AASLD 2011: Predictors of Response to Boceprevir plus Pegylated Interferon/Ribavirin

Low baseline viral load, hepatitis C virus (HCV) subtype 1b, and absent or mild liver damage predicted sustained response to treatment with boceprevir (Victrelis) plus pegylated interferon/ribavirin, researchers report at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011) this month in San Francisco.

The advent of direct-acting antiviral agents (DAAs) has ushered in a new paradigm in treatment for chronic hepatitis C, but a significant proportion of patients still do not respond to new drugs available to date.

Bruce Bacon from St. Louis Universit yand colleagues performed a follow-up analysis of participants in the pivotal SPRINT-2 (treatment-naive) and RESPOND-2 (treatment-experienced but not prior null responders) trials, looking for predictors of eventual sustained response among patients who exhibited poor early interferon responsiveness.

These studies compared the HCV protease inhibitor boceprevir plus pegylated interferon/ribavirin versus standard therapy using pegyalted interferon/ribavirin alone. Boceprevir triple therapy begins with a 4-week lead-in period of pegylated interferon/ribavirin alone. Response during this lead-in phase is a strong predictor of eventual sustained virological response (SVR) after the end of treatment, but some people with minimal early response nevertheless go on to achieve a cure.

This analysis looked at the 20%-25% of SPRINT-2 participants (n=1097) and the 15%-28% of RESPOND-2 participants (n=403) with poor initial interferon response. In both trials, 28%-34% of such patients achieved SVR with boceprevir triple therapy, compared with only 0%-4% in the standard therapy control groups