Harvoni with or without Rib

[His way]

I will be starting Harvoni in a few weeks. My Doc suggested I do either 12 wks of Harvoni with Ribavirin or 24 wks. of just the Harvoni. We decided on the 24 wks of the Harvoni. I am wondering if adding the dastardly rib on the 24 wk course is advisable. My Doc is willing to add it if I want to. I couldn’t find a 24 wk study w/ that combo. Any insight would be appreciated.
I am GT 1a, stage 4, and have relapsed after treatment 3 times. 2 times with Peg/Rib and once w/ Incivick, peg, and rib. Have been infected over 30 years.
Here we go again.

[pooh55811]

"I am wondering if adding the dastardly rib on the 24 wk course is advisable. I am GT 1a, stage 4, and have relapsed after treatment 3 times. 2 times with Peg/Rib and once w/ Incivick, peg, and rib. "
-------------------------------------------------------

Yes, it is advisable  to add the Ribavirin for 24 weeks, especially since you are Cirrhotic and have failed Tx 3 times. They had better results with the 24 weeks of Harvomi and Riba than with the 24 weeks of Harvoni without Riba. And you should definitely do 24 weeks, not 12 weeks. Again, look at the data in the capsule summary.

This is from Clinical Care Options ..... Capsule summary:

Here are the most recent findings presented at the AASLD.

***** Note this statement towards the bottom of the capsule summary:  Highest SVR12 rate (100%) in treatment-naive and treatment-experienced patients treated with ledipasvir/sofosbuvir and ribavirin for 24 weeks


Ledipasvir/Sofosbuvir Regimens Highly Effective, Safe, and Well Tolerated in Patients With Genotype 1 HCV and Compensated Cirrhosis

Summary of Key Conclusions

    High SVR12 rates with ledipasvir/sofosbuvir with or without ribavirin in pooled analysis of treatment-naive and treatment-experienced patients with genotype 1 HCV infection and compensated cirrhosis who participated in phase II/III clinical trials of ledipasvir/sofosbuvir
        Overall SVR12 rate: 96%
        High SVR12 rates observed in all patient subgroups
        SVR12 rate in treatment-experienced patients lower with ledipasvir/sofosbuvir for 12 weeks vs 12 weeks with addition of ribavirin or with 24-week treatment duration without ribavirin
    Safety outcomes in patients with cirrhosis similar to those previously reported for patients without cirrhosis
        Addition of ribavirin resulted in higher incidence of adverse events (AEs) and hemoglobin declines
        Albumin, ALT, bilirubin, and platelet count all significantly improved from baseline to posttreatment Week 4 with ledipasvir/sofosbuvir therapy

Background

    Interferon-free treatment options needed for HCV-infected patients with cirrhosis
        Cure rates with interferon-based therapy in cirrhotics reduced, tolerability poor
        These difficult-to-treat patients often underrepresented in clinical trials
    Combination therapy with fixed-dose, once daily, single-tablet, all-oral ledipasvir/sofosbuvir 90/400 mg a new treatment option for patients with genotype 1 HCV infection, including patients with cirrhosis
        Sofosbuvir: nucleotide NS5B polymerase inhibitor with potent activity against genotypes 1-6 HCV
        Ledipasvir: NS5A inhibitor with potent activity against genotype 1 HCV
    Ledipasvir/sofosbuvir combination approved by US Food and Drug Administration in October 2014
        Indication for cirrhotics is 12 weeks for treatment-naive and 24 weeks for treatment-experienced patients, both without ribavirin
    Ledipasvir/sofosbuvir, with or without ribavirin, previously demonstrated high efficacy in several clinical trials among patients with genotype 1 HCV infection with or without cirrhosis[2-6]
    Current study analyzed safety and efficacy of ledipasvir/sofosbuvir, with or without ribavirin, among patients with genotype 1 HCV infection and compensated cirrhosis included in clinical trials[1]

