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Post Info TOPIC: based on Boston meeting
Isiscat2011


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RE: based on Boston meeting
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Hi Again John:

The study data is conflicting, and as I said, it may be result oriented.  These studies are also based on relatively small patient pools.  You need to read the ION-2 results if you have not done so yet.  

I had a long conversation with my Hepatologist about this very subject: 12 vs 24 weeks of Harvoni (with or without riba).  She was of the opinion that 12 weeks (without riba) might be preferable in my particular situation and she made some excellent points.  In the end I decided that I wanted approval for 24 weeks and she honored my wishes to request that duration.  In the event more information becomes available in the next 3-6 months I can always stop early; but I will have that option.  For the time being, however, 24 weeks without riba is recommended by Gilead, the FDA, and most leading Hepatologists for tx experienced cirrhotics.

Note that each of our situations are somewhat different.  Mine for example:  The factors that favor 12 weeks: I have zero possibility of Sovaldi RAVs because I have never used Sovaldi. I could still have PI RAVs but it has been 3 years since my Incivek tx.  I was a rapid responder to triple therapy (which may or may not factor in to the new DAA tx).  My last Fibroscan score was 13.5 which is right on the cusp of cirrhosis (there is a different scoring system for HCV induced cirrhosis than alcohol induced cirrhosis and 12.5 is considered the cut-off  for HCV induced cirrhosis by most Hepatologists today).  There is ~an 85% chance that 24 weeks will result in overtreatment. 

OTOH, factors that would favor 24 weeks: my last tx created some unintended consequences that have caused my fibrosis to progress more rapidly.  As a tx experienced, cirrhotic, I am running out of time as my odds for HCC and decompensation increase.  I can't afford to potentially acquire New RAVs and then wait for the next treatment to try again.  I can't afford it physically, emotionally, or financially.  That is the position most of us are in.  

We all have to decide whether we will push for a 24 week approval if our docs suggests 12 weeks.  Note that my doctor made this recommendation just after approval; her opinion could have changed by now and updated AASLD guidelines may also impact physicians' choices. This is obviously a cost issue but there will be differences in medical opinions as well.  

The best I can suggest is that you review your own medical factors closely and keep your options open by at least trying to get 24 week approval. Once you close the 24 week door it will be very hard to re-open it.  I know some of what you have been through and want you to have every possible advantage for SVR this time.  

 



__________________

Diagnosed in 2011, Incivek triple in 2011, tx discontinued, Genotype 1a, CT, VL 7mill, cirrhosis dx in 2012, age 67, waiting for new DAAs.
Groupergetter


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Isiscat2011 wrote:

Hi John:

I saw this study too and not sure about its applicability to your situation.  It obviously applies to decompensated cirrhotics.  My take on it is this:  Many insurance companies and public programs are excluding decompensated cirrhotics from Harvoni tx.  Essentially, decomp cirrhotics are not considered a good financial investment, and there are few studies to disprove this.  This study was probably done as a way to persuade payers to approve tx for this population.  Notably, it costs half as much to treat with Harvoni for 12 weeks rather than for 24.

Sometime clinical trials are result oriented.  In other words, they are looking for a specific outcome.  You may have noticed that as Harvoni cost complaints increased recommended tx times for tx naives, who had VLs < 6mill decreased.  Were the clinical trials result oriented?  Did that impact their accuracy? You be the judge.  

We have seen conflicting data for all tx populations. What does it all mean?  Perhaps a way to treat more people for less cost and let the SVR chips fall where they may.  Who knows?  

My feeling is that 12 weeks is going to work for most cirrhotics, compensated or decompensated, but 24 weeks should produce higher real world SVR rates.  Whether it is higher by 2 points or 20 nobody really knows.  These clinical trials are conducted by pharma, and they have value, but the numbers can also be deceiving.  They only publish the results they want published.  

In short, there are no absolutes.  We try to get what we think are the best tx options for our given situations but nobody knows for sure what the results will be.  

I know the 12 vs 24 tx is on your mind but not sure what else to say.  Anybody else?  

