is triple therapy (incivek) the right prescription?

[OC]

I'm genotype 1a and was a non responder in 2002, I took peg/intron A (scheering-plough) with ribavirin.

Now my hepatologist is prescribing the triple therapy (pegasus - ribavirin) with incivek.

My question is, if i failed on peg/intron A with ribavirin before is this the right prescription?

thanks!

[Aeschines]

It appears when I resume treatment in Jan 2014, that I will be able to use the new drug 'Sofosbuvir'... or will I? I see where FDA approved the drug on Dec. 6, 2013. (See Post below) Does that mean physicians will be able to prescribe it now?


http://hepatitiscnewdrugs.blogspot.com/2013/12/hepatitis-c-gileads-sovaldi-sofosbuvir.html

The drug's webpage titled "Summary For Basis for Approval And Highlights for Prescribing Information" states the following:

"SOVALDI efficacy has been established in subjects with HCV genotype 1, 2, 3 or 4 infection."
And, under a study for genotypes 1 or 4 it says:
" It is estimated that the response rate in patients who previously failed pegylated interferon and ribavirin therapy will approximate the observed response rate in NEUTRINO subjects with multiple baseline factors traditionally associated with a lower response to interferon-based treatment (Table 9). The SVR rate in the NEUTRINO trial in genotype 1 subjects with IL28B non-C/C alleles, HCV RNA >800,000 IU/mL and Metavir F3/F4 fibrosis was 71% (37/52)."

[ceanothus]

I agree with Pooh (I always do!). From what I've read, it takes 18 months for the virus to fully revert to the wild genotype, so while the current tx would have a decent chance of working at that time, by then the newer drugs will either be approved for your situation, or will be only a few months away from approval. Good for you in confronting your doctor with the truth of how he screwed up! I sincerely hope it upset him enough to make him rethink his procedures and start being more careful. You may have just done something that will help many future patients!

[Aeschines]

Thanks pooh55811. I forgot about you when I directed my last post. You are great. I agree with your opinion. I will just put myself in UCSD's  hands and follow their instructions on future treatment. Except I will watch them also. From now on I am checking everything with research tools, this list and any other source of knowledge. Bottom line: we are responsible for  our treatment decisions.

[pooh55811]

If I was you I would not try to treat again with the Interferon, Ribavirin, and the Incivek (or the other Protease Inhibitor, Boceprevir).

Keep in mind your were a non-responder twice in the past. Some previous non-responders did treat with Incivek, Interferon, and Ribavirin and did achieve an SVR. However, several did not. Their chances were not as good going into the triple med treatment regimen. You treated for 24 weeks and then relapsed. You probably have resistant strains right now. You would have to wait for those resistant strains to return to a wild type virus. That would take many months. Even then, I doubt the doctors would retreat you with the same regimen.

You will be seeing a reputable Hepatologist soon. He/she should be aware of all of the new meds in the pipeline and those that will be approved fairly soon. He/she should also be aware of the clinical trials going on. New meds should be coming soon, in late 2014 or early 2015 (for people who treated previously). If it was me, I would wait for the new meds. I would not try to retreat for 48 weeks with the same treatment regimen I had already tried (even though it was cut short by your doctor).

Several meds are in the pipeline. The FDA has reviewed the Sofosbuvir and Ribavirin for Genotypes 2 and 3. The FDA has also reviewed the Interferon, Sofosbusir and Ribavirin for Treatment Naive Genotypes 1, 4, 5, and 6. These are the meds which may be approved as early as December of this year.

Initially these meds will not be available for people who have treated and failed. However, several medication regimens for treatment experienced (those who have treated before) are currently in trials and they are having very good success rates from those trials. Some of these medication regimens should be available for the treatment experienced late in 2014 or early 2015 if everything goes as anticipated and the drugs are approved.

According to the information I have read, the new regimens have fewer side effects than the current regimens and the treating time is shorter. I think I included some links in some of my previous posts.

[Aeschines]

The new treatments coming out next year. Who are they especially designed to help.  I also heard from my PCP they were easier to take. Any comments?

[Aeschines]

(So sorry for the length of this email but you should know and no response is necessary).

