AASLD HCV guidelines have updated

[Lynn K]

http://www.hcvguidelines.org/full-report-view

http://www.hcvguidelines.org/full-report/retreatment-persons-whom-prior-therapy-has-failed

Recommended regimen for patients without advanced fibrosis, in whom a previous sofosbuvir-containing regimen has failed.

Based on the limited data available for effective therapy, patients without an urgent need for HCV treatment should defer antiviral therapy pending additional data or consider treatment within clinical trial settings.

Rating: Class IIb, Level C

Recommended regimen for patients who have advanced fibrosis, in whom a previous sofosbuvir-containing regimen has failed.

Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with or without weight-based RBV (1000 mg [75 kg]) for 24 weeks is recommended for patients who have cirrhosis, in whom a previous sofosbuvir-containing regimen has failed.

Emerging data suggest that approximately 10% to 15% of patients with HCV genotype 1 infection treated for 12 weeks with the combination of simeprevir plus sofosbuvir will experience treatment failure, typically owing to viral relapse after discontinuing therapy. Treatment failure appears to be more common in persons infected with HCV genotype 1a and those with cirrhosis.

[dragonslayer]

Thanks for posting this.. One thing that has me concerned is the following quote from these updated guidelines:

" Post hoc analyses of the 2 RBV-free arms assessed baseline predictors of relapse and identified lower relapse rates in patients receiving 8 weeks of ledipasvir/sofosbuvir who had baseline HCV RNA levels below 6 million IU/mL (2%; 2 of 123), and was the same for patients with similar baseline HCV RNA levels who received 12 weeks (2%; 2 of 131). This analysis was not controlled and thus substantially limits the generalizability of this approach to clinical practice.  Shortening treatment to less than 12 weeks should be done with caution and performed at the discretion of the practitioner."

The whole subject of 8 vs 12 wks of treatment is concerning, from the Gilead language, ie '8 wks may be considered' (hardly a ringing endorsement), to the above.   The Gilead published numbers for those with vl < 6mil in the treatment naive group with no cirrhosis in the ion3 trial look definitive and decidedly in favor of the 8 wk treatment for this group.. However the above quote from these guidelines implies that those number are from an uncontrolled analysis.  Does that mean it is completely without value?  For Gilead to publish these relapse number which undoubtedly serve to assist prescribers regarding length of treatment,  and not to indicate in the prescribing brochure and elsewhere that these numbers are from uncontrolled analysis is quite concerning.. 

This appears to substantially muddy  the waters, and Im wondering if I need to go back to my Doctor and plead for an increase from 8 wks to 12 wks of treatment. My biopsies show stage/grade 0-1 and vl is 2.4mil, so Id think if anybody would qualify for 8 wks treatment, it would be people like myself...   

But Im just worried about the language in this portion of the update..  Im on my 25th day of Harvoni treatment.

[BattleTheBeast]

Hi Paul,

If you can get them to give you four more weeks and have it approved I would do it as well. I agree with you that this is really confusing and does muddy the waters. Did Gilead say 8 weeks in order to get more people on the medication and now this new information comes out. I have to say my trust in all of these guidelines is quickly slipping away.

I am going to take it for as long as I can and I am hoping to get the 24 weeks ordered for me. Just need to get the approval end date updated and I will be good to go.  Go for and fight for the extra 4 weeks!

Mel

[dragonslayer]

Thanks, Mel.. I may look into this, but with Gilead's estimates that half of people with genotype 1 of hep C will require just eight weeks of treatment,  if theyre wrong based on uncontrolled analysis of relapse rates not jibing with reality, there's going to be a lot of hell to pay I would think, not just for patients, but for the company itself.

[BattleTheBeast]

Paul,

My doctor told me and showed me the slides when he came back from the conference in Boston that for Harvoni if the VL is under 6 Million with no Cirrhosis it's 12 weeks.

Check out this article Lucinda posted: http://blogs.hepmag.com/lucindakporter/2014/10/harvoni_what_you_nee.html

If this is your first treatment then this is the key sentence for you:
"Patients who have never been treated for HCV, whether they have cirrhosis or not, take Harvoni for 12 weeks. "

You also may want to download and review this:
http://depts.washington.edu/hepstudy/presentations/uploads/103/pptx/ledipasvir_sofosbuvir_master.pptx

Get all your facts, think about what you want to do and have a heart to heart with you doctor. I'd even print this stuff out and bring it with you.

