LiverHope
Volume 5, Issue 2 February 2003
LiverHope
Volume 5, Issue 2 February 2003
Are you newly diagnosed or do you want more information about Hepatitis
C?
-
Attend
LiverHope too -
-
By
Appointment -
-
February
16, 2003 -
In This Issue
Calendar.............................................................................................. 1
Schering-Plough
Announces Peg-Intron® and
Rebetol®............ 1
Roche
Dramatically Reduces Cost of Combination Therapy for Millions of Americans
Chronically Infected With Hepatitis C 2
Treatment of
Hepatitis C in Liver Transplant Recipients............ 3
Can Ticks
Spread Hepatitis C Virus?.............................................. 4
Man Didn't
Need to Tell Partners He Had Hep C......................... 4
Progression
of Fibrosis in Chronic Hepatitis C............................ 5
Don't Change
the World.................................................................. 5
Schering-Plough Announces Peg-Intron® and Rebetol®
(December 2, 2002) - Schering-Plough Corporation today announced that the U.S. launch of PEG-INTRON® (peginterferon alfa-2b) Powder for Injection and REBETOL® (ribavirin, USP) Capsules combination therapy represents the most successful new product introduction in the company's history, measured in terms of product sales. Since its introduction in October 2001, more than 150,000 hepatitis C patients in the United States have been treated with the combination therapy.
"As a result of the advances we have made in hepatitis C treatment in the last 10 years, we are providing a therapy that was effective in the majority (52 percent) of patients studied. We are extremely pleased with the rapid acceptance by physicians and patients of PEG-INTRON and REBETOL combination therapy," said Richard W. Zahn, president of Schering Laboratories. "We believe this combination therapy has transformed the treatment of hepatitis C, providing established therapeutic value to patients as well as economic value to the U.S. health care system. The proven safety and efficacy of PEG-INTRON, along with its convenient once-weekly dosing, has resulted in more U.S. patients starting
treatment in the past year than during any previous period." An estimated 4 million Americans are infected with the hepatitis C virus (HCV), which contributes to approximately 8,000 to 10,000 deaths each year, according to the Centers for Disease Control (CDC). This toll is expected to triple by the year 2010. The CDC has reported that HCV-associated end-stage liver disease is the most frequent indication for liver transplantation among adults. It is predicted that direct U.S. medical costs to treat HCV-related disease will exceed $13 billion for the years 2010 through 2019, according to a study published in the American Journal of Public Health.
"Along with our extensive clinical development program involving U.S. studies, the real-world treatment experience we've gained with PEG-INTRON and REBETOL in U.S. patients allows physicians to prescribe this combination therapy with confidence," said Robert J. Spiegel, M.D., senior vice president of medical affairs and chief medical officer, Schering-Plough Research Institute. "This deep knowledge base is especially significant given that U.S. patients often have disease characteristics that make them a more difficult group to treat successfully than patients in other countries." American patients with hepatitis C have a higher incidence of genotype 1 virus, which is the most difficult to treat, and typically are older, more cirrhotic and generally have greater body weight, all factors known to negatively affect treatment outcome.
"We designed the clinical study program for PEG-INTRON and REBETOL combination therapy to be consistent with the demographics of the U.S. hepatitis C patient population," Spiegel said. "You can't change a patient's viral genotype, age or degree of cirrhosis, but one factor that a physician can address during treatment is patient body weight, by adjusting dosing accordingly. This gives physicians the flexibility to tailor the appropriate dose of PEG-INTRON to the patient to remove the impact of patient weight on sustained virologic response rates and help achieve consistent treatment outcomes."
PEG-INTRON is approved by the FDA for dosing according to body weight, whether used as monotherapy or in combination therapy with REBETOL, for up to 48 weeks. Data from a large, randomized, controlled clinical study, which served as the basis for U.S. approval of PEG-INTRON and REBETOL combination therapy (Manns et al., Lancet 2001), demonstrated that once weekly administration of weight-based PEG-INTRON (1.5 mcg/kg) in combination with daily REBETOL (800 mg) achieved consistent sustained viral response (SVR) rates across all patient weights. In this study, 68 percent were U.S. patients and, of these, 73 percent
weighed more than 75 kg (165 lbs.). Among U.S. patients weighing more than 75 kg, those treated with weight-based PEG-INTRON and REBETOL achieved a 47 percent SVR versus 39 percent of patients who received standard INTRON® A (interferon alfa-2b, recombinant) Injection three times weekly in combination with daily REBETOL (1,000-1,200 mg). These results were consistent with the overall SVR rates seen in U.S. patients in this study (49 vs. 39 percent, respectively).