FYI, I went to see my ex-treating physician today and it was very depressing. When I asked him why I, as a two-time non-responder, was treated for only 24 weeks, he first said because he was adhering to the protocol from the company Incivek. He then pulled out a copy of the Incivek Protocol and commenced reading it to me. Then he showed me where his treatment was correct because 24 weeks is for patients who are "Treatment Naïve" or who have "Prior Relapses". Then I reminded him (me an attorney reminding a physician) that I was not treatment naïve, nor did I suffer a prior relapses, (I am sure you know that a "relapse" is one who was at 0 virus at the end of treatment and then the virus comes back. In fact, I am a relapse now, after my 24 weeks of triple-therapy treatment in 2012.) I am a 'non'- or 'null responder', which the sheet he gave me said required 48 weeks of therapy (for prior partials and non-responders.) He then told me he was not made aware of that info, from he wanted to say you all at Nh, but stopped. I then told him that, in my opinion, since he was the medicine dispenser (treater), he should have asked the right questions to see how to treat with the medicine. He started looking through my file and read that; in fact, I had told in June 2012 that I was a non-responder in 2000, or 2002. I think he said 2002. As you know, actually I was a non or null-responder in both years. So he had it in the records, (Please be sure when you get my records from him they so state this in an entry from June'12). After this, I continued to explain that why I was a non- or null responder and not a relapse because after 12 weeks of double-therapy treatment in 2000 my viral load was 200,000 IU and after 12 weeks of double-therapy treatment in 2002 my viral load was 150,000 IUs, he stated that that was low ... he was try to argue maybe I was a relapse, but again he caught himself. I just told him to send my PCP my records. He then, went into the "they may get lost spill" and asked if I could wait and take them. I waited around for a minute, and I then begged off and told him I did not want custody of the records. He asked why and I said I just do not. I will I do not think I will feel better until I get to UCSD Hepatology Dept. for which I have an appointment in January and we start treatment, whatever it is.

Say Guys. I was reading the Incivek literature (from ole’ doc) and two things I did not understand:

1. It read, Incivek efficacy has not been established for patients who have previously failed therapy. With a treatment regimen that includes Incivek, or other HCVNS3/4A protease inhibitors

Does this mean I can be treated again with the triple therapy, esp. since it could be argued that I am not a pure failure.. it was a doctor failure?

[Aeschines]

Thanks you and  pooh55811 are Great!. But the whole forum is great. I will keep u all updated on my next Nov. doctor's visit  (to doctor who we think screwed up), and how long it takes me to get back to UCSD.

[ceanothus]

NSAIDs are a whole class of drugs called Non-Steroidal Anti-Inflammatory drugs, and it includes all of the following:
aspirin Salsalate (Amigesic)
celecoxib (Celebrex),
diclofenac (Voltaren),
etodolac (Lodine),
ibuprofen (Motrin),
indomethacin (Indocin),
ketoprofen (Orudis),
ketorolac (Toradol),
nabumetone (Relafen),
naproxen (Aleve, Naprosyn),
oxaprozin (Daypro),
piroxicam (Feldene),
sulindac (Clinoril), and
tolmetin (Tolectin).

Acetaminophen (Tylenol) is not an NSAID. It is the only over the counter pain med that is considered safe for people with cirrhosis, as long as the daily dosage is kept to 2,000 mg per day or less. Ironically, it is one of the most dangerous to the liver in cases of overdosage, so be careful of the total dosage. It is added to many combination remedies, so one has to keep totals of the amount in each of the different sources. The overdose danger with Acetaminophen applies to everyone, but the warnings against NSAIDs are really oriented towards those with serious liver damage and if your liver is still in pretty good shape you might not have to worry over modest use of NSAIDs. I just like to warn people because some are prescribed large doses of them for arthritis or for back problems, and that in itself might accelerate liver damage from HCV, and in combination with even modest amounts of alcohol it is nearly certain to cause problems. I'm pretty sure it contributed to rapid progression to cirrhosis in my case.

[Aeschines]

NSAIDs  are acetaminophens, right? Do they include Ibuprofen and Aleve class pain meds (I forget he tech name) drug?