 

Isis as usual, your thoughts are on the mark.  Wish there was some means or labs that would give reliable results as to when one has been treated long enough to reach SVR.  Perhaps in time.  Most that have been through this hell understand the reality and necessity of others being treated.  If one could be assured of SVR in 12 by adding Riba it would only make sense.     So many uncertainties.     As larger real world samples become available, protocols may change.   This is still all so new.  Hope we aren't dealing with an "opti-grab" situation here.  The long term affects are still an unknown.   I am reminded of something a friend told me "Therefore do not worry about tomorrow, for tomorrow will worry about itself. Each day has enough trouble of its own."  Thankful for you, and everyone that brings so much good to this forum.

Sandy, give your hubby a hug. Omna, give your little one a hug and a kiss. God's love is great.



__________________

1b  Int/Riba relapse @ 48 weeks.  Stop tx Peg Int/Riba 12 weeks ill. Relapse S/O 6/23/14 :(   Started Harvoni 11/12/14  EOT 4/28/15.  EOT+4 UND :)  SVR! 8/4/15  :)     Thankful for every morning.
JLynch30


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This one sound more like me.
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BOSTON -- Hepatitis C (HCV) patients with cirrhosis are tough to treat. And those who have previously failed therapy are especially difficult.

But 24 weeks of treatment with a newly approved drug combination, sofosbuvir and ledipasvir (Harvoni), cured 97% of patients in a double-blinded, controlled trial, according to Marc Bourliere, MD, of the Saint Joseph hospital in Marseilles, France.

And adding a third drug -- the relatively inexpensive, nonspecific antiviral ribavirin -- allowed investigators to get similar outcomes with just 12 weeks of therapy, Bourliere reported in a late-breaker session at the American Association for the Study of Liver Diseases annual meeting.

The study was the "most compelling" of the six late-breaker presentations, commented Keith Lindor, MD, of Arizona State University in Phoenix, who was not part of the research but who co-moderated the session.

"The biggest issue for many of us treating these patients is the cost," Lindor told MedPage Today.

What the study showed, he said, was that adding ribavirin allowed the researchers to avoid 12 extra weeks of treatment with the more expensive direct-acting combination.

"The cost implications are pretty substantial," he said, especially since the efficacy and safety in a difficult-to-treat group of patients was excellent. The combination is being marketed at $1,125 a pill, for a 12-week cost of $94,500.

Bourliere and colleagues enrolled 155 patients with cirrhosis and randomly assigned them to one of two treatment arms.

In the first, patients were given sofosbuvir and ledipasvir for 24 weeks plus a ribavirin placebo. The other arm began with 12 weeks of a placebo for all three drugs, followed by 12 weeks of the combination plus ribavirin.

The initial placebo period was to allow a safety comparison between sofosbuvir/ledipasvir and no treatment.

The patients were highly treatment-experienced; Bourliere told MedPage Today after his presentation that all of them had failed at least two previous attempts at an HCV cure, using older drugs.

The primary endpoint of the study was unquantifiable HCV RNA in the blood 12 weeks after the end of therapy (SVR12).

One patient in the ribavirin arm dropped out owing to an adverse event during the placebo period, and one patient initially randomized to the ribavirin arm was treated with sofosbuvir/ledipasvir for 24 weeks, leaving 77 patients in each arm.

Outcomes were almost identical, Bourliere reported: 74 of 77 patients in the 12-week ribavirin arm and 75 of 77 patients in the 24-week arm achieved SVR12 96% and 97%, respectively.

Four of the five patients who relapsed had been nonresponders to previous therapy, and the fifth suffered a viral breakthrough while on an earlier regimen.

About one in six patients had baseline viral mutations associated with resistance to NSS5A inhibitors, such as ledipasvir, but that had no effect on the chance of achieving an SVR12, Bourliere and colleagues found.

Adverse events were common -- between 87% and 96% of patients reported at least one -- but most were mild, Bourliere said. Only one serious adverse event, a case of anemia in the ribavirin arm, was attributed to treatment.

The only adverse events that were greater in the placebo arm than in the sofosbuvir/ledipasvir arm were headache and fatigue, the researchers found.