PEG-INTRON, the only weight-based alpha interferon product, is approved for use in the United States as monotherapy or in combination therapy with REBETOL for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and are at least 18 years of age.
NUTLEY, N.J. (January 13, 2003) - Roche today announced that Copegus (ribavirin, USP), the medication used in combination with Pegasys (peginterferon alfa-2a) for the treatment of chronic hepatitis C, is being introduced with a list price or wholesale acquisition cost that is 43 percent less per milligram than the other available brand of ribavirin. Copegus will be available in U.S. pharmacies beginning the week of January 13. The list price or wholesale acquisition cost for Copegus is $5.06 per 200mg tablet.
The U.S. Food and Drug Administration (FDA) approved Pegasys and Copegus combination therapy on December 3, 2002, for adults who have compensated liver disease and have not previously been treated with interferon alpha. An estimated 2.7 million Americans are chronically infected with hepatitis C.
"Roche is very proud of the steps the company has taken to drastically reduce the cost of combination therapy for the millions of Americans chronically infected with hepatitis C," said George B. Abercrombie, Roche President and Chief Executive Officer. "With Pegasys and Copegus, physicians and patients can have confidence knowing that this therapy is backed by an unprecedented development program--the most extensive ever conducted in hepatitis C."
Roche has rolled back the list price or wholesale acquisition cost of Copegus to that of branded ribavirin in August 1998. * For patients prescribed 1200mg of ribavirin per day, there is a list price or wholesale acquisition cost savings with Copegus of approximately $7,600 for 48 weeks of therapy.
Pegasys is backed by the most extensive development program ever undertaken in hepatitis C. As part of its clinical development program, Roche conducted five pivotal studies (three for the Pegasys monotherapy indication and two for the Pegasys and Copegus combination therapy indication). Included was a study to evaluate Pegasys monotherapy in patients with cirrhosis and a study to evaluate shorter durations of therapy and lower doses of Copegus for patients with certain genotypes (strains) of the hepatitis C virus.
As a result of the combination therapy study, the following dosing regimens are recommended for Pegasys and Copegus combination therapy:
1.
Genotype 1 and 4: 48-week duration with 180mcg Pegasys weekly
and 1000 - 1200mg of Copegus daily
2.
Genotype 2 and 3: 24-week duration with 180mcg Pegasys weekly
and 800mg Copegus daily.
Pegasys is available as a premixed solution and administered as a subcutaneous injection once a week. Copegus is available as a 200mg tablet, and is administered orally two times a day as a split dose.
* In August 1998, branded ribavirin (Rebetol) was only available in
combination with Intron A, packaged as Rebetron. To extrapolate the August 1998 price of branded ribavirin, the
following calculation was performed on a comparable 1200mg pack: 1998 Rebetron
price ($1,200 for 4 weeks of treatment with 1200mg daily ribavirin and Intron A
3 times per week) minus the 1998 Intron A price ($349.30 for 4 weeks of
treatment with Intron A 3 times per week) = $850.70 for 4 weeks of treatment
with 1200mg per day of branded ribavirin.
Pricing is based on published wholesale acquisition costs by First Data
Bank in August 1998. The current price
of Rebetol was obtained from First Data Bank on January 6, 2003.
Treatment of Hepatitis C in Liver Transplant Recipients
John Lake, MD
January 2003
The increased prevalence of cirrhosis caused by hepatitis C is a major contributor to the explosion in the number of patients being referred for liver transplantation, and therefore for the growing number of patients on the waiting list. By the mid-1990s, hepatitis C was already the most common reason for which liver transplantation was performed1, and currently over 50% of patients referred for liver transplantation in many programs are infected with hepatitis C.
The 5-year survival of transplant patients with hepatitis C is somewhat lower than that of patients with cholestatic liver disease, but better than that of patients with malignant disease. However, due to recurrent infection and disease, which occurs in virtually all liver transplant patients without adequate therapy2, some patients develop aggressive post-transplant disease, which may require re-transplantation or lead to premature death3.
Management of post-transplant hepatitis C includes the identification of patients who may be at risk of more aggressive types of hepatitis C through assessment of clinical variables such as early post-transplant HCV RNA levels, serum ALT levels, and early time to recurrence. Serial liver biopsies may also help identify patients at high risk. Post-transplant patient management may involve changes in the immunosuppressive regimen, in particular in the approach to the diagnosis and treatment of acute cellular rejection, and selection of appropriate immunosuppressive drugs.