Summary of Study Design

    Treatment-naive or treatment-experienced patients with genotype 1 HCV infection and compensated cirrhosis who participated in phase II/III trials of ledipasvir/sofosbuvir pooled for analysis
        Studies included LONESTAR,[2] ELECTRON,[3] ELECTRON-2,[4] 337-0113, ION-1,[5] ION-2,[6] and SIRIUS
    Patients received one of 4 regimens
        Ledipasvir/sofosbuvir for 12 weeks (n = 118)
        Ledipasvir/sofosbuvir + ribavirin for 12 weeks (n = 204)
        Ledipasvir/sofosbuvir for 24 weeks (n = 133)
        Ledipasvir/sofosbuvir + ribavirin for 24 weeks (n = 58)
    Cirrhosis confirmed using 1 of the following
        Liver biopsy
        FibroScan > 12.5 kPa
        FibroTest ≥ 0.75 and AST/platelet ratio index (APRI) > 2 at screening

Baseline Characteristics

    513 patients included in pooled analysis
    Majority of patients were treatment experienced (69%)
    Fewer than 10 patients had international normalized ratio (INR) > 1.5, albumin  2.0 mg/dL at baseline

Main Findings

    Overall, 96% of patients with compensated cirrhosis attained SVR12
        High SVR results regardless of previous treatment experience, treatment duration, and inclusion of ribavirin
        Lowest SVR12 rate (90%) in treatment-experienced patients who received ledipasvir/sofosbuvir without ribavirin for 12 weeks
            12-week regimen with ribavirin had slightly higher SVR rates in this group
        Highest SVR12 rate (100%) in treatment-naive and treatment-experienced patients treated with ledipasvir/sofosbuvir and ribavirin for 24 weeks


There is more in this capsule summary but it is in charts and graphs and won't copy and paste well.


Best of luck. I hope this treatment gets you to SVR.

[can-do-man]

I so agree with pooh. Time is not on our side being cirrhotic, We must throw all the big guns at it we can. There's just not going to be newer treatments for us to keep trying soon.

Myself also being cirrhotic I would insist on 24 weeks with Riba.

Wishing you the best.

[pooh55811]

Here is another thread that was discussing the same type of scenario.

http://www.medhelp.org/posts/Hepatitis-C/Harvoni-Treatment-for-Cirrhotics-Complications/show/2376116

[nan535]

I would like to ask you a couple of questions. Do you have symptoms of decompensation (i.e. portal hypertension, ascites, hepatic encephalopathy, or varices)? What was your most recent hemoglobin result?
     Ribavirin as you have experienced in the past  can be very difficult to handle - more so when combined with interferon. If you have compensated cirrhosis and your hemoglobin is in normal range, I would go with adding the ribavirin to the Harvoni for 24 weeks.  On the other hand, if you do have low hemoglobin and symptoms of decompensation, I would make sure my doctor was prepared to deal with the and adverse effects that may come along if I did decide on adding ribavirin in that scenario.

    I am basing this on my husbands reaction to his last treatment (Sovaldi + Ribavirin for 24 weeks). He is post transplant with symptoms of decompensation and low hemoglobin. It was a very tough treatment for him.
Best wishes and good luck whichever way you go.

Nab

[can-do-man]

I hope your being treated by an Hepatologist.

[sunru]

It is interesting what you have learned about hemoglobin. I noticed my hemoglobin was getting lower than usual before going on treatment. Hemo did not drop at all during tx. I did have some discomfort taking 3 drugs as it felt like a bomb at times. What really helped me get through it was thinking more about God and having tx only last six weeks. In my case, just being compensated and having high ALP and gall bladder issues made it painful to get through at times. It's good that you point out that it can be a delicate fine-line for some patients who are showing early symptoms of decompensate taking when taking additional PIs or Ribavirin.    

