Relapse rates after Virus Undetectable Finding

[GetOffMyLawn]

I've been virus undetectable since week four of triple therapy with Incivek. I'm at week 37 now, but won't have anymore viral load test until I finish in eleven weeks. My liver enzyme levels quickly dropped to normal. I started between stage 1 and 2 liver damage
My liver specialist's opinion is that I shouldn't relapse, but I can't find anywhere stats to back up his optimism. I can't even find any long term studies of relapse rates on supposedly cured patients. Just rates for those six month out (when the consensus seems to be your cured). I know Incivek has only been around three years, but most of those involved in the clinical studies have been off the drug for two years at least. Anyone know what's happening to them? Is the data not available because nobody in the drug companies cares to collect it? After all they've got FDA approval or is the data just really hard to find? This secondary question isn't as important to me as the first. Should I be as happy as my doctor?

[HectorSF]

As pooh pointed out the issue of late relapse is not a serious issue with this or any new treatments. We know from published data that SVR12 when using Sovaldi based treatment is 99.8% a cure. Meaning only 0.02% will show virus at week 24. Whereas with all peg-interferon based treatments including 1st generation PIs a large percentage of patients never had the opportunity to relapse after stopping treatment as they failed the treatments while treating... by being non-responders, or having viral breakthroughs while treating. This doesn't happen with the never treatments.

Many of us have treated with these treatments in the clinical trials and are well  aware of how they work and the differences between these new treatment and older treatments. All of the data related to any treatment is available online for anyone interested. It is because of this data that we have progressed perhaps more quickly in the last 3-4 years than any other field of medicine.

Since progress has been so rapid our former Standard of Care (SOC) using peg-interferon and ribavirin and then the first generation of PI treatments while at the time all we had now seems archaic compared to what we have now and what will be here in the coming year. (But then again 5 years from now, these treatment will also seem like a Model T as well). Thankfully.

So now the AASLD and the IDSA do not recommend the the use of the first generation of PIs and one manufacturer (Vertex) has decided to stop selling the drug in the U.S. (Maybe they will still sell it to other countries that don't have access to Sovaldi based of other DAA treatments).

"Vertex Pharmaceuticals announced that it will stop selling its HCV protease inhibitor telaprevir (Incivek or Incivo) as of October 16, 2014. While the first generation direct-acting antivirals are more effective than pegylated interferon plus ribavirin alone, they are no match for newer drugs such as Gilead Sciences' sofosbuvir (Sovaldi) or AbbVie's forthcoming "3D" regimen in terms of efficacy or tolerability."

"We request that healthcare providers not start any new patients on INCIVEK at this time because of the discontinuation of the sale and distribution of INCIVEK. Vertex will continue to provide financial support to eligible patients currently prescribed INCIVEK and, for those currently under treatment, will address available drug supply needs to complete treatment regimen. For INCIVEK product support information, please contact: 1-877-824-4281."

Hopefully this will FORCE those who are responsible for paying to HCV treatments (whether health insurance companies or government entities) to approve the payment of more effective and safer new treatments.

The data for the use of peg-interferon and ribavirin and long term consequences are legion. That is why we and the pharma industry are trying to get away from having to use them.

As far as the first generation of PIs they are know to create resistance so people who treated and failed PI treatment were excluded from many trials because of this factor. The Sovaldi/Olysio COSMOS trials for example. While early trials didn't address this population new treatments are including these people so that people that failed Incivek and Victrelis treatments can be cured using some of the newer treatments. Treatments only continue to get better as time goes on for all of us.

Good luck with your treatment!
Hector

[GetOffMyLawn]

Thanks again for sharing your research and you're encouraging words. Since the study you reference covers just interferon based treatments, it's still an open question whether the new treatments are more effective in the long run. I certainly hope so. My provincial government is taking it's own sweet time adding the latest drugs to its formulary which means that only the very rich or those with incredibly generous health insurance can avail themselves of the new drugs. The best argument to get government subsidized coverage is that the new therapies permanently cure HepC. If even the new drugs have a significant relapse rate, this weakens our efforts to get these drugs accessible for everyone. Lack of such studies make the issue harder to resolve.
Since my first post of this topic I located Vertex's financial reports for 2012 and 2013. It reported net revenue of about 1,200 million for 2012 and 446 million for last year, just for the sale of Incivek. This means there are surely 20,000 persons who have been treated with Incivek (I've estimated that at least 10 persons are treated for every million in revenue). Yet the studies we are always referred to about SVR rates are those involving just a few hundred that were used to get FDA approval.
As you know, Incivek is going the way of the dodo in favour of new drugs, but the lack of follow up data seems systemic in Big Pharma, where long term side effects are often unreported for years.
Thanks for your time.

[pooh55811]

There was a study done and it is published. It looks like there were just under 3% of the people in the trial who had a late relapse (after attaining SVR).

