Would you want to be treated by primary or general practitioner?

[Shyrlgame]

http://hepatitiscnewdrugs.blogspot.ca/2013/08/expect-miracles-new-drug-for-hepatitis.html?spref=fb


Dr. Gregory Everson

Expect miracles: New drug for hepatitis C may put treatment in the hands of primary care

By: BRUCE JANCIN, Family Practice News Digital Network

ESTES PARK, COLO. – Treatment of hepatitis C infection is likely to shift from gastroenterology and hepatology clinics to primary care physicians’ offices, perhaps as early as next year.

That’s the prediction of Dr. Gregory T. Everson, who cited rapid progress in developing interferon-free treatment regimens as the driving force behind what is anticipated to be a huge change in clinical practice, given that there are an estimated 5 million or more patients with hepatitis C virus (HCV) infection in the United States

Five major pharmaceutical companies are developing oral, interferon-free HCV treatment regimens based upon still-investigational direct-acting antiviral agents (DAAs) that target HCV proteins and their functions. The clinical trials experience to date indicates these DAA-based regimens have substantially higher cure rates, far better tolerability and safety, and a much lower pill burden. Also, they are vastly simpler to administer than are current standard therapies. And all this is being achieved with a 12-week treatment duration instead of the 24 weeks required with standard therapy in 2013, Dr. Everson said at a conference on internal medicine sponsored by the University of Colorado.

"In the past I could say we really had pretty [intolerable] therapy, and it was pretty difficult for patients to take it. Interferon-free therapy is evolving rapidly, and I hope that it will be in primary care physicians’ backyards in the near future. I think this is probably going to be a treatment that you all provide," added Dr. Everson, professor of medicine and director of hepatology at the university.

Indeed, at hepatology clinics around the country, patients with early-stage HCV and their physicians are taking a "wait until next year" attitude toward starting treatment in anticipation that the Food and Drug Administration could approve the first of these new DAAs, sofosbuvir, before the year’s end.

The number of prescriptions for HCV therapy for treatment-naive patients at the University of Colorado clinic has plummeted in 2013 compared with 2012. The only patients starting treatment now are those with advanced HCV liver disease, to halt further disease progression and reduce the risk of developing hepatocellular carcinoma, according to Dr. Everson.

The FDA has granted Gilead Sciences priority review status for sofosbuvir, an oral inhibitor of nucleotide N55b polymerase, with a target decision date in early December. The application for marketing approval is for two indications. One involves sofosbuvir as part of a 12-week, triple-therapy regimen including pegylated interferon and ribavirin in treatment-naive patients with HCV genotypes 1, 4, 5, and 6, based in large part upon the highly favorable results of the phase III NEUTRINO trial (N. Engl. J. Med. 2013;368:1878-87).

The other proposed indication is sofosbuvir in combination with ribavirin as an interferon-free, 12-week regimen in patients with HCV genotypes 2 or 3, based upon the results of the FISSION and POSITRON trials (N. Engl. J. Med. 2013;368:1867-77).

In the NEUTRINO trial, 12 weeks of triple-therapy with sofosbuvir/interferon/ribavirin resulted in a 90% cure rate in patients with HCV genotype 1, which accounts for three-quarters of all HCV infections in the United States. The dropout rate due to side effects was a mere 2%. In contrast, today’s standard therapy, consisting of either of the protease inhibitors telaprevir (Incivek) or boceprevir (Victrelis) combined with pegylated interferon and ribavirin, has a 70%-75% cure rate. And many patients can’t tolerate or are ineligible for interferon.

"When I started treating hepatitis C patients 25 years ago, I was happy because the ALT would normalize in half the patients with genotype 1, but I wasn’t curing anybody. And now triple therapy with sofosbuvir, with a 90% cure rate, could be approved by the end of the year," Dr. Everson marveled.

In the FISSION trial, treatment-naive patients with HCV genotype 2 had a 97% cure rate with 12 weeks of sofosbuvir/ribavirin compared with 78% in those assigned to today’s standard regimen of 24 weeks of pegylated interferon/ribavirin. And sofosbuvir is just one pill per day, coupled with ribavirin at two or three pills twice daily.