Mel

[dragonslayer]

Mel,

Reviewed the links you posted. Thanks.

re:

>>My doctor told me and showed me the slides when he came back from the conference in Boston that for Harvoni if the VL is under 6 Million with no Cirrhosis it's 12 weeks.<<

Im pretty sure there is an asterisk somewhere in that slide that indicates 8 wks may be considered for the population Im referring to, etc, etc.

re:  >>If this is your first treatment then this is the key sentence for you:
"Patients who have never been treated for HCV, whether they have cirrhosis or not, take Harvoni for 12 weeks. "<<

beneath this bullet point in Lucinda's blog post is this bullet point:

Treatment-naïve patients without cirrhosis whose pre-treatment viral load (HCV RNA) is less than 6 million IU/mL may be considered for 8 weeks of treatment. This is about 40% of eligible patients.

    I agree that its better to be safe than sorry.. But Im not all in on disbelieving Gilead's published svr rates for 8 wks of treatment.   Generally, 8 wks are being prescribed for this group unless there are extenuating circumstances.. I will see if I can get another 4 wks, but I see no reason to push the panic button just yet if the answer is negative.  I'm totally thrilled to have been approved for the 8 wks, and I believe odds are very much in my favor of completing the treatment successfully and achieving SVR.  According to the Gilead numbers, there is absolutely no benefit to going on for another 4 wks.. However, I raised some questions relative to the uncontrolled nature of their analysis.. I would love to get some more information on the reliability of this data.. But short of that, while questioning it somewhat, Im far from condemning it outright.

[BattleTheBeast]

I hear you Paul,

You have to do what you feel is best for you! I am pretty sick so I am pushing for as long as I can get it.  For me to find out I had it out of the clear blue and test for F4 with an 8.3 Million VL kind of shook me up a bit. I knew something was wrong but had no clue it was HepC. Today if I don't get SVR, I am not impressed with my other treatment options. I will do what I have to do but as amazing as I have felt on Harvoni I would rather put that in me for 24 weeks instead of 12. I know there are more options coming soon, the new AbbieV approved today (not loving the multiple meds plus Riba for me)

So lucky me, all these new treatments came out just in time and boom I am on them. I am in a different position and I agree, no need to panic and you have at least a 90% chance of SVR which are pretty damn good odds especially considering what they were before Harvoni. 

I don't know your details or your history so don't let my nervous nelly attitude about HepC treatments get to you, I apologize if I was being pushy! My intention was to just give you the facts I had and let you decide with your doctor.

You will do the right thing for you and that's all that matters

Mel

[Lynn K]

Paul

Straight from the prescribing information

HARVONI for 8 weeks can be considered in treatment-naïve patients without cirrhosis who have pre-treatment HCV RNA less than 6 million IU/mL

I would be nervous but I am in a different situation. The numbers look great for someone in your place good luck!

[dragonslayer]

Thanks all.. The way I see it, Im damned lucky to have been approved at all given my negligible liver damage as portrayed by 2 biopsies.   According to  AALSD guidelines, I shouldnt have been granted treatment at all.  So Im a little loathe to tempt fate here... I keep thinking some insurance exec is going to wake up one morning and read these guidelines, think that I snuck in under the rug, and pull my approval!   I dont really expect that to happen, but feeling like the cat who ate the canary doesnt lend much strength to my desire to push the envelope.   I keep resorting to these Gilead prescribing numbers to keep me sane:

"The treatment difference between the 8-week treatment of HARVONI and 12-week
treatment of HARVONI was –2.3% (97.5% confidence interval –7.2% to 2.5%). Among subjects with a baseline HCV RNA <6 million IU/mL, the SVR was 97% (119/123) with 8-week treatment of HARVONI and 96% (126/131) with 12-week treatment of HARVONI. "

[BattleTheBeast]

I'd say those are great odds in your favor Paul! Go slay that dragon and keep smiling!

Mel

[Lynn K]

Hi Paul

There is on the AASLD site a comment about the way the insurance companies are using the report. The report was neve intended to say the less sick should not be treated just that the F3 F4 patients should get the treatment ASAP.

I think of it as the people with cirrhosis would be first in line but not the only ones in that line. And even with that many of us with cirrhosis still had to fight with our insurance.

Very happy you have Harvoni I won't tell your insurance shhhhh lol

Best of luck to you

Happy holidays

[Mike]

Since the data was obtained from a  "Post hoc analyses", the statement "[T]his analysis was not controlled and thus substantially limits the generalizability.." simply means that the data was gleaned from a study, which was not designed to answer the question.

