Head-to-head studies identify best treatment regimen for hep C

Peginterferon alpha-2a (PegIFNα2a ; commercial name Pegasys) May Yield higher response rate then Peginterferon Alpha-2b (PegIFNα2b : Commercial name Peg Intron.)

Jan 5 2010

In patients with chronic hepatitis C, treatment with peginterferon alpha-2a (PegIFNα2a) plus ribavirin (RBV) better suppresses the virus to undetectable levels in the blood than treatment with peginterferon alpha-2b (PegIFNα2b) plus RBV, according to two new head-to-head studies in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute.

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Additional Reading

Do Differences in Pegylation of Interferon Alfa Matter?, 23 November 2009

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Stefan Zeuzem
pages 34-36
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HCV 2009 / HCV Easy To Follow Slides

New> HCV Genotypes 2 & 3

New> Approach to Patients that Failed to Achieve Sustained Viral Response

New> HCV Genotype 1

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Pegasys plus Copegus

Sustained virological response = (SVR) rates:
• Overall SVR was 63%, which is the highest response rate ever re-ported in a hepatitis C treatment clinical trial.
• Genotype 1 = 52% SVR.
• Genotype 1, high viral load = 47% SVR.
• Genotype 1, low viral load = 65% SVR.
• Genotypes 2 and 3 = 84% SVR.
• Genotypes 2 and 3, high viral load = 82% SVR.
• Genotypes 2 and 3, low viral load = 88% SVR.

FDA-approved Combination Therapy
- Pegasys + Copegus
- (peginterferon alfa-2a + ribavirin)
- PEG-Intron + Rebetol
- (peginterferon alfa-2b + ribavirin
- Intron A + Rebetol
- (standard interferon alfa-2b + ribavirin)
- Roferon A + Ribavirin
- (interferon alfa-2a + ribavirin)

From AASLD 2009 November Liver Meeting

HCV Treatment: The current treatments for hepatitis C, including outcomes, side effects and treatment of various HCV populations

More than 80% of Hepatitis C Patients Treated in Study C208 Achieved an SVR with Telaprevir-Based Regimens - press release from Vertex

83% SVR achieved with twice-daily regimen of telaprevir dosed with PEGASYS and ribavirin

Results highlight the use of response-guided therapy in managing treatment outcomes

Similar safety and tolerability observed between telaprevir-based regimens dosed either twice daily or three times daily

Nov 10

Current Hepatitis C Treatments Work Equally Well

IDEAL Study

Aug 11 09

Pegylated interferon alfa – Pegasys (2a) Verses PegIntron (2b)

The three treatment combinations for clearing the most common form of the hepatitis C virus work equally well with similar side effects, UT Southwestern Medical Center researchers and their colleagues in 13 other institutions have found. Hepatitis C affects nearly 4 million Americans and leads to cirrhosis and liver cancer but can be arrested permanently in many patients.

Results of the two-year study, called the Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy (IDEAL) Trial, are available online and in today's print issue of The New England Journal of Medicine.

Researchers compared a standard dose of the long-acting form of interferon alpha with a lower dose and against a different long-acting interferon alfa preparation. Each achieved about 40 percent clearance of the virus.

"It doesn't seem to make any difference which treatment a physician gives a patient," said Dr. William M. Lee, professor of internal medicine at UT Southwestern and a principal investigator of the study. "These standard treatments were shown to be equally successful when used in combination with the drug ribavirin to treat hepatitis C, so the comparison needed to be done."

Hepatitis C is the most common reason for liver transplantation in the U.S., and there currently is no vaccine to prevent hepatitis C infection.

The IDEAL Trial, conducted between March 2004 and June 2006, included 3,070 patients with the most common and difficult to treat form of hepatitis C virus infection. Participants, who had not received prior treatment, were assigned randomly to groups that received one of the three treatments: a standard dose of peginterferon alfa-2b, a low dose of peginterferon alfa-2b, or peginteferon alfa-2a, each in combination with ribavirin. Sixty-five patients were enrolled at UT Southwestern.

Participants received 48 weeks of treatment and then were followed for six months to see if the virus remained absent from blood samples. A patient is said to have achieved sustained virologic response if six months after treatment the virus remains gone. It is then highly unlikely that the virus will return.

Researchers monitored side effects of the interferon medications throughout the study period. Side effects include extreme flu-like symptoms such as fever, chills, fatigue, depression, muscle aches, chest pain, difficulty breathing, nausea, vomiting, and weight and hair loss.

"There wasn't any difference in side effects either," Dr. Lee said.

Although there was little difference overall in treatment results, researchers did find that women achieved higher rates of virus clearance with the standard dose of peginterferon alfa-2b.

Dr. Lee is currently researching new drug agents such as protease and polymerase inhibitors that, in addition to interferon and ribavirin, could improve rates of virus eradication.

Also involved in the study were researchers from the Duke Clinical Research Institute and Duke University Medical Center; Alamo Medical Research in San Antonio; Kelsey Research Foundation in Houston; the Liver Institute at Methodist Medical Center in Dallas; Liver Specialists of Texas in Houston; Virginia Commonwealth University; Kaiser Permanente San Diego Medical Center in Calif.; University of Miami Center for Liver Diseases; South Florida Center of Gastroenterology; Saint Louis University School of Medicine; Schering-Plough Research Institute in Kenilworth, N.J.; and Johns Hopkins University School of Medicine in Baltimore.

The study was funded by Schering-Plough Corp.

