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August 26, 2008
Hep C Treatment: Comparing the Pegylated Interferons
Learn about the facts on pegylated interferon alfa-2a and pegylated interferon alfa-2b, the standard treatment for chronic Hepatitis C. Comparing and contrasting the pegylated interferons may help better explain a physician’s preference or indifference between the two when treating his or her Hepatitis C patients.
by Nicole Cutler, L.Ac.
Today’s standard treatment for chronic Hepatitis C is a combination of pegylated interferon and ribavirin. While the prescription might seem straightforward, there are actually two different kinds of pegylated interferon – pegylated interferon alfa-2a and pegylated interferon alfa-2b. A general review of their differences and what experts say about their comparison will help those with chronic Hepatitis C better understand the pegylated interferon debate.
What is Pegylated Interferon?
By attaching a protective barrier called polyethylene glycol (PEG) to interferon, pegylated interferon can survive in the body longer than the un-pegylated form, thus reducing dosing frequency. While regular interferon is injected three times a week, pegylated interferon is generally taken once a week. There are two types of pegylated interferons – peg-interferon alfa-2a and alfa-2b. The major difference between the two is how they are dosed:
· 2a – The dose of pegylated interferon alfa-2a (Pegasys) is the same for all patients, regardless of weight or size.
· 2b – The dosing of pegylated interferon alfa-2b (PegIntron) is based on an individual’s weight.
Which Pegylated Interferon is Better?
While there is no other currently approved therapy for chronic Hepatitis C, there is uncertainty among doctors, scientists and patients as to which pegylated interferon is supreme. An overview of the studies evaluating the pegylated interferons has provided conflicting results:
1. In the August 2006 Journal of Hepatology, a small Argentine study compared the pharmacokinetics, pharmacodynamics, and antiviral activity of Pegasys and PegIntron in participants with chronic Hepatitis C genotype 1. The researchers found that patients receiving PegIntron had greater decreases in HCV viral load after eight weeks of therapy, despite lower levels of interferon in the blood of these participants. Interestingly, this trial was sponsored by Schering-Plough, the manufacturer of PegIntron.
2. At the 38th annual Digestive Disease Week in May 2007, Roche announced results of a small study demonstrating that all patients who discontinued treatment with PegIntron and ribavirin due to adverse events within the first 12 weeks were able to complete 12 weeks of treatment with Pegasys and ribavirin. The researchers concluded that Pegasys may be an option for those who are unable to tolerate the side effects of PegIntron.
3. Three studies presented at the 43rd European Association for the Study of Liver Diseases (EASL) held in Milan, Italy in April of 2008 showed that Pegasys had a better cure rate for Hepatitis C than PegIntron. The results of two Italian and one German trial demonstrated that when the dosage of ribavirin was kept at a constant, the cure rate for Hepatitis C was greater in those treated with Pegasys than Pegintron.
4. Also presented at the 43rd EASL were the results of the IDEAL (Individualized Dosing Efficacy vs. flat dosing to assess optimal pegylated interferon therapy) trial sponsored by Schering-Plough. Over 3,000 participants with Hepatitis C genotype 1 were recruited. While relapse after the end of treatment was lower for participants receiving PegIntron, the end of treatment response was higher with participants taking Pegasys. In total, the IDEAL results demonstrated a similar sustained virologic response, safety and tolerability between the two pegylated interferons. This study is being criticized by experts because those receiving Pegasys received a different starting dose of ribavirin than those on PegIntron. In addition, ribavirin dose reduction protocol for side effects was not uniformly administered between these two treatment arms.
5. Published in the August 8, 2006 issue of the Journal of Viral Hepatitis, researchers from Oregon performed an adjusted indirect analysis of trials comparing dual therapy with Pegasys or PegIntron versus dual therapy with non-pegylated interferon. After analyzing 16 trials for sustained virological response and withdrawal due to side effect rates, no statistically significant differences between dual therapy with pegylated interferon alfa-2a and dual therapy with pegylated interferon alfa-2b were found. Despite their apparent similarity, the study authors stated, “Because estimates are imprecise, our results also do not rule out a clinically significant difference. Head-to-head trials are needed to verify the results of indirect analyses and provide additional guidance on optimal treatment choices.”
While logic might lead one to assume that a dosage customized for each individual would deliver safer and more effective results, the data does not completely support this view. The conflicting evidence already in existence clearly indicates that more adequately funded, large, impartial, well-designed studies comparing the two pegylated interferons are needed. Since the differences between Pegasys and PegIntron appear to be negligible, those doing combination therapy for the first time have little reason to be concerned about which pegylated interferon their physician has prescribed.