Yes, I will have to wait and I think my liver is in good shape. My doctor said I have some scarring but not much. Again, I can just thank GOD because I do not know why. I eat well, and do not drink alcohol (since I was diagnosed in 1994.)    I feel so blessed for you guys because if I hadn't stumbled onto this site I would continue to be treated by my current doctor, who I will see for the last time on Nov.12 when I seek an explanation for the 24 weeks vs 48 weeks. Then, I am going back to UCSD where my treatment began 10 yrs. ago.

[Aeschines]

Great Work Pooh. That one is right. I was treated at that liver clinic in 2003-5  (before my insurance ran out), and, as I said when I identified the  code & exchange as in Hillcrest,  that great liver center is in the UCSD facility in Hillcrest.  Also the 200 W Arbor Drive  (Hillcrest) San Diego, CA 92103 is Martinez's address also, and the phone # you gave for his is correct.  The only minor error was Gish's address should be Martinez's and the '858' number does not go with Arbor Dr., but goes with the La Jolla address I gave which was 9350 Campus Point Dr. La Jolla, CA 92037.  

When I treated there in 2003-05, Dr. Tarek Hassenein was in charge of the Liver Clinic. He did my biopsy. He used to leave and go speak on Hep-C all across the country. Have anybody heard of him? (PS I did a typo for his ph. #. His number should same as Martinez.)

[pooh55811]

I got that information on line by googling Dr. Gish's name. His name does not come up on the UCSD Health System website. That is why I am not so sure if he still treats people.

This one for Dr, Martinez:

Dr. Anthony Martinez
UC San Diego Health System
Liver Center:  619-543-5415

I took it right off of the  UCSD Health System website.

http://health.ucsd.edu/specialties/gastro/areas-expertise/liver-center/Pages/liver-center-team.aspx

Maybe it is outdated. I do know that the forum member who treated with them did so in 2011, so perhaps they are no longer there.

You live near there so you probably know more about the numbers than I do. I hope you find a good one. I would think the UCSD would be a good place to start.

[Aeschines]

I am not a Mr. Know it all, but I think the addresses and/ or tel #s are wrong on these physicians. Both appear to practice at UCSD, a large Univ. Cal hospital in San Diego. The W. Arbor Drive address is in a neighborhood called 'Hillcrest' where UCSD has a large med center. The UCSD facilities there (I was treated at both) has the 619-543 area code & exchange.  The '858-657' area code and exchange in in the north, main, campus located at: 9350 Campus Point Dr. La Jolla, CA 92037. Hope this helps for future.

But I understand and will sort it out.

[ceanothus]

There is an older thread here titled "Who is your good doctor?", wherein people were asked to write about who they thought was good. Here is an appropriate recommendation for you:

*************
We have two, both exceptional.  Our primary hepatologist, is Robert Gish at UCSD, in SD, and the doctor we deal with on a day to day basis is his partner, Dr. Anthony Martinez.  Dr Gish is usually off traveling around the world speaking about liver disease, but continues to respond whenever we need him.  Dr. Martinez has been the most extraordinarily responsive and knowledgeable doctor I've ever met.  I know how fortunate we are to have two hepatologists treating my husband when it's so difficult for many to find even one.  
*********

The entire thread can be found at http://www.medhelp.org/posts/Hepatitis-C/Who-is-your-good-doctor-/show/1715783.

I'm afraid I can't think of any other treatment options that would currently be available (without some waiting time first). You can take a look at what clinical trials are currently being run, in case there is something new that I don't know about. Info on clinical trials can be found at:
http://www.clinicaltrials.gov/.

In most cases waiting for a year or two to treat isn't any problem with this virus, as it generally progresses quite slowly. If we had some recent biosy results for you we could be more sure of that, but it sounds like your liver is probably not yet very damaged. I acquired the virus in 1984 via a transfusion, and was diagnosed around 1990. I first treated unsuccessfully in about 1990. Unfortunately, I was a slow learner in adopting a healthy lifestyle, so I continued moderate use of alcohol and heavy use of NSAIDs for my autoimmune arthritis, both of which are very hard on the liver. In 2004 I was diagnosed with cirrhosis. I immediately stopped all alcohol and all NSAIDs and started treating for the second time, which was also unsuccessful. When the protease inhibitors were approved in 2011 I started my third tx, with Incivek, for 48 weeks. Because of my history of failure, and because this was likely my last chance to treat before becoming decompensated, my hepatologist did not even consider lowering the dosages of the interferon or ribavirin even though I was anemic through most of the tx. He was going to prescribe procrit if my hemoglobin dropped below 10, but it never quite went below 10.3.  I finished tx 13 months ago and achieved SVR, finally.