A number of anti-viral therapies are currently available or undergoing trials for the treatment or prevention of hepatitis C in liver transplant patients. Standard interferon therapy is well tolerated, improves serum ALT levels, but the likelihood of a sustained viral response is slim. The combination of interferon and ribavirin has shown to be effective – at least transiently - in some patients post-transplant.
Pegylated interferons show improved pharmacokinetics in comparison with standard interferon, allowing once-weekly dosing. Improved anti-viral activity has been reported in the non-transplant setting and in a preliminary study in transplant patients4. In this study, 50% of patients had demonstrated a two-log drop in hepatitis C RNA, and about a third were negative for viral RNA.
In March, I will present some of the latest data regarding the treatment of recurrent hepatitis C in transplant recipients, as well as discuss the effects of immunosuppression on outcomes in hepatitis C infected liver transplant patients.
References
1.
Seaberg
EC et al. Liver transplantation in the United States from 1987-1998: updated
results from the Pitt-UNOS Liver Transplant Registry. Clin Transplants 1998; Chapter 2.
2.
Everhart
JE et al. Recurrent and new hepatitis C virus infection after liver
transplantation. Hepatology 1999;
29:1220–6.
3.
Doyle
HR et al. Assessing risk in liver transplantation. Special reference to the
significance of a positive cytotoxic crossmatch. Ann Surg 1996; 224:168–77.
4.
Riely
C et al. Pegylated (40 kDa) interferon alfa-2a (Pegasys) in post-liver
transplant recipients with established recurrent hepatitis C: a preliminary
report. Am J Transplant 2001;
1(Suppl.):158 (A89).
Can Ticks Spread Hepatitis C Virus?
By
Adam Marcus
Wednesday,
Nov. 20, 2002 (HealthScoutNews)
Everyone knows that ticks spread Lyme disease. But hepatitis C virus?
Scientists at the American Red Cross say they've made a circumstantial case for a tick passing the infection to a Connecticut woman who had no other obvious means of contracting the liver-damaging malady. "Ticks obviously ingest a fair amount of host blood and re-inject blood into the next animal or person they bite. They at least could act like little syringes," says Dr. Ritchard Cable, medical director for the Red Cross's blood services center in Farmington, Conn. He and his colleagues describe the case in a research letter in tomorrow's issue of The New England Journal of Medicine. Cable admits the connection could be coincidence. He has seen no other evidence of ticks ferrying hepatitis C from one person to another, nor to a person from an infected animal -- assuming that animals can contract the virus. What's more, it's not even clear the microbe can survive in ticks.
Still, they have no better explanation for how the woman picked up the disease. She denies being infected on the job or having any high-risk lifestyle habits, such as multiple sex partners or drug use. The woman, a health-care worker and regular blood donor, was participating in a 1999 Red Cross study of a disease called babesiosis that's transmitted by deer ticks. Blood she gave in July 1999 tested positive for that disease, but not for hepatitis C. Yet when the woman gave blood five months later, hepatitis C appeared, a highly unusual event in regular donors. An August blood sample drawn as part of the study also turned up genetic evidence of the virus upon re-examination.
When doctors spoke to the woman, Cable says, she revealed that she'd been ill in September with symptoms that were consistent with hepatitis C, including fatigue, stomach cramps, loss of appetite and dark urine. Intriguingly, she seemed to have acquired the infection during roughly the same window of time that she also picked up babesiosis, he says. Ticks do transmit at least one virus related to hepatitis C, causing tick-borne encephalitis, says Tom Schwan, an expert on the creatures at the National Institutes of Health's Rocky Mountain Laboratories in Hamilton, Mont. In Africa, ticks on rare occasions shuttle a disease called relapsing fever from person to person.
Even so, Schwan says catching hepatitis C from a tick bite would be "an extremely rare event that assumes many things" -- including that the parasites are suitable hosts for the virus. "I would be very cautious" about concluding that the Connecticut case isn't one of mistaken infectivity, he adds. Hepatitis C, which can lead to fatal liver damage, affects nearly 4 million Americans. The disease typically causes no symptoms for years, earning it the nickname the "silent killer."
Most infections occur in drug users sharing tainted needles. Screening of the blood supply has driven the rate of transfusion transmission, once a major problem, to less than one case per million units, according to the U.S. Centers for Disease Control and Prevention.