__________________

John   non-responder  

Undetected at week 2 on solvaldi/rib/interferon:  stayed through week 12 but virus came back as soon as I stopped.  on   Harvoni and ribravirin 24 weeks undetected after two. 8/2/15  12 week EOT  UNDETECTED!  SVR

1991-2015 RIP

 
Isiscat2011


Guru

Status: Offline
Posts: 1724
Date:
RE: based on Boston meeting
Permalink  
 

Hi John:

I saw this study too and not sure about its applicability to your situation.  It obviously applies to decompensated cirrhotics.  My take on it is this:  Many insurance companies and public programs are excluding decompensated cirrhotics from Harvoni tx.  Essentially, decomp cirrhotics are not considered a good financial investment, and there are few studies to disprove this.  This study was probably done as a way to persuade payers to approve tx for this population.  Notably, it costs half as much to treat with Harvoni for 12 weeks rather than for 24.

Sometime clinical trials are result oriented.  In other words, they are looking for a specific outcome.  You may have noticed that as Harvoni cost complaints increased recommended tx times for tx naives, who had VLs < 6mill decreased.  Were the clinical trials result oriented?  Did that impact their accuracy? You be the judge.  

We have seen conflicting data for all tx populations. What does it all mean?  Perhaps a way to treat more people for less cost and let the SVR chips fall where they may.  Who knows?  

My feeling is that 12 weeks is going to work for most cirrhotics, compensated or decompensated, but 24 weeks should produce higher real world SVR rates.  Whether it is higher by 2 points or 20 nobody really knows.  These clinical trials are conducted by pharma, and they have value, but the numbers can also be deceiving.  They only publish the results they want published.  

In short, there are no absolutes.  We try to get what we think are the best tx options for our given situations but nobody knows for sure what the results will be.  

I know the 12 vs 24 tx is on your mind but not sure what else to say.  Anybody else?  

 



__________________

Diagnosed in 2011, Incivek triple in 2011, tx discontinued, Genotype 1a, CT, VL 7mill, cirrhosis dx in 2012, age 67, waiting for new DAAs.
JLynch30


Senior Member

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Posts: 292
Date:
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HEPATITIS C TREATMENT

 

Sofosbuvir/ledipasvir with ribavirin is highly effective for people with decompensated cirrhosis

Liz Highleyman
Published: 12 November 2014
Steven_Flamm.jpg
Steven Flamm, speaking at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting. Photo by Liz Highleyman, hivandhepatitis.com.
 

An oral regimen of sofosbuvir/ledipasvir plus ribavirin taken for 12 weeks cured most hepatitis C patients with decompensated cirrhosis, the most advanced stage of liver disease, according to a presentation on Tuesday at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting in Boston.

Over years or decades, chronic hepatitis C virus (HCV) infection can lead to serious complications including cirrhosis and liver cancer. As liver disease progresses, function typically diminishes gradually at first, as the liver can compensate for some damage. Eventually, however, scar tissue blocks normal blood flow and the liver cannot carry out its vital functions such as filtering toxins and producing proteins a condition known as decompensated cirrhosis. People at this stage of liver failure may develop symptoms such as ascites (abdominal fluid build-up), bleeding veins in the oesophagus and stomach, internal infection and hepatic encephalopathy (brain impairment).

Traditionally, before direct-acting antiviral agents became available, hepatitis C patients with decompensated cirrhosis were considered too ill to treat with interferon-based therapy. Those who were treated on an experimental basis did not tolerate drugs well and had a low likelihood of sustained response. There is currently no approved treatment for this population.

With the advent of new direct-acting antivirals that are highly effective and well-tolerated, treating this sickest group of patients has become a priority. Ideally, effective treatment would eradicate HCV and allow the liver to heal, restoring some function and perhaps making liver transplants unnecessary.

Steven Flamm from Northwestern University in Chicago presented findings from SOLAR-1, a study testing an all-oral regimen of direct-acting antivirals that have minimal side-effects and cure most people with less advanced liver disease.