"Relapse Long After Hep C Cure May Be a Dormant Infection"

"Those who relapse an extended period of time after achieving a cure for hepatitis C virus (HCV) may not have been reinfected with a different strain of virus, but may be experiencing a resurfacing of the original infection, Healio reports. Publishing their findings in The Journal of Infectious Diseases, researchers analyzed RNA sequences of hep C in both serum and liver tissue that were taken from 103 study participants who achieved a sustained virologic response (SVR, considered a cure) after receiving interferon-based therapy between 1985 and 2005.

Three people in the study group relapsed late, yielding a positive hep C RNA test a respective 8, 75 and 78 months post SVR. Then there were four participants who relapsed early; they served as the study’s control group.

Investigators sequenced serum samples from both before the participants began hep C treatment and after they relapsed. They found that there was a 99.4 percent sequence match between the two serum samples among the early relapse participants and a 99.8 percent match between the samples among the late relapsers. The strains of virus also had the same genotype between the sample pairs in all cases. The implication is that no new viral strain was introduced in the late relapsers.

The researchers state that the liver in particular can harbor hep C after an SVR. Further research is needed to determine how such low levels of viral RNA can persist for extended periods after a cure."

http://www.hepmag.com/articles/viral_relapse_2501_24808.shtml

That article has a link to the abstract.

Personally, I was tested at 1 year post EOT and I was UND. I was just tested again (2 years post EOT) but I don't know the results yet. I am assuming it will be negative but, obviously, I wanted to know for sure because I had the test done.

I can tell you that we (the forum) had several previous Null-responders on Triple Tx with Incivek and they did attain SVR. One had Cirrhosis and he still attained an SVR. So here's hoping that you will also attain SVR.

[GetOffMyLawn]

Thanks for your reply.
This my second try at thx. I was a null responder. Ten years ago. Never told if was Genome 1a or b. It may be in my chart, but that part has been archived.
I've read the studies you've referred to or similar ones. None of those studies  do follow up testing after 6 months. There are lots of people who completed thx years ago, and I'm sure they're tested, But my point is no one seems to be publishing this data. Do ten per cent relapse? Twenty? Or hopefully zero. Knowledge is power and I can't seem to find this info.
P.S. Yes my eRVE was greeted with big smiles from my treatment team.

[pooh55811]

Welcome to the forum.

"I've been virus undetectable since week four of triple therapy with Incivek."
"My liver specialist's opinion is that I shouldn't relapse, but I can't find anywhere stats to back up his optimism."
---------------------------------------------

You do not say if you have ever treated before and, if you treated, what the outcome was (relapse, partial responder, non-responder, breakthrough). That fact would be helpful to know. You also do not say if you are Genotype 1a or 1b. 1b is easier to cure than 1a.

If you have never treated before you have an excellent chance for SVR. However, you are doing 48 weeks of treatment and that leads me to believe that you were a previous partial or non-responder or that you had a viral breakthrough during previous treatment. If so, then your chances for SVR are lower than if you were treatment naive or a previous relapser.

First of all, you attained an eRVR (by being Und at week 4 of treatment). That fact is an excellent predictor of a positive treatment outcome.

Second, your liver fibrosis stage is fairly low-moderate. Having Stage 3 or Stage 4 liver fibrosis statistically lowers the chance for SVR. You are at Stage 1-2, which is good.

There are some statistics for SVR rates from the studies.

In the Advance trial: Overall cure rates for treatment naive patients on triple treatment with Incivek were 79%. For those who  attained eRVR (Und at week 4) that cure rate jumped to 92%.

However, the SVR rates dropped for treatment experienced patients. Prior Relapsers 86%, Prior Partial Responders 59%, and Prior Null Responders 32%.  See the Illuminate study results (which are just below the Advance study results) in the link I will post at the bottom of this post.

Being eRVR you do have an excellent chance for SVR. There have been many on the forum who attained SVR with triple med treatment (with Incivek) and many of those had been previous treatment failures. So you have an excellent chance for SVR.

Personally, I treated with triple med treatment with incivek. I did not attain an eRVR so i had to treat for 48 weeks even though I was treatment naive. I finished treatment 2 years ago and did attain SVR 18 months ago.

One of our members, Frijole, made a spreadsheet for many of us who treated at the same time. Go to her profile page and click on the white sheets. You will see all sorts of data on the sheets and the outcome of treatment. You will also see that most of us did attain SVR.

http://www.medhelp.org/personal_pages/user/223152

Here is a link to the studies I mentioned above.

http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm256328.htm

Best of luck. Please let us know when you attain SVR.

[hoping4cure]

The cure rate is pretty high for people that are F0-F2 that weren't treated before. Here's an article the has some info. Pretty risky treatment for those that were advanced as was I when I took the treatment.

http://www.aidsmap.com/Triple-drug-HCV-therapy-comes-with-high-risk-of-serious-adverse-events-for-people-with-cirrhosis/page/2642915/