Man Didn't Need to Tell Partners He Had Hep C
Tue, 29 Oct 2002
FREDERICTON - A judge in New Brunswick (Canada) ruled Tuesday that Darren Jason Jones did not commit a crime when he didn't tell two sex partners that he had hepatitis C. Jones was charged with aggravated assault after he had unprotected sex with two men. Neither of the men has tested positive for the disease.
The Crown said Jones, 24, acted criminally. But Judge Paulette Garnett said Jones did not put his sexual partners at significant risk. Jones burst into tears at her ruling.
Garnett's ruling is considered groundbreaking because it is the first involving hepatitis C and sex. Canadian courts have ruled that people with HIV must tell their sexual partners. The question of whether hepatitis C can be transmitted sexually was key to the ruling. A defense expert testified that the disease couldn’t be transmitted through bodily fluids, only by blood or intravenous drug use. The Crown's medical witness agreed.
But Health Canada's Web site says it can be transmitted through bodily fluids, although drug users sharing syringes is the most common cause of its spread. Health Canada estimates that 240,000 Canadians have hepatitis C. But because they do not show any symptoms, three-quarters of them don't know it. Up to one in five people infected will develop cirrhosis of the liver, a degenerative disease that interferes with the liver's functions.
Written by CBC News Online staff
13 December 2002
Progression of Fibrosis in Chronic Hepatitis C
The best predictors of fibrosis progression in chronic hepatitis C are the extent of serum aminotransferase elevations, degree of hepatocellular necrosis, and inflammation on liver biopsy, find researchers from the United States.
Fibrosis is a hallmark of hepatic cirrhosis. The worsening of fibrosis is probably the best surrogate marker for progression of chronic liver disease. In a study published in the January issue of Gastroenterology, researchers evaluated 123 patients with chronic hepatitis C (CHC).
The research team used liver histology to assess the rate and predictors of progression of fibrosis. Patients in the study had undergone 2 liver biopsies 4 to 212 months apart without intervening treatment. The team graded the liver histology using the histology activity index.
39% of patients showed progression in fibrosis scores. They also staged the fibrosis using a scoring system of 0 (no fibrosis) to 6 (cirrhosis).
The researchers found that of the 123 patients, 39% showed progression in fibrosis scores, 37% showed no change, and 24% showed improvement. Of those with worsening fibrosis, 75% had a 1-point increase and 25% a 2-point or greater increase in scores, and 9% showed progression to cirrhosis.
The team determined that the overall rate of progression was 0.12 fibrosis units per year.
The rate of fibrosis progression was variable. Progression was higher among older patients, those with higher serum alanine and aspartate aminotransferase levels, and those with the most extensive periportal necrosis on initial liver biopsy.
Dr Marc Ghany's team concluded, "The best predictors of fibrosis progression in chronic hepatitis C are the extent of serum aminotransferase elevations and the degree of hepatocellular necrosis and inflammation on liver biopsy". "These findings support the recommendation that patients with normal aminotransferase levels and mild liver histology can safely defer treatment".
Gastroenterology 2003; 124(1): 97-104
07 January 2003
Author
Unknown
Once upon a time, there was a king who ruled a prosperous country. One day, he went for a trip to some distant areas of his country. When he was back in his palace, he complained that his feet were very painful, because it was the first time that he went for such a long trip, and the road that he went through was very rough and stony. He then ordered his people to cover every road of the entire country with leather. Definitely, this would need thousands of cows' skin, and would cost a huge amount of money.
Then one of his wise servants dared himself to tell the king, "Why do you have to spend that unnecessary amount of money? Why don't you just cut a little piece of leather to cover your feet?"
The king was surprised, but he later agreed to his suggestion, to make a "shoe" for himself.
There is actually a valuable lesson of life in this story: to make this world a happy place to live, you better change yourself - your heart, and not the world.
Co-Facilitators
Email: info@liverhope.com
Fax: (763) 566-0589
Website: www.liverhope.com
Helen: (952)
933-0932 – helen@liverhope.com
Pat: (763)
566-3839 – pat@liverhope.com
[1] S. Victoria Ricketts-Wilson
R.Ph., M.P.H., is a Clinical Specialist, Hepatology at Roche Laboratories Inc.
She reviews investigator-initiated research proposals for scientific content,
merit, methodology and safety and supports regional product information
requests. She has a B.S. degree from the School of Pharmacy, Texas Southern
University and an M.P.H from the School of Public Health and Tropical Medicine,
Tulane University. She received a B.A. degree from the University of San
Francisco. Ms. Ricketts-Wilson lives in Maple Grove, MN.