References:
http://www.bio-medicine.org/medicine-technology/Data-Suggest-that-
Pegasys-May-be-an-Option-in-Hepatitis-C-Patients-0AUnable-to-Tolerate
-Peg-Intron-700-1/, Data Suggest that Pegasys May be an Option in Hepatitis C Patients Unable to Tolerate Peg-Intron, Retrieved August 17, 2008, Bio-Medicine, May 2007.
http://www.hivandhepatitis.com/hep_c/news/2008/071808_a.html, Comparison of the Pegylated Interferons Pegasys and PegIntron for Treatment of Chronic Hepatitis C: Analysis of 16 Randomized Trials, Retrieved August 16, 2008, hivandhepatitis.com, July 2008.
http://www.hivandhepatitis.com/2006roberts/hcv/080906_c.html, Comparison of Pegasys vs Peg-Intron for Treatment of Chronic Hepatitis C, Liz Highleyman, Retrieved August 16, 2008, hivandhepatitis.com, August 2006.
http://www.medicalnewstoday.com/articles/105492.php, Final Results Of Ideal Study Presented At Annual Meeting Of The European Association For The Study Of The Liver (EASL), Retrieved August 16, 2008, MediLexicon International Ltd., April 2008.
http://www.natap.org/2008/HCV/011408_02.htm, IDEAL Study COMMENTARY- Doug Dieterich MD A Healthy Dose of Curiosity Clinical trial results require careful interpretation, Douglas T. Dieterich, MD, Retrieved August 16, 2008, Liver Health Today, January-March 2008.
http://www.ncbi.nlm.nih.gov/pubmed/18482285, Pegylated interferons for chronic hepatitis C virus infection: an indirect analysis of randomized trials, Chou R, et al, Retrieved August 16, 2008, Journal of Viral Hepatitis, August 2008.
http://www.pegasys.com/about-pegasys/what-is-pegasys.aspx, What is Pegasys?, Retrieved August 16, 2008, Hoffman-La Roche Inc., 2008.
http://www.roche.com/inv-update-2008-04-28c, Investor Update, Retrieved August 17, 2008, F. Hoffman-La Roche, April 2008.
http://www.thebody.com/content/art5176.html, HCV Treatment and Monitoring Guide, Retrieved August 16, 2008, The Body, August 2003.
Posted by Editors at 10:52 AM --- Printer-friendly version
August 22, 2008
Advanced Trial Could Change Hepatitis C Treatment
Hundreds of non-responders to interferon-ribavirin combination therapy will be enrolled in a late stage clinical trial for Vertex's telaprevir.
Vertex to begin expanded trial for hepatitis drug
Tuesday, August 19, 2008
Boston Business Journal - by Mark Hollmer
Vertex Pharmaceuticals Inc. will begin a wide-scale late stage human clinical trial for its hepatitis C treatment.
The Cambridge, Mass. company (Nasdaq: VRTX) said on Tuesday that it had agreed with regulatory authorities in the U.S. and European Union to begin the trial for telaprevir in combination with another treatment. Scientists for this trial will focus on patients for whom a previous treatment hasn’t worked.
More than 650 patients will be enrolled at over 100 facilities in the U.S. and the European Union, and enrollment should be complete by the fiscal 2009 first quarter.
Getting a hepatitis C treatment to market would be an enormous achievement. About 6 million patients in the U.S. and European Union alone suffer from hepatitis C, Vertex estimates.
URL for article source:
http://milwaukee.bizjournals.com/boston/stories/2008/08/18/daily10.html
Posted by Editors at 01:51 PM --- Printer-friendly version
August 15, 2008
Silymarin Improves Quality of Life During Hepatitis C Treatment
Although a large-scale study concluded long-term interferon therapy to be ineffectual for Hepatitis C management, it demonstrated improvements in quality of life for participants supplementing with silymarin.
by Nicole Cutler, L.Ac.
Over the past few decades, thousands of clinical studies have been conducted on the effectiveness of different types of complementary and alternative medicine (CAM) in combating chronic liver disease. As the CAM remedy most often advised and used to support liver health, silymarin supplementation has been the focus of a majority of these studies. Even though there is substantial evidence demonstrating silymarin’s benefits to a person with Hepatitis C, trial inconsistencies have prevented it from being totally accepted by the Western medical community. However, a recent result from a very large Hepatitis C clinical trial presents irrefutable evidence of silymarin’s value.