Dr. Lee has received lecture fees from Schering-Plough; research and grant support from Beckman Coulter, Bristol-Myers Squibb, GlaxoSmithKline, GlobeImmune, Schering-Plough and Vertex Pharmaceuticals; and consulting or advisory fees from Gilead, Eli Lilly, Novartis and Westat.

Source: UT Southwestern Medical Center

http://www.medicalnewstoday.com/articles/160178.php

IDEAL Study

July 27 09
The two marketed brands of pegylated interferon alfa – Pegasys (2a) and PegIntron (2b) – are similarly effective for treating chronic hepatitis C, according to the IDEAL Study, reported in the July 22 online edition of the New England Journal of Medicine.

In this trial, sponsored by PegIntron manufacturer Schering-Plough, J.G. McHutchison and colleagues at 118 U.S. sites enrolled 3070 previously untreated patients with HCV genotype 1. Participants were randomly assigned to receive 1.5 (standard dose) or 1.0 (low-dose) mg/kg/week PegIntron plus 800-1400 mg/day weight-adjusted ribavirin, or else 180 mcg/week Pegasys plus 1000-1200 mg/day ribavirin for 48 weeks. Both regimens were administered according to their label direction, which allowed for a larger range of ribavirin doses with PegIntron.

Patients receiving Pegasys had a higher end-of-treatment response rate but were also more likely to relapse, so sustained virological response (SVR) rates 24 weeks after completing treatment were similar: 40.9% with Pegasys, 39.8% with standard-dose PegIntron, and 38.0% with low-dose PegIntron. In all arms, response rates were higher among patients who achieved rapid or early virological response at weeks 4 or 12. The safety profile was similar across all three groups, with about 10% experiencing serious adverse events. The researchers concluded that, "the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b."
http://www.hcvadvocate.org/news/newsRev/2009/HJR-6.7.html#1

Pegasys and PegIntron for Chronic Hepatitis C Perform Similarly in IDEAL Study

Preliminary, Top-line Results from Schering Plough's IDEAL Study: PegIntron versus Pegasys

Head-to-Head Trial Finds HCV Regimens Equal

By Crystal Phend, Staff Writer, MedPage Today
Published: July 22, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Ribavirin in the Treatment of Chronic Hepatitis C

New Drugs In Devolvement From HCV Advocate

If you are on treatment with Pegylated Interferon plus Ribavirin and have have not reached UD at 12 wks you may be wondering what's next?

Do you continue on to 24 wks and see if you clear the virus then. What if you are UD at 24wks and geno 1 / do you stay on treatment longer ?

Click here for more information

Adherence to HCV therapy

Adherence to HCV therapy is one of the most important predictors of successful HCV treatment. While there are well defined and established guidelines for other disease states such as HIV, hypertension and other diseases, it is less clear when it comes to adherence for HCV therapy. There is an established threshold of 80% for HIV, which means that if a patient does not take 80% of their medications, 80% of the time, the chance of a successful treatment outcome is greatly diminished. There have been retrospective (analyzing data from previous trials) studies on hepatitis C treatment adherence that have been able to establish the 80/80/80 rule. This means that someone taking hepatitis C medications is less likely to have a successful treatment outcome if they do not take 80% of interferon and 80% of ribavirin for 80% of the time. However, the 80/80/80 rule is controversial because it has not been studied in well designed prospective clinical trials. Another concern is that the 80/80/80 rule may be sending the wrong message about treatment adherence since it sets a lower threshold for taking medications rather than encouraging people to take 100% of the medications, 100% of the time or as close to 100% as possible – especially during the first twelve weeks of therapy.Currently, pegylated interferon and ribavirin do not become HCV resistant so the question of adherence is only important right now with respect to treatment outcomes. However, questions of adherence will become even more important in the future with the development of anti-viral therapies such as HCV protease and helicase inhibitors that will have the potential to mutate and become HCV resistant. We do know that it is important to take as much of the prescribed medications as possible, but this can be difficult considering the moderate to severe physical and psychological side effects of HCV therapy. There are a number of predictors of treatment response to HCV therapy that are well-recognized as important and this fact sheet will discuss the importance of adherence and well known strategies for helping people achieve a successful treatment outcome. It is also important to remember that not everyone will have a successful treatment outcome even with 100% adherence to HCV therapy.

Continue reading.......... .http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Adherence.pdf

Comparison of the Pegylated Interferons Pegasys and PegIntron for Treatment of Chronic Hepatitis C: Analysis of 16 Randomized Trials - 7/18/08

New HCV Drugs Panel Discussion at EASL 2008

Factors Predicting Response to Therapy for Chronic Hepatitis C -

COLCHICINE VERSUS PEG-INTERFERON ALFA 2B LONG TERM THERAPY: RESULTS OF THE 4 YEAR COPILOT TRIAL

PegIntron vs Pegasys IDEAL Study Findings

The IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess optimal pegylated interferon therapy)

Final Results of the Phase IIIb IDEAL Study (Individualized Dosing Efficacy vs. Flat Dosing to Assess OptimaL PegInterferon Therapy) - May 2008

Preliminary, Top-line Results from Schering Plough's IDEAL Study: PegIntron versus Pegasys -

First Studies Demonstrating Greater than 60% Sustained Viral Response Rates with Half the Standard Treatment Duration in Genotype 1 Chronic Hepatitis C Patients (Vertex press release)

Twice vs Once Weekly Dosing of Peginterferon Alfa 2a in Chronic HCV Genotype 1 Infection: Analysis of Early Viral Kinetics

Oct 07 FDA Safety Changes: Copegus, Intron A