Do be sure to avoid any alcohol and don't take NSAIDs either if you can help it. When you get a new hepatologist you can run all medications past him/her before taking them.

[Aeschines]

The doctor that first treated me, and who gave the liver biopsy was at the same address as Dr. Martinez & Gish. Maybe he trained them or vice versa because at the time (approx. 2004) he was considered an authority in the newly developing treatment for Hep C. Maybe you heard of him. This was his 2003-5 contact info: (it is same),

Dr. Tarek Hassenein
200 W Arbor Dr, San Diego, CA 92103
Phone:[phone]

Thanks.

[pooh55811]

" What do you think  is my chance of success  with a re-treat of triple therapy with Incivek if I wait 18 months, i.e.,  until the virus reverts back to its wild stage, and treat then, as Oceanus says may be an option. "
------------------------------------------------

That is very difficult to know.

The problem is, you did not treat for the recommended length of time with the treatment you just did, the Interferon, Ribavirin, and Incivek. Therefore, no one knows how you would have responded if you had treated for 48 weeks. You very well may have cleared the virus and now be cured if you had treated for 48 weeks. Other previous non-responders, even Cirrhotic non-responders, have been cured with 48 weeks of triple med treatment. Also, you did not clear the virus until 12 weeks so you were a slow responder on treatment. I would have been concerned about lowing drug doses in a slow responder. (I know you said he lowered your Incivek dose, but I hope you meant Ribavirin dose as Ribavirin is the drug that may be lowered in cases of anemia. Incivek dose is never lowered for any reason.) There is a possibility that you may have failed treatment even with the 48 weeks of treatment. This we will never know because your doctor cut your treatment short.

I mention all of this because we just don't know if you failed treatment due to a shortened treatment course or if you failed treatment because of genetic factors that made you more difficult to treat in the first place (Genotype 1a, race, IL28B type, interferon insensitive, etc.). If you would have failed treatment even doing 48 weeks, then there would be no point in retreating with the same drugs. You very well could be Interferon insensitive (you did fail 2 previous treatments ... non-responder). In addition, I don't think any Hepatologist would even consider retreating you with the same drugs. So, while technically if you showed no resistant variants in 18 months (and you would need testing for this),  I suppose one could technically retreat with the same drugs, but I just don't think any Hepatotlogist is going to do that. It is not recommended. They would be much more inclined to treat you with the new classes of drugs or get you into a trial.

The good news is that hopefully soon there will be new drugs of a different class that will not include Interferon. When I say soon, I mean possibly in 2015.
That would be Sofosbuvir, Ledipasvir, and Ribavirin. Plus there are other companies who are also testing some other drug combinations in other classes that do not include Interferon.  I do think treating with the drugs in another class may be your best option (as soon as they are approved).

There are some good Hepatologists in San Diego. Here is the name of 2 top notch Hepatologists in San Diego:

Dr. Robert Gish
200 W Arbor Dr, San Diego, CA 92103
Phone:[phone]

or

Dr. Anthony Martinez
UC San Diego Health System
Liver Center:  619-543-5415

I am not sure that Dr. Gish still sees patients but his partner, Dr. Anthony Martinez, does. He was the doctor for one of the forum members and was very highly spoken of. This is what she said about Dr. Martinez:  "We have two, both exceptional.  Our primary hepatologist, is Robert Gish at UCSD, in SD, and the doctor we deal with on a day to day basis is his partner, Dr. Anthony Martinez.  Dr Gish is usually off traveling around the world speaking about liver disease, but continues to respond whenever we need him.  Dr. Martinez has been the most extraordinarily responsive and knowledgeable doctor I've ever met.  "


""You come back and we have a couple of options:, He seemed to have some idea on his mind, i.e., not just a general we will wait and see. I know this is a heck of a question, but does anyone know what he may mean? "
----------------------------------------------

There is no way to know what he had on his mind. Maybe he was talking about the new treatments. Maybe he had no clue. There is no way to know. Regardless, I think you will have a much better treatment experience and outcome with a new Hepatologist who knows the proper medication protocols.

