Consensus Interfon plus Ribavirin Produces Sustained Response in Some Prior Non-responders to Pegylated Interferon

By Liz Highleyman

Investigators with the DIRECT study looked at 487 participant who did not achieve SVR with previous treatment using pegylated interferon plus ribavirin, some who initially responded but then relapsed during or after completion of therapy and other who never experienced a substantial decrease in HCV viral load during treatment.

Overall, the study group consisted largely of "hard-to-treat" patients. Almost all had HCV genotype 1, 80% experienced no strong response to earlier treatment, about 70% had high baseline HCV RNA, about 60% had advanced liver disease, and about 20% were African-American.

Participants were assigned to receive consensus interferon (245 patients at 9 mcg/daily and 242 at 15 mcg/daily) or else no further treatment. Consensus interferon is a manufactured product that contains common sequences from multiple other types of interferon.

At 24 weeks, patients who still had detectable HCV RNA were considered non-responders and stopped treatment, while responders continued for 24 more weeks; at the same time, the initial untreated control group was integrated into the treatment arms. Follow-up continued for 24 weeks after the end of treatment, and patients who experienced HCV rebound during this period were considered relapsers.

Results

Overall, about 7% of patients in the 9 mcg consensus interferon group and 11% in the 15 mcg group achieved SVR.

Sustained response rates were higher among participants who were prior relapsers rather than never-responders.

Response was also more likely among participants with lower baseline fibrosis scores.

Previous relapsers who experienced at least a 2 log drop in HCV RNA during their prior course of treatment and who did not have cirrhosis had the highest SVR rate, at 32%.

Adverse events were common, with fatigue, depression, nausea, muscle pain, anemia, and white blood cell deficiencies being reported most often.

Few participants, however, discontinued treatment for this reason.

"The present study demonstrated that some patients with chronic hepatitis C who have failed to respond to treatment with [pegylated interferon] and ribavirin can be successfully retreated with daily [consensus interferon] and ribavirin," the study authors concluded. "The greatest SVR rate during retreatment in the present study was observed in [cirrhosis stage] F0-F3 patients who had a partial virologic response during their prior course of treatment."

7/17/09

Reference
B Bacon, M Shiffman, F Mendes, and others. Retreating Chronic Hepatitis C with Daily Interferon Alfacon-1/Ribavirin after Nonresponse to Pegylated Interferon/Ribavirin: DIRECT Results. Hepatology 49(6): 1836-1846. June 2009.