Silymarin
Milk thistle (Silybum marianum) has been used since Greco-Roman times as an herbal remedy for a variety of ailments, particularly liver problems. The active ingredient in milk thistle is known as silymarin. This substance, which actually consists of a group of compounds called flavonolignands, helps repair liver cells damaged by alcohol and other toxic substances. Silymarin also keeps new liver cells from being destroyed by these same substances, reduces hepatic inflammation and has potent antioxidant effects.
Most milk thistle products are standardized preparations extracted from the plant’s seeds. A majority of milk thistle preparations are standardized to contain 70 to 80 percent of silymarin. Since milk thistle products are dietary supplements in the U.S. and therefore not regulated, inconsistencies in concentration, purity and quality are the prime suspects for inconclusive clinical trial results.
CAM Frequency
As the aging population of Americans increasingly strives to take control of their health, their use of CAM rises correspondingly. Surveys show that in 1990, CAM was used by 34 percent of the U.S. population. In 1994, this frequency rose to 42 percent and up to 48 percent in 2004. Estimates show that Americans spend over $27 billion annually on CAM, a total that exceeds the amount spent on conventional medicines.
According to National Institutes of Health researchers, a significant portion of the subjects in the large-scale study evaluating Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) were taking silymarin. Among 1,145 of HALT-C’s participants, the following statistics were noted:
· 56 percent had never taken herbal supplements
· 23 percent were using herbal supplements during the study
· Silymarin constituted 72 percent of the 60 types of herbal supplements used by participants
· Among all participants, 16 percent had used silymarin in the past
· Among all participants, 17 percent used silymarin at the beginning of the study
· Silymarin use correlated strongly with higher education
HALT-C Findings on Silymarin
The large trial investigating the effectiveness of long-term pegylated interferon therapy on Hepatitis C previous non-responders, HALT-C was concluded ineffectual for Hepatitis C management. Even though long-term administration of pegylated interferon did not slow the worsening of liver disease, researchers learned about an advantage of taking silymarin with interferon. With such a large portion of people with chronic Hepatitis C taking silymarin, the researchers looked to see if these individuals demonstrated any differences from their counterparts who were not taking an herbal supplement.
When comparing silymarin users to non-silymarin users in the HALT-C trial, the following was discovered:
1. No beneficial effect of silymarin was found on ALT levels (serum alanine aminotransferases) – an enzyme often elevated with liver injury.
2. No beneficial effect of silymarin was found on Hepatitis C virus RNA levels.
3. Those on silymarin showed significantly fewer liver-related symptoms than non-users.
4. Those on silymarin scored higher on quality-of-life parameters than non-users.
5. After adjusting for age, race, education, alcohol consumption, exercise, body mass index and smoking, silymarin users showed significantly less fatigue, nausea, liver pain, anorexia, muscle and joint pain, and improvements in general health over non-users.
Confirming that silymarin has little direct effect on the Hepatitis C virus, the qualitative values generally used to evaluate virus severity were similar in silymarin users and non-users. However, there were other observable benefits to the silymarin users. By reducing the severity of common Hepatitis C symptoms and interferon side effects, silymarin use demonstrated an obvious advantage to people managing this virus.
Quality of Life
In reducing the liver symptoms of fatigue, nausea, liver pain, anorexia and muscle and joint pain, silymarin improves a person with Hepatitis C’s quality of life. In public health and in medicine, the concept of health-related quality of life refers to a person or group’s perceived physical and mental health. Physicians usually reference quality of life scales to measure the effects of how a chronic illness interferes with daily life.
Although quality of life is not a numerical measurement, many believe it to be the single most important factor in illness recovery.
A Pennsylvania study evaluated the importance of quality of life in patients with a specific type of advanced lung cancer. According to lead author Dr. Nicos Nicolaou, an attending physician in the radiation oncology department at Fox Chase Cancer Center in Philadelphia, “In the past, we've considered the stage of disease or tumor size along with other empirical data to predict how long a patient will survive, but now we know quality of life is a critical factor in determining survival.” Although this study focused on a different type of disease, a growing number of healthcare practitioners believe that enhancing a person’s quality of life improves the outcome of any type of chronic disease.
The most likely reason for CAM’s rising popularity is the increase in quality of life that many receive from its use. Although more research is required to prove that supplementing with silymarin improves the outcome of Hepatitis C infection, the mounting evidence leaves little room for doubt. The quality of life benefits that participants supplementing with milk thistle in the HALT-C trial experienced is enough to motivate most people managing this virus. If supplementing with this popular herb can significantly reduce fatigue, nausea, liver pain, anorexia, muscle and joint pain, and improve general health – it makes sense for people with chronic Hepatitis C to give it a try.