Best of luck.

[Aeschines]

1. As I said, I have an appointment to see my doc that stopped my treatment at 24 weeks & reduced my Incivek on Nov. 11. I will most definitely ask him about his decisions in my treatment, AND I am searching for a replacement. How can I find a good hepatologist in San Diego CA area? Anybody know one?  I have already asked my primary care physician (PCP), who read some of your posts and thereby says he is working with me, for a referral but with the healthcare system as it is, the best/fastest way to replace a specialist referred by your PCP is to go to that specialist and then request a second opinion. Then, your PCP can replace the first specialist based on a better “second opinion” and/ or more rapport between patient and second specialist over the first, etc. So after 11-12 appointment my PCP  will schedule with a 2nd doctor for a second opinion.


2. Also, I asked my current doctor what do we do if the triple therapy with Incivek does not work, and he said, and I quote: "You come back and we have a couple of options:, He seemed to have some idea on his mind, i.e., not just a general we will wait and see. I know this is a heck of a question, but does anyone know what he may mean?

[Aeschines]

  What do you think  is my chance of success  with a re-treat of triple therapy with Incivek if I wait 18 months, i.e.,  until the virus reverts back to its wild stage, and treat then, as Oceanus says may be an option.

[SYDSDAD1111]

I previously failed 2 other interferon/riba tx's one was a schering trial of double dose peg and riba (2000 mgs!) and I didn't respond,I waited almost 10 yrs for something new and when Incevik came out and with a fresh diagnosis of cirrhosis, I jumped aboard. I cleared the virus in 4 wks and remained clear the whole 48 wks,I now have been 1 1/2 yrs svr,with a normal cbc and cmp, my ast and alt hover around 16/18 haven't seen that in over 20 yrs! it was rough but I made it, so if  you cant wait for the new treatments, my Doc said give it 4 wks and we'll have a good indicator if its going to be worth continuing beyond that.Good luck to you

[ceanothus]

I'm sorry to have to say this, but your doctor really screwed up your treatment. You clearly should have treated for 48 weeks, not 24, and even worse is that he reduced your dosage of Incivek! It is totally against the rules of treatment to reduce that particular drug. The interferon and the ribavirin can both be dose-reduced if necessary, but never the Incivek. The top priority in treating with that drug is to keep the dose as even as possible for the entire 12 weeks, which is why it also has to be taken faithfully every 8 hours (with leeway being no more than 9 hours or less than 7 hours, and why its so important to take it within 20 minutes after eating food with at least 20 grams of fat. All of these are critical to maintaining a pretty even level of the drug in your bloodstream for the entire 12 weeks. The Hepatitis C virus is very good at mutating into a drug-resistant form, and any drop in the level of Incivek in your bloodstream gives it an opening to do that mutating. Once it does mutate, the resistant form quickly multiplies and treatment becomes futile. There was at least one study indicating that once all the drugs are stopped the virus slowly reverts back to its original form and after 18 months it will once again respond to the protease inhibitors, so hopefully that study has been repeated and confirmed and you will be eligible to treat with this class of drugs again in about 18 months. I hope you will find a much better informed doctor to handle your liver care and future treatment. I am so sorry this happened to you, but, sadly, you are not the first person on this forum who had a doctor screw up their treatment. I'm very glad that at least it sounds like your liver is still in pretty good shape, although you can't really be sure without having had a biopsy in the last few years. Please try to find a good hepatologist and see what he recommends for you. This is too important to trust to a doctor who has messed it up once already. Best wishes!

