Three Studies Assess Consensus Interferon for Hepatitis C in Prior Non-responders, Relapsers and Patients with a High Likelihood of Treatment Failure

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Three Studies Assess Consensus Interferon for Hepatitis C in Prior Non-responders, Relapsers and Patients with a High Likelihood of Treatment Failure By Liz Highleyman

Given that a substantial proportion of patients with chronic hepatitis C do not achieve sustained virological clearance following treatment with conventional or pegylated interferon alfa, researchers have explored alternative strategies for treating prior non-responders and relapsers.

At the Digestive Disease Week 2007 conference in May, 3 research teams reported data from studies of consensus interferon in non-responders, relapsers, and patients with a high likelihood of treatment failure.

Study 1

R.H. Ghalib and colleagues assessed SVR rates using 15 mcg daily consensus interferon plus weight-based ribavirin in 49 patients who were non-responders (n = 30; 61%) or relapsers (n = 19; 39%) to prior treatment with pegylated interferon plus ribavirin. Treatment was scheduled for 48 weeks, but was discontinued if HCV RNA remained above 600 IU/mL at week 24.

Among the non-responders, the age range was 35-59 years, 63% were men, 37% were African-American, and 90% had genotype 1 HCV. Among the relapsers, the age range was similar (40-60 years), but fewer (68%) had genotype 1 and only 1 patient (5%) was African-American (a group that responds less well to interferon-based therapy).

Results

• 10% of prior non-responders and 42% of prior relapsers achieved SVR.• Virological response at weeks 4 and 12 was predictive of SVR. • Among the 42 patients with available data on rapid virological response (RVR), 44% with RVR went on to achieve SVR, compared to just 1 patient (5%) without RVR.• SVR occurred in 58% of patients with undetectable HCV RNA at week 12, compared to none with detectable virus. • In both prior non-responders and relapsers, undetectable HCV RNA at week 12 was significantly associated with SVR. • There was no significant difference in SVR rates according to initial fibrosis stage.• Consensus interferon plus ribavirin was well tolerated, with only 7 patients discontinuing treatment due to side effects (20% of non-responders and 5% of relapsers).

The investigators concluded that, "Further investigation of predictive factors of sustained viral response is needed in the non-responder and relapser population to guide selection of appropriate treatment candidates and therapies."

Liver Institute at Methodist Dallas, Dallas, TX; Digestive and Liver Diseases, University of Texas Southwestern Medical School, Dallas, TX; Damascus University, Damascus, Syria.Study 2In the second study, K.O. Salfiti and colleagues evaluated the efficacy of 9-15 mcg daily consensus interferon plus 1-1.2 gm/day daily ribavirin in U.S. veterans who previously failed treatment with conventional or pegylated interferon plus ribavirin. The reported analysis included 38 patients, with a mean age of 52.8 years; 95% were men, 92% were Caucasians, and the remainder were African-American. About two-thirds (73%) had genotype 1 HCV and 67% had liver cirrhosis. By previous treatment status:

• 37% were prior conventional interferon/ribavirin non-responders;• 21% were prior pegylated interferon/ribavirin non-responders;• 8% were non-responders to both prior regimens;• 16% were prior conventional interferon/ribavirin relapsers;• 13% were prior pegylated interferon/ribavirin relapsers;• 5% were relapsers with both prior regimens.

Results

• Among the 33 patients with available treatment outcome data, 5 experienced an end-of-treatment response but SVR data (determined 24 weeks after the completion of therapy) were still pending. • 24 of 38 patients (63%) achieved early virological response (EVR). • 14 of 37 (38%) had undetectable HCV RNA at the end of treatment. • In an intention-to-treat analysis, 5 of 33 patients (15%) achieved SVR.• Among these, 2 had genotype 1, 1 had genotype 2, and 2 had genotype 3.• 7 of 38 patients (18%) stopped treatment due to adverse events, and 10 (26%) required dose reduction.

"Despite high rates of early virologic and end-of-treatment responses, consensus interferon plus ribavirin has a low rate of SVR in patients who had previously failed conventional treatments," the researchers concluded. "Patients who have failed conventional therapy may require longer treatment duration with consensus interferon plus ribavirin or may simply need to wait for more effective treatments."Hepatitis C Resource Center, Veterans Affairs Medical Center, Minneapolis, MN; University of Minnesota, Minneapolis, MN; Division of Gastroenterology & Hepatology, Veterans Affairs Medical Center, San Diego, CA.Study 3

In the third study, M. Swaim and colleagues looked at the use of consensus interferon plus ribavirin in patients who had not been previously treated with combination therapy for hepatitis C, but had attributes associated with a high risk of treatment failure.

The study included 30 consecutive treatment-naive hard-to-treat patients who chose to be treated with daily consensus interferon plus weight-based ribavirin rather than pegylated interferon plus ribavirin.

These patients were deemed to have a high likelihood of treatment failure based on the presence of at least 2 of the following criteria:

• Baseline HCV viral load > 850,000 IU/mL; • Recent biopsy showing advanced fibrosis or cirrhosis (METAVIR stage F3 or F4); • Genotype 1 infection; • African-American race; • HIV coinfection (with optimized antiretroviral therapy).

Results

• 26 of 30 patients (87%) experienced early virological response (EVR) at 12 weeks.• 2 additional subjects did not have 12-week viral load available due to laboratory error, but could be regarded as early virological responders on the basis of undetectable HCV RNA at 24 weeks, giving a total EVR rate of 93%. • 21 patients (70%) had an end-of-treatment response. • 2 subjects (6%) were virological non-responders. • 6 patients (20%) were early virological responders, but experienced virological breakthrough before completing 48 weeks of therapy. • 1 patient with EVR discontinued therapy at 30 weeks due to a neuropsychiatric adverse reaction. • Side effects and hematological toxicities were similar to those observed with pegylated interferon/ribavirin.• SVR data were still pending at the time of the report.

The researchers concluded that, "Daily consensus interferon/weight-based ribavirin is associated with very high EVR and end-of-treatment response [rates]. Consensus interferon/weight-based ribavirin warrants further consideration and evaluation for high likelihood of treatment failure treatment-naive HCV patients.

Noting that 20% of subjects experienced loss of virological suppression during treatment with consensus interferon/ribavirin, they added that, "Virologic breakthrough is an important mode of therapy failure for high likelihood of treatment failure patients, and merits further investigation."

Southeastern Liver Inst., , TN; West Tennessee Health Dept., , TN; Valeant Pharmaceuticals, Costa Mesa, CA.

07/03/07ReferencesRH Ghalib, CD Levine, DA Friedman, and others. Consensus Interferon plus Ribavirin Therapy in Patients who are Nonresponders or Relapsers to Prior PEG IFN plus Ribavirin. Digestive Disease Week 2007 (DDW 2007). Washington, DC. May 19-24, 2007. Abstract M1874.KO Salfiti, B Aqel, SB Ho, and others. Outcome of Daily Consensus Interferon and Ribavirin Treatment For Patients with Chronic Hepatitis C who Failed Previous Treatments: A Single Center Experience. DDW 2007. Abstract M1878.M Swaim, SP Hodges, JF Guidi, and others. Daily Consensus Interferon-? (CIFN) and Weight-based Ribavirin (WBR) as First-Line Therapy for HCV Patients with High Likelihood of Treatment Failure (HLTF): Interim Analysis of a Cohort. DDW 2007. Abstract M1877.

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