Interferon and Ribavirin Second-Line Option for Hepatitis C

Interferon and Ribavirin Second-Line Option for Hepatitis C
By Crystal Phend, Staff Writer, MedPage Today
Published: June 02, 2009

Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
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SAN FRANCISCO, June 2 -- Some hepatitis C patients who don't respond to standard therapy may get a second chance at eradication with daily interferon alfacon-1 (Infergen) plus ribavirin.
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■Note that the study was not powered to make comparisons between dose groups.
So found Bruce R. Bacon, M.D., of Saint Louis University, and colleagues in the randomized Daily-Dose Consensus Interferon and Ribavirin: Efficacy of Combined Therapy (DIRECT) clinical trial.


Among participants who failed initial treatment with pegylated interferon plus ribavirin, retreatment with the interferon alfacon-1 combination yielded sustained virologic response in 6.9% among the 9-µg dose group and 10.7% in the 15-µg dose group.


The response rates were particularly promising -- up to 31.6% -- in interferon-sensitive patients with low baseline liver fibrosis scores, the researchers reported in the June issue of Hepatology.


This strategy "can be considered for select patients with chronic hepatitis C virus who have failed to respond to prior treatment with pegylated interferon and ribavirin," they wrote.


Roughly half of patients with chronic hepatitis C fail to respond to their first course of the standard combination of pegylated interferon and ribavirin, the researchers noted.


No standard has yet emerged for second-line therapy, since simply repeating the same treatment yields response rates under 10%, they said.


"Some clinicians have used the 'watchful waiting' approach and are anticipating new antiviral therapies with either protease inhibitors or polymerase inhibitors," they wrote.


Others have tried switching pegylated interferon brands, extending the drug's duration, increasing doses, or maintenance dosing, they added.


The DIRECT trial, a registry trial for the combination in second-line therapy, tested high doses of daily consensus interferon in 487 nonresponders.


Interferon alfacon-1 is also known as consensus interferon because it is a recombinant molecule synthesized to contain the most common amino acids from various types of naturally occurring interferon alfa.


Participants were randomized for the first 24 weeks to no treatment or either 9 or 15 µg of subcutaneous interferon alfacon-1 per day, with 1,000 to 1,200 mg of oral ribavirin per day, depending on body weight.


After that period, control group patients were offered randomization to one of the two treatment dose groups.


Pooling the end-of-treatment results for these two phases of the trial, intent-to-treat analysis revealed virologic response in 14.7% of the 9-µg consensus interferon dose group and 18.5% in the 15 µg arm, followed by lower rates of sustained virologic response (defined as undetectable viral levels at least 24 weeks after treatment).


Pooled relapse rates were 52% and 42% among these responders, respectively.


Although the researchers warned that the study was not statistically powered to compare the dose groups, they noted that post hoc analysis revealed no difference in sustained virologic rates between the two (P=0.141).


While control group patients went untreated, none achieved sustained virologic response.


The best sustained virologic response rates were seen in patients with:


•A partial virologic response to their prior course of pegylated interferon treatment, with at least a 2-log10 reduction in hepatitis C viral RNA (11% in the 9-µg group and 23% in the 15-µg group)
•Noncirrhotic patients with fibrosis scores of F0 to F3 at baseline (7.8% and 13.1%, respectively)
•Both interferon sensitivity and low fibrosis scores (10.7% and 31.6%, respectively)

Patients with cirrhosis did not appear to benefit from retreatment with consensus interferon and ribavirin unless they had at least a 1-log drop in viral levels on prior therapy, Dr. Bacon's group noted.


The researchers did not report number needed to treat and could not be contacted in time for publication.


But the consensus interferon-ribavirin combination appeared safe and well-tolerated for second-line therapy, they said.



The study was sponsored by InterMune and Valeant Pharmaceuticals International with additional support for the study publication from Three Rivers Pharmaceuticals.

Dr. Bacon reported conflicts of interest with Three Rivers, Roche, Bristol-Myers Squibb, Schering-Plough, Coley Pharmaceuticals, ISIS, Valeant, and GlaxoSmithKline.


Co-authors reported conflicts of interest for Schering-Plough, Roche, Three Rivers, Idenix, Valeant, Gilead Sciences, Biotex, and Vertex.



Primary source: Hepatology
Source reference:
Bacon BR, et al "Retreating chronic hepatitis c with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results" Hepatology 2009; 49: 1838-46.

Related Article(s):
•AASLD: Consensus Interferon Plus Ribavirin Gives HCV Patients Second Chance

•DDW: Relapsed HCV Patients Achieve Sustained Response with 72-Week Treatment