[flyinlynn]

Interestingly the results of the ION 2 trial for treatment experienced 20% with cirrhosis the results for 24 weeks with Harvoni +/- riba was 100% for both groups 22/22 with riba and 22/22 without riba

Complete report of ION 1,2,& 3 results

http://depts.washington.edu/hepstudy/presentations/uploads/103/ledipasvir_sofosbuvir_master.pdf

So for that reason and because I have had symptoms of portal hypertension grade 3 varicies, enlarged spleen and a small amount of Ascities I guess that is why my doctor feels the 24 weeks of Harvoni without Ribavirin is what I should be doing just hoping it works this time

[Pamelajean1]

Lynn....I watched this video yesterday and thought of you. Great discussion about to 'rib or not to rib'. Personally, I'd be comfortable with the 24 week no rib.....because of the data you've pointed out.

Title : Advances in Chronic Hepatitis C Management and Treatment

This is a discussion on all the latest treatment regimens by some of the top clinicians in the USA.

Here is the link  http://s318638489.onlinehome.us/files/aasld2014/

[can-do-man]

To flyinlynn. Have you gave any thought to the fact you have already failed Treatment when half the combo was with using Sofosbuvir? These studies you posted only consider those that failed on Interferon and Riba or those two plus a PI. Might be something you and your doctor think about?

[can-do-man]

Lonestar trial conclusion from flyinlynns link.

Interpretation: “These findings suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV, irrespective of treatment history or the presence of compensated cirrhosis. Further clinical trials are needed to establish the best treatment duration and to further assess the contribution of ribavirin.”

[flyinlynn]

There really isn't a lot of data as not a lot of people have failed Sovaldi. There was a small trail with 14 who releapsed on Sovaldi based treatment and all 14 made SVR with 24 weeks of Harvoni alone. Also I really believe the reason I failed was due to length of treatment of 12 weeks.

So being an early treater protocols may change based on real world results but I guess this is what we are going with. Also for my wonderful insurance as Ribavirin is not called for on Harvoni the prescribing information sheet it would be off label and I am not really wanting another fight with express scripts I had a hard enough time getting Harvoni.

When I treated the recommendation was 12 weeks for all. That has since been revised to 24 weeks of Sov/Oly for patients with cirrhosis.

Also as Nan has said Ribavirin can be more of a problem if cirrhosis is more advanced with symptoms of portal hypertension like I have.

I dunno just hoping this works this time

Lynn

[jules2551]

Have to agree with Pooh and Cando. I am going to insist on Harvoni plus Riba for 24 weeks. Whats a couple more pills. Still better than 17 on triple therapy! If he doesnt prescribe it I will find someone who will!

Jules

[sunru]

Pamelajean many thanks for sharing this video on the latest. It is long but very knowledgeable doctors panel. Excellent!  Thank you!

http://s318638489.onlinehome.us/files/aasld2014/

[His way]

Thanks everyone for all the good input, a lot to consider.
Nan535, my latest blood work shows my hemoglobin has returned to my normal 15.2, ALT 47, Platelet 132, HCV count 9,301,253, everything else in range. The terms you used- portal hypertension, ascites, hepatic encephalopathy, or varices. Maybe yes to the ascites, the rest I’m not sure. I will google them. An ultrasound shows enlarged spleen.
Can-do-man, I am being treated by an infectious disease specialist who has been treating HCV exclusively for the 10 years I have known her.
I believe my Docs thinking is that the percentage point or two advantages with the Rib may not be worth the added risk.
Interesting data in the 2 studies flyinlynn and pooh posted.
I will post an update.

[flyinlynn]

I have to agree with His way's remark that the Rib may not be worth the added risk for me as well and as the results were 100% for Harvoni with out Riba I am optimistic for my outcome.

My doctor is the head of the liver department and a liver transplant surgeon she shares offices with Kris Kowdley which I am sure many here will recognize his name. So I have utmost confidence in my team as well.

So I guess I will know how this all works out in late July early August when I get my 12 week results. I think I may ask about having a 4 week post treatmant viral load this time as I have seen many here say that is a good indication of 12 week SVR. If I have failed we will know sooner so mt doctor and I can reassess my situation and get my next move in progress.