In other words, participants in the study were not matched or controlled for things like length of infection, gender,  premorbid functioning such as diabetes, high blood pressure, age, & other diseases - all of which could impact outcomes.

Because of this, generalizations from a post hoc analysis of data cannot be made, as the original study was not designed (controlled) to answer that specific question.

However, it appears that Gilead has data to support a 8 week procol for HCV genotype 1 patients who meet specific clinical criterion.

Best wishes, Mike

[dragonslayer]

Hi Paul

There is on the AASLD site a comment about the way the insurance companies are using the report. The report was neve intended to say the less sick should not be treated just that the F3 F4 patients should get the treatment ASAP.

I think of it as the people with cirrhosis would be first in line but not the only ones in that line. And even with that many of us with cirrhosis still had to fight with our insurance.

Very happy you have Harvoni I won't tell your insurance shhhhh lol

Best of luck to you

Happy holidays

Hey Lynn,

If everybody who is infected is supposed to be treated, why does anybody need to be at the front of the line, ie, why is any rationing required?  Is there a shortage of the drug?  providers? insurance money?    If the insurance companies arent supposed to use these guidelines to deny treatment, then where is the resource bottleneck such that there needs to be rationing?

[Mike]

Although this may be uncomfortable to hear, there is a scarcity of medical dollars from third party payers (i.e., insurers and government) and  monies need to be spread across the public health spectrum.

Simply put, Hep-C does not occur in a medical vacuum. There are many, many other diseases and public health issues that need scarce medical dollars. From the diabetes epidemic, to cancer, to heart disease, MS, MD,  to pediatric disorders - the list goes on and on.

The issue becomes more complicated when considering that, 8 out of 10 (80%) of those infected with HCV, do not show signs, symptoms or present with liver damage, and will never have anything more than an chronic HCV infection.

Given this fact, and, considering the cost of current HCV treatment, does everyone really need to be treated now? Or should those in dire need be treated first?

In short, should treatment be rationed?

Ideally, no.

But ideality and reality are not always commensurate - especially when third-party payers are involved.

These are the questions that public health officials, medical ethicist and third-party payers are wrestling with. And, as can be seen, when scarcity of medical dollars - both private and public are factors - the answers become, well,  complicated.

As HCV treatment costs decrease over time, this issue will resolve in a positive manner. But that is not the reality today and priorities to treat appear to the norm for the near future.

Best wishes, Mike

[Lynn K]

Well said Mike

Hi Paul
Well even at the simplest level consider how many specialists are available be how many hours are in a day.

Did you ever see MASH? The most severely injured get treated first but everyone gets treated.

Sadly, the most sick sometimes do not get treated. I saw some additional material about those who have anticipated less than a year to live due to other severe medical conditions along with liver cirrhosis and Hep c. They are the ones who don't get treated at all.

[bridget]

It bothers me that the 8 week treatment plan is being pushed by my insurance company because when I look at the AASLD *Recommended* treatment box and the official Harvoni Prescribing Information  *Recommended* treatment box, http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205834s000lbl.pdf
neither one recommends 8 weeks of Harvoni.  The Prescribing Information box has a footnote under the box saying 8 weeks MAY be CONSIDERED, but 8 weeks is not IN the Recommended treatment box.  The AASLD site warns that "Shortening treatment to less than 12 weeks should be done with caution and performed at the discretion of the practitioner."
My insurer seems to have grasped onto this 8 weeks concept & given it the status of a *Recommended Treatment*

[dragonslayer]

It bothers me that the 8 week treatment plan is being pushed by my insurance company because when I look at the AASLD *Recommended* treatment box and the official Harvoni Prescribing Information  *Recommended* treatment box, http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205834s000lbl.pdf
neither one recommends 8 weeks of Harvoni.  The Prescribing Information box has a footnote under the box saying 8 weeks MAY be CONSIDERED, but 8 weeks is not IN the Recommended treatment box.  The AASLD site warns that "Shortening treatment to less than 12 weeks should be done with caution and performed at the discretion of the practitioner."
My insurer seems to have grasped onto this 8 weeks concept & given it the status of a *Recommended Treatment*

Hi Bridgett... I think the main issue you have is that, as I read elsewhere, your insurance company is considering you as treatment naive, even though you had a failed interferon treament years ago.. I would have thought that would have made you ineligible for the 8wk treatment duration..  If you/your doctor can convince them that Gilead never intended you to be included in the 8wk treatment protocol, the whole discussion of the Ion-3 data would become academic.. Good luck!

[bridget]

Thanks Paul, best of luck to you too!