References:
Polyak, Stephen J., Inhibition of T-cell cytokines, hepatocytes NF-kappaB signaling, and HCV infection by standardized silymarin, Gastroenterology, May 2007.
Seeff LB, MD, et al., Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial, Hepatology, January 2008.
Tickerhoff, L., et al., Alternative therapy use in liver transplant recipients, Progress in Transplantation, September 2006.
www.bloodindex.com, Hepatitis C Treatment Reduces the Virus but Serious Liver Problems May Progress, Bloodindex, November 2007.
www.cdc.gov, Health-Related Quality of Life, National Center for Chronic Disease Prevention and Health Promotion, 2008.
www.haltctrial.org, Complementary and Alternative Medicine (CAM) for
the Treatment of Chronic Liver Disease, Leonard B. Seeff, MD, HALT-C News, New England Research Institutes, January 2007.
www.hcvadvocate.org, Health Related Quality of Life and Hepatitis C, David Bernstein, MD, FACP, FACG, Hepatitis C Support Project, 2008.
www.hepatitisneighborhood.com, Quality of Life Important in Hepatitis Management, Physicians Stress, John C. Martin, CuraScript, Inc., 2008.
www.nlm.nih.gov, Quality of Life Predicts Lung Cancer Survival, Robert Preidt, HealthDay, ScoutNews LLC, October 2007.
www.umm.edu, Milk Thistle, University of Maryland Medical Center, 2008.
Posted by Editors at 03:05 PM --- Printer-friendly version
August 12, 2008
Early Hepatitis C Treatment Increases Success
Currently approved treatment for chronic Hepatitis C is about 50 percent effective. New research from Canada claims that early treatment boosts its effectiveness up to 90 percent.
Early Treatment Is Key To Combating Hepatitis C Virus
http://www.sciencedaily.com/releases/2008/08/080808151715.htm
ScienceDaily (Aug. 11, 2008) — Canadian researchers have shown that patients who receive early treatment for Hepatitis C virus (HCV) within the first months following an infection, develop a rapid poly-functional immune response against HCV similar to when infection is erradicted spontaneously, according to a new study.
Therefore, early treatment can restore immune response against HCV and help eliminate the virus rapidly. This new discovery of the mechanisms of viral eradication could contribute to the development of new treatments.
About a quarter of infected individuals eradicate the infection spontaneously, without treatment. Led by Dr. Naglaa Shoukry and Dr. Julie Bruneau, affiliated to both the Research Centre of the Université de Montréal Hospital Centre and the Université de Montréal, as well as with researchers from the Institut national de la santé et de la recherché scientifique (Montréal branch), the study found that early treatment restores a rapid poly-functional immune response, characterized by the simultaneous production of multiple antiviral mediators.
HCV is transmitted through infected blood. Although a quarter of infected patients can eradicate the infection spontaneously, the majority develop persistent infection, a major cause of cirrhosis and cancer of the liver. The only approved treatment for HCV is an anti-viral drug known as pegylated interferon alpha. This drug is successful in only half of cases when administered during chronic infection. Success rates among those treated early after infection are significantly higher or around 90%.
In North America alone, most new HCV infections occur among intravenous drug users (IDUs), a vulnerable population that is often undiagnosed and untreated. In the study, researchers followed a group of IDUs at high risk of HCV infection before and immediately after exposure to HCV. Their findings clearly show the importance of early diagnosis and treatment of HCV – particularly in marginalized populations such as IDUs and aboriginal populations.
The study was funded by Canadian Institutes of Health Research and the Fonds de la recherché en santé du Québec.
Posted by Editors at 10:16 AM --- Printer-friendly version
Popular Blood Thinner May Reduce Liver Scarring for HCV Patients
Successful animal studies have paved the way for a human trial to determine if warfarin prevents liver damage in those with Hepatitis C.
Warfarin may prevent liver failure in hepatitis C patients
http://www.healthcarerepublic.com/news/PHARMACIST/836668/Warfarin-may
-prevent-liver-failure-hepatitis-C-patients/
05-Aug-08
Warfarin could be used to prevent liver failure in thousands of patients with hepatitis C, a new study suggests.
UK researchers found that warfarin significantly reduced the level of liver fibrosis in mice with chronic liver injury.