In POSITRON, conducted in patients who had relapsed or were nonresponders to the standard 24 weeks of pegylated interferon/ribavirin, 12 weeks of sofosbuvir/ribavirin had an 86% response rate in patients with HCV genotype 2. With an additional 4 weeks of the interferon-free regimen, the cure rate climbed to 94%. Cure rates were lower in genotype 3 patients, but of note, the cure rate in treatment-experienced genotype 3 patients with cirrhosis more than tripled from 19% with 12 weeks of sofosbuvir/ribavirin to 61% with 16 weeks.

Other oral DAAs in the developmental pipeline include simeprevir, daclatasvir, and asunaprevir. The clinical trials experience to date demonstrate that combination therapy with more than one DAA boosts the cure rate even higher than with sofosbuvir/ribavirin. For example, in the phase II, open-label AVIATOR study, 12 weeks of a cocktail comprising three DAAs plus ribavirin brought a 96% cure rate in treatment-naive patients with HCV genotype 1 and a 93% cure rate in those who had previously failed on standard interferon-containing therapy. The AVIATOR cocktail is being formulated as a two-pills-per-day regimen.

Further, Dr. Everson was principal investigator in a Bristol-Myers Squibb–sponsored study of a totally interferon- and ribavirin-free regimen consisting of triple-DAA therapy. Each of the DAAs has a different mechanism of action: Daclatasvir is an inhibitor of the HCV NS5a protein; asunaprevir is an NS3 protease inhibitor; and the agent known for now as BMS-791325 is a nonnucleoside polymerase NS5b inhibitor. The cure rate with 12 weeks of triple-DAA therapy in treatment-naive, noncirrhotic patients with HCV genotype 1 was 94%.

Hepatologists define cure of HCV as an SVR12, or a sustained virologic response featuring no detectable HCV RNA in the blood for 12 weeks after the conclusion of therapy. The likelihood that a patient who achieves an SVR12 will remain HCV free through 10 years is 99%-100% (Gastroenterology 2010;139:1593-1601).

"The future looks pretty good for hepatitis C patients," Dr. Everson observed.

Moreover, curing HCV is going to have major downstream benefits for the health care system, he added. Today, 36% of all patients on the liver transplantation waiting list have HCV; that proportion will drop substantially. There will be fewer cases of hepatocellular carcinoma, B-cell lymphoma, and adult-onset diabetes, a drop in HCV-related autoimmune disorders, and reduced costs of care for patients with chronic HCV.

Dr. Everson reported that he receives research grants from and/or serves as a consultant to or advisory board member for roughly two dozen pharmaceutical companies.

[BoceprevirGal]

  I think all Medical Doctors should be forced to go to a Seminar on the new Hep C meds coming out.
  Like Ski hyas said,all Doctors are different.  My PCPs seem to know nothing about Hep C...how can this be possible?
  

[skiyaltr]

I agree in concept, but all doctors are not equal.  I treated with my PCP.  He treats HIV and Hep C almost exclusively in his practice, and for Hep C is one of the leading docs in Austin.  I was referred to him about 10 years ago from another PCP because of his expertise in the area.  

He treated me as a patient with Hep C and I was happy with him and the results.

I treated in 2006 and failed, then treated in 2012 and now UND.

[pooh55811]

After I moved to MN it took me 9 years just to get someone to test my liver enzymes even though they had been elevated during the 1990s. I kept asking and they kept saying I did not need the test. Then, finally in 2009, I got liver enzymes done and they were elevated. It took another 2.5 years to get anyone to order a Hep antibody panel and that was done only after my liver enzymes had been elevated in Aug. 2009, March 2011, and July 2011.

So no way would I want any of these people handling any of my care if I was diagnosed with Hep C.

[pooh55811]

My PCP (whom I have since fired) told me that I had Hepatitis C, the disease, when my Hep C antibody test came back positive. He did not know the difference between positive Hep C antibody and chronic HCV.

He also does not test Baby Boomers because he does not think it is necessary, even after the CDC recommendations came out. My friend had to be assertive, argue, and insist that she get tested for HCV even though she is a Baby Boomer and she had a blood transfusion decades ago, before the blood supply was screened. He said she did not need the testing, that she probably did not have it. She finally got the test but only after being very assertive and demanding it.