Day 2 Harvoni 166 to go

Good luck to all
Lynn

[nan535]

Lynn
As you may recall, my husband had a very difficult time getting through his Sovaldi + Ribavirin treatment for 24 weeks.  I was so relieved it was over yet somehow knew he would relapse despite it all.  Given your symptoms of decompensation (portal hypertension, ascites),  I have to agree with your doctor's decision of putting you on Harvoni alone for 24 weeks.

Honestly, I hope that is what my husband's doctor decides to do too. The thought of going through what he went through last time again is just to hard to think about. He was hospitalized five times and fell 5 times. He had ongoing bouts of hepatic encephalopathy. Once he stopped treatment in late July, he has not been hospitalized since and is stable on his feet. Thankfully, he has had only periodic minimal HE episodes since stopping treatment.  So treatment definitely caused huge problems for him. (Keep in mind that he is post transplant also.)

I think your doctors know you best and are making the best decision for you.
Time will tell if this treatment will cure you of this virus. If you relapse, that does not necessarily mean the result would have been different had you taken the Ribavirin. My husband did and it didn't make a difference.

All the best. Hang in there.

Nan

[jules2551]

Why would you risk the %

[Livelife777]

Have to agree with everyone's position on this one.  Do believe the added Riba for decomp cirrhosis is perhaps to intense.  Nan, I side with you with your husbands hope that forgoing the Riba and extending the time, would be a safer path to follow.
In regards to can-do and Poohs thoughts, I'm taking their view as personally if it were me adding the Riba would want to annihilate those ******** with everything in my arsenal.  
Lets just hope the extension of time for all will do the trick.  It's a tuff call coming from a former Riba treater.  Wish I didn't have to take it, but so glad
I did.
Unfortunately in life there are no guarantees.
.....Kim

[hepcandme]

I wish that I were not going to be taking the Riba.
I have a lot of concerns about my reaction to it and I have cirrhosis, portal hypertension, ascites (a little, I guess, I can't see it anymore), enlarged spleen, no varices or edema but those little spidery vein things on my ankles that show up for 15 minutes and then go away again (what's that about?) - having an ultrasound in a few weeks so I guess we'll see about whether I should be worrying about those things too and I guess time to pay attention to my hemoglobin

I must agree with Lynn about length of treatment though. I think that there is a very good chance that we both would have achieved SVR right about now if we had gone the 24 weeks

It isn't easy, is it?

And I do agree that if there is Any chance of decomp, then no way add the Riba

Nan, you and your husband deserve an easier ride this time so hoping that the Harvoni will do the trick for both you and Lynn

[flyinlynn]

what percentage I see 100 percent with Harvoni 24 weeks without riba?

[His way]

Not to get off topic, but are those taking Harvoni permitted to take Prilosec during treatment? I have terrible acid reflux and really depend on the Prilosec. I was 1st told no antacids including Prilosec, and then I was told it would probably be ok if not taken at the same time as the Harvoni. I think the Riba also causes acid reflex.

[can-do-man]

Prilosec is fine to take as it is a proton pump inhibitor (PPI) And not a antacid... Good luck to you.

[flyinlynn]

Hi
Per the prescription information sheet for Harvoni

http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf

paragraph 7.2 table 3 page 5

Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction

Antacids (e.g., aluminum and magnesium hydroxide)

It is recommended to separate antacid and HARVONI administration by 4 hours.

H2-receptor antagonistsc (e.g., famotidine)
H2-receptor antagonists may be administered simultaneously with or 12 hours apart from HARVONI at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

Proton-pump inhibitorsc (e.g., omeprazole)

Proton-pump inhibitor doses comparable to omeprazole 20 mg or lower can be administered simultaneously with HARVONI under fasted conditions.

These can all cause a decrease in blood concentration of Ledipasvir.

My doctor suggested just to treat heartburn with Tums, Rolaids etc at least 4 hours after taking Harvoni and to avoid Nexium and Prilosec (Omeprazole) if at all possible don't want to risk failure.

I have GERD due to Hiatial hernia so I guess I will justs have to deal with it like before we had omeprazole.

For me it is a small price to pay 6 months of heartburn for freedom from hep c. You could call Support Path for more suggestions.

Good luck
Lynn