[pooh55811]

Oops, the last link in my previous post was supposed to be this one,  is a link that shows you the results of the various trials with Sofosbuvir, Ledipasvir, and Ribavirin:

http://www.gilead.com/news/press-releases/2013/5/gilead-reports-interim-data-from-phase-2-lonestar-study

[pooh55811]

Before I respond to your most recent questions, let me point out one other thing. I noticed you said you were still Detectable at week 4 and were not Undetectable until week 12. That would have been another reason that you should have done 48 weeks of treatment, not 24 weeks. If one is treating with Incivek and one is still Detectable at week 4, then, according to the recommended protocol, one must treat for 48 weeks. I was in that category. I was still Detectable at week 4 (Interferon, Ribavirin, and Incivek) and I had to treat for 48 weeks. I did attain SVR (cure) after that 48 weeks of treatment.

Now to your most recent question:

If one fails treatment or stops treatment with the triple med treatment of Interferon, Ribavirin, and Incivek, it is not recommended to retreat with the same regimen (Interferon, Ribavirin, and Incivek or Interferon, Ribavirin, and Boceprevir). You have resistant variants now and it takes a while for them to revert back to the wild type HCV virus. If you try to retreat with the same medication, the treatment will most likely fail.

It is possible that you would have attained SVR (cure) if you had treated for the recommended amount of time (48 weeks) for your situation (previous non-responder).  That would have been your best shot at cure with the triple medication regiment. It is also possible that, as a previous non-responder, treatment may not have worked even if you had treated for 48 weeks. Previous non-responders do have a lower rate of cure with the triple med treatment than do those who either never treated before or were previous relapsers or partial responders. You had two reasons why you should have treated for 48 weeks (still Detectable at week 4 and also a previous non-responder). Unfortunately, since you did only 24 weeks of treatment you will never know if you would have attained SVR (cure) had you treated for 48 weeks.

I think if I were you, I would find a knowledgeable and experienced Hepatologist to treat me. A Hepatotlogist should know the correct protocols, should be up to date on new treatments as they become available, and should know about any new trials that may be open to you.  I would also get a liver biopsy and have more testing done to ascertain more about your Genotype and other testing concerning your particular viral strain. I know you said you are Genotype 1a. It would also be good to know your IL28B gene (CC, CT, or TT). For more information on the IL28B gene see the following link:

http://www.treatmentactiongroup.org/hcv/factsheets/il28b

I know it is very discouraging and devastating that you relapsed. However, new drugs are on the way and, hopefully, there will be a new treatment regimen for you sometime late next year or early 2015.

I know it is no consolation, but there are several people on the forum in the same situation as you are in, having relapsed or not succeeded at triple med treatment. They are waiting for the new meds. As soon as new meds become available, there will be many posts concerning them.

There is also a woman who failed triple med treatment a couple of years ago, participated in the ION 2 trial and attained SVR (cure). She did 12 weeks with Sofosbuvir, Ledipasvir, and Ribavirin. You may wish to read her post here:

http://www.medhelp.org/posts/Hepatitis-C/Starting-Sofosbuvir-GS-5885/show/1875802#post_9588922

And here is a link that shows you the results of the various trials with Sofosbuvir, Ledipasvir, and Ribavirin.

http://www.medhelp.org/posts/Hepatitis-C/Starting-Sofosbuvir-GS-5885/show/1875802#post_9588922

Stay on the forum. There will be many more posts in the future about these new drugs and when they will become available.

[Aeschines]

Of course, I meant the treatment I did for 24 weeks, i.e., Incivek, Ribav. & interferon

[Aeschines]

So I would have a poor chance at success if I were to treat again with Incivek for 48 weeks?

[pooh55811]

This link takes you to a site which may be helpful. You can see in the first part of the article there is a chart which shows you the different classes of Direct Acting Antivirals. You can also see that Simeprevir is in the same class as Telaprevir and Boceprevir. That is why there could be some resistance issues if one has already taken Telaprevir or Boceprevir. However, Sofosbuvir and Ledispavir, as well as several other new drugs, are in different classes of Direct Acting Antivirals. There should be no resistance issues with them in terms of having previously taken Telaprevir.

http://www.hepatitis.va.gov/provider/topics/DAA-update.asp

Here are a couple of links to some good articles about the new drugs and you wil be able to do some comparisons:

http://www.natap.org/2013/HCV/050313_02.htm

http://www.natap.org/hcv.htm

http://www.natap.org/2013/EASL/EASL_87.htm