[Revalation]

I was first treated by a dummy who told me to take a Neupogen injection daily until the box of pre-filled was all gone. I was referred to him by  a doctor of internal medicine. If the first few injections hadn't made sick
they could have killed me. Need I say more.

Reva

[hrsepwrguy]

Ha, I would have to say no to that question, I was treated by Dr. Everson (the author) really smart guy and I think he is getting to the point that in the near future, treatment meds are not going to have the same serious side effect profile that they have now and in the future patients will require alot less monitoring while taking the meds

[jules2551]

LOL thats funny but its not.  I am so thankful my GP sent me to Philly.  Living in the boonies is not the place to tx!

[dontworry_behappy1]

Went to my PCP today for a physical.  This is what the PCP said, "Once you have Hepatitis C...you will have it for the rest of your life" and "you can be in remission for awhile".

OK : )

..........and why don't we want PCP 's to treat Hepatitis C?
  

[desrt]

I think, as a general rule, a competent specialist would be the way to go. However, there are exceptions.
My gastro' is arrogant, sometimes poorly informed, and disdainful of patients trying to educate themselves. And he's better than my last gastro' (his former partner who no longer practices in this state). Why do I still go to this clinic? At a 450 mile round trip, it's the closest. Welcome to the world of rural healthcare in West Texas.
Family doc, on the other hand, is willing to discuss my concerns, seems interested in things I've researched, and is willing to try dose adjustments. And bonus, only a 200 mile roundtrip.
In retrospect, tx with family doc would have been less stressful.

[Shyrlgame]

Not!
Have to agree with you guys, can't imagine having any kind of extrahepatic or liver issue and having my GP diagnose it or treat it.  it's so scarey it's laughable.  I can almost understand if there are no issues, no liver damage, but how do you know, until you see a specialist.  Not to mention any complications due to tx.

  But yes Idyllic, one guy's opinion, but gave me a bad feeling in the pit of my gut.

[Idyllic]

Like others I cannot imagine a PCP treating HCV. Keep in mind this is only a prediction by one guy. He really seems to think that sooner or later the all orals will evolve into HCV as being an easy to treat condition that involves only taking the meds (with an eventual subsequent decrease in liver transplants and HCV-related conditions).
Just by the way things look now it seems like he is extremely over optimistic - as far as the pace goes.

That one comment about SVR12 is a bit surprising (Hepatologists define cure of HCV as an SVR12, or a sustained virologic response featuring no detectable HCV RNA in the blood for 12 weeks after the conclusion of therapy.

[BoceprevirGal]

  Hmmmm, well somethingis going to have to be done, when all the Baby-Boomers get tested and decide to treat.  I had a hard time finding a Treatment Doc for a minute there...and I have noticed while reading on here, that the amount of Hepatologists seems meager.

[ppmguy]

            no i would not.  it would be a mess.  i dont see things changing much.  my feeling is, "the dr or NP that treats hep c exclusively would be the best bet.  

[orphanedhawk]

I would not however, for someone with no liver damage whatsoever, it might not be problematic.

[jules2551]

I third the motion!  "absolutely not"....too many factors involved.  

[dontworry_behappy1]

I second pooh's answer.  "absolutely not" for exactly the same reasons.

[pooh55811]

"Would you want to be treated by primary or general practitioner?"
------------------------------------------------

My unequivocal answer would be, "absolutely not."

A pretty large number of the Gastroenterologists cannot get Hepatitis C treatment right so I don't think PCPs and GPs will get it right either.

I think that some doctors think that they can just copy a treatment algorithm from someplace and follow it and that is all they have to do. That sounds good but it often does not work in reality. We are not all carbon copies of each other. First of all, they have to have the correct treatment algorithm (which, as we know, many doctors don't seem to have). Second, they have to follow it, which some doctors do not do. Third, they have to know what to do if something arises that requires some independent thought and problem solving and action, like a side effect or a treatment complication, and many doctors seem to have no clue about side effects or treatment complications. Given that most of the current doctors treating Hep C are GIs, and we are seeing problems with the way they treat (or fail to treat) Hep C, I certainly would not trust a PCP or a GI to treat my Hep C (if I still had it). That is just plain scarey.