactly...nobody finds out until they finally get a TSH pretty well into treatment.  Is it better to take a bigger dose for a shorter duration or a smaller dose for a longer duration?  Who knows.  I am just pretty sure that in my mind...extending gives you such a better chance at getting 'them all' that to me - it was worth it.

Also Mike I agree with your assessment - what I think he says above is - at week 12 up the dose then continue on for 48 weeks. So that would seem to me that you ARE going to be doing the larger more damaging (potentially) dose for the extended period anyway.  I wouldn't want to think of what kind of shape I would be in today had I done both - I'm barely a viable human being at this point 8 months post with the thyroid and the anemia just as bad as when some people treat in the first place.

[gauf]

The SX are really whats driving my curiosity. I kind of thought "Hit it hard and hit Early", and then when the sides come on, taper down to a level that allows extended treatment. The above approach almost seems like an opposite effect. Start SOC, then at 12 to24 wks.. Hit it hard. Seems the sides would really be rearing there ugly heads by then. Doesn't make sense but sense may have nothing to do with it.

[NYCMark]

My reading of the 12-24 week theory stated above is this: it really is ideal to START treatment with a double dose at week 1-12; but for all the other reasons above - insurance non-payment, autoimmune problems, early discontinuance, unacceptable side effects - then perhaps the NEXT best thing for those who are partial responders at week 12 is to increase the dose for those people at that time. If we knew who would be early responders, who would be partial responders, who would be null responders, it would be SO much easier to plan treatment.

Mark

[gauf]

Got that right. All I know is that I was UND at 12 wks and EOT. But I relapsed. I will allow myself to believe I was an EVR (although it is possible I was an RVR) when formulating my next round of treatment. I know going in from past experience that I will be anemic and maybe worse. I know i can persevere through severe sides on pure will power for quite awhile; but over time they will wear me down.

[gauf]

..and besides, why would insurance cover extra meds any more readily at 12 wks than at start of treatment?

[gauf]

I believe it was FLGuy who double dosed on peg. Wonder if he did it at start or later; and if SX got worse than SOC.

[FlGuy]

I did a couple of things.  Started full dose riba a week in advance and then doubled (Pegasys 180 x 2) for the first 4 weeks. Got to und. after week 2.  Starting vl was about 4 mil i/u..  The double peg was about 25% more sx than single peg.  Tolerable and do-able since I knew it was going to be brief.  Goal was to get to und as soon as possible and to be und for as long as possible for the duration.  Doc's benchmarks were und at 4 do 48, not und at 4 do 72.  G3 relapser.

[gauf]

Right. So at 4 wks you went to SOC. I too am around 4 mil and G3 relapser. Have you gone to 6 mos post yet?

[FlGuy]

I'm about 5 weeks post now.  Was und at 3 weeks post tx, but don't think that tells me a lot yet.  The 2nd tx was weight-based riba (1200), first time was only 800.

[willing]

it seems Shiffman updates his re-treatment survey on an annual basis but doesn't put that  much time into it. Some of the references in this edition are as recent as this year, but he doesn't seem to have tracked new results very closely. For example, if one looks on pubmed, there are lots of recent studies on induction dosing. Rather than falling back on "it has been hypothesized that " it would be more useful to dig in and make sense of what this new data is saying. In the case of dosage increases, the benefits don't  seem obvious.

[gauf]

it would be more useful to dig in and make sense of what this new data is saying. In the case of dosage increases, the benefits don't  seem obvious.
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Is this your opinion, or are is there evidence that dosage increases have no benefit?

[jmjm530]

Admittedly, I haven't been number crunching laterly, but my doc told me that double-dosing might help my chances of SVR around 10%, and if memory serves me -- I think a similar figure was stated over at Clinical Care Options on perhaps the Dieterich/Jensen video. It's been awhile. Video I saw was "Doc Eye for the Hep Guy" and dealt with re-treatment issues.

[gauf]

Well, 10% is 10%. I'll take whatever I can get. thanks Jim.