A total of 108 patients with genotype 1 or 4 chronic hepatitis C and decompensated cirrhosis were treated with a once-daily co-formulation of Gilead Sciences' HCV polymerase inhibitor sofosbuvir and NS5A inhibitor ledipasvir (approved and sold as Harvoni in the US). They were randomly assigned to receive therapy for 12 or 24 weeks.

Because people with more advanced liver disease traditionally respond less well to treatment, all patients also took ribavirin, which helps reduce post-treatment relapse. Participants started at a low dose of 600mg/day and the amount was escalated based on tolerability, up to the standard weight-based dose of 1000-1200mg/day. Flamm said that the median dose was just over 600mg/day, with about one-third of patients tolerating the full dose.

Two-thirds of participants were men, more than 90% were white and the median age was about 60 years a bit older than hepatitis C patients with less advanced disease. Approximately two-thirds had harder-to-treat HCV genotype 1a and three people had genotype 4; about 80% had unfavourable IL28B genetic variants. More than 60% had previously undergone unsuccessful hepatitis C treatment.

The patients had decompensated cirrhosis with Child-Pugh-Turcotte (CPT) Class B or C, as determined based on a set of liver function biomarkers and symptoms. About 15% of patients with CPT Class B and 40% of patients with CPT Class C had MELD scores (based on bilirubin, creatinine and blood clotting capacity) of 16-20, about 60% of people in both classes had scores of 10-15 and about 25% of patients with CPT Class B had MELD scores <10. About 60% of patients with CPT Class B and almost all patients with Class C had a history of ascites, and about 60% and 90%, respectively, had hepatic encephalopathy. People with higher MELD scores (indicating more severe disease and low survival probability), very high bilirubin or low platelet counts, serious kidney dysfunction or hepatocellular carcinoma were excluded. This study did not include liver transplant recipients.

Most participants completed treatment. Three people died during the study, three withdrew due to adverse events and four were able to obtain liver transplants.

Overall, 87% of participants treated for 12 weeks and 89% of those treated for 24 weeks achieved SVR12, or continued undetectable HCV viral load 12 weeks after completing therapy, which is considered a cure. Rates were similar for patients with CPT Class B (87% and 89%) and Class C (86% and 90%). Among the few participants with HCV genotype 4, two achieved SVR12 and two were lost to follow-up.

Four people treated for 12 weeks and two people treated for 24 weeks relapsed after the end of therapy, but numbers were too small to draw statistical conclusions about treatment duration. Flamm also noted that the numbers were too small to discern any obvious predictors of relapse.

Successful treatment not only eradicated HCV, but was associated with improvement in liver function. Bilirubin levels fell and albumin blood protein levels rose from baseline to week four post-treatment. Most participants (33) saw decreases or improvement in their CPT scores, with ten having no change and four having higher scores. Likewise, MELD scores also fell for most patients in both the Class B and Class C groups.

Sofosbuvir/ledipasvir plus ribavirin was generally safe and well-tolerated, although almost all participants experienced some adverse events not surprising for such a sick population. About one-quarter experienced serious adverse events, but only four were considered treatment-related. As noted, three people discontinued therapy due to adverse events.

Sofosbuvir/ledipasvir plus ribavirin for 12 weeks "resulted in a high SVR12 rate in HCV patients with genotype 1 and 4 and advanced liver disease," the researchers concluded.

"Relapse rates were similar to relapse rates in patients with compensated cirrhosis," they continued, and "extending treatment duration to 24 weeks did not increase the response rate."

Virological response was associated with improvements in bilirubin, albumin, MELD and CPT scores in patients with Class B and Class C, and Flamm stressed that "sicker patients did equally well."

During the discussion after the presentation, a clinician raised the issue that by lowering patients' CPT and MELD scores which are used to determine transplant priority patients might be put at a disadvantage.

"Some [patients



__________________

John   non-responder  

Undetected at week 2 on solvaldi/rib/interferon:  stayed through week 12 but virus came back as soon as I stopped.  on   Harvoni and ribravirin 24 weeks undetected after two. 8/2/15  12 week EOT  UNDETECTED!  SVR

1991-2015 RIP

 
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