Digital image analysis of liver histology of wild-type mice treated with warfarin showed a 33 per cent reduction in mean fibrosis area compared with controls, according to the study published in the Journal of Thrombosis and Haemostasis.
The alpha-smooth muscle actin, which is a biochemical marker of fibrosis at a cellular level, was also reduced by 10 per cent in wild-type mice treated with warfarin.
It follows previous research by the same group which found that patients prone to blood clotting who have hepatitis C have accelerated liver scarring.
The researchers have now begun a two-year multi-centre trial, funded by the Medical Research Council (MRC), in 90 hepatitis C patients who have had liver transplants. These patients suffer rapid progression to fibrosis, and the follow-up trial should bring faster results, the researchers say.
Posted by Editors at 10:12 AM --- Printer-friendly version
August 05, 2008
R1626 Could Help Defeat Hepatitis C
Whether added to standard combination therapy or as a monotherapy, studies show that R1626 is a powerful HCV anti-viral medicine.
New treatment therapy helps inhibit hepatitis C
Public release date: 31-Jul-2008
http://www.eurekalert.org/pub_releases/2008-07/w-ntt073108.php
Two new studies examine the use of the nucleoside polymerase inhibitor, R1626, to the standard therapy for hepatitis C. The reports appear in the August issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The articles are available online at Wiley Interscience (www.interscience.wiley.com).
The first study shows that adding the treatment to standard therapy with pegylated interpheron alpha plus ribavirin leads to a synergistic antiviral effect. In the search for new and better treatments, researchers have been testing R1626, which previously has been used to inhibit HCV replication in vitro.
The study group included 104 patients with HCV genotype 1. Twenty-one took 1500 mg of R1626 twice a day along with peginterferon alpha-2a. Thirty-two took 3000 mg of R1626 twice a day along with peginterferon alpha-2a. Thirty-one took 1500 mg of R1626 twice a day along with peginterferon alpha-2a and ribavirin. And 20 took the standard of care treatment of peginterferon alpha-2a with ribavirin.
After four weeks, HCV RNA was undetectable in 29 percent, 69 percent, and 74 percent of patients in the respective study arms, compared to 5 percent of patients receiving the standard of care treatment.
"The results of the present study show a marked increase in antiviral effect in patients when ribavirin is added to the combination of R1626 and peginterferon alfa-2a," the authors report.
In conclusion, the authors report, "this phase 2a study has demonstrated a potent reduction in HCV RNA by R1626 and high viral responses with up to 74 percent rapid viral response after 4 weeks of treatment. The strong antiviral effect between R1626, peginterferon alfa-2a and ribavirin, suggests that the dose of one or both of these agents could be lowered to improve tolerability without significantly compromising efficacy."
A second study shows that, in patients with chronic hepatitis C, the antiviral activity increased with the dosage. Side effects were tolerable and there was no evidence of viral resistance.
For 14 days, the patients were treated with R1626 orally at twice-daily doses of either 500 mg, 1500 mg, 3000 mg, 4500 mg, or placebo. "The decreases in HCV RNA from baseline observed with R1626 indicates potent antiviral activity and lack of viral load rebound in the significant majority of patients following 14 days of monotherapy," the authors report. Current therapy for patients with chronic hepatitis C virus (HCV) requires up to 48 weeks of treatment.
In addition, the study showed that R1626 was well tolerated up to 3000 mg and there was no evidence of viral resistance in this study, perhaps reflecting the potency of R1626 as an anti-viral agent.
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Article: "R1626 plus peginterferon alfa-2a provides potent suppression of HCV RNA and significant antiviral synergy in combination with ribavirin." Pockros, Paul; Nelson, David; Godofsky, Eliot; Rodriguez-Torres, Maribel; Everson, Gregory; Fried, Michael; Ghalib, Reem; Harrison, Stephen; Nyberg, Lisa; Shiffman, Mitchell; Hill, George; Najera, Isabel; Chan, Anna. Hepatology ; August 2008; 10.1002/hep22357.
Article: "Robust antiviral activity of R1626, a novel nucleoside analog: a randomized, placebo-controlled study in patients with chronic hepatitis C." Roberts, Stuart; Cooksley, Graham; Dore, Gregory J.; Robson, Richard; Shaw, David; Berns, Heather; Hill, George; Klump, Klauss; Najera, Isabel; Washington, Carla. Hepatology ; August 2008; 10.1002/hep22321.
For Media Inquiries Only:
Sean Wagner
swagner@wiley.com
781-388-8550
Wiley-Blackwell
Posted by Editors at 11:14 AM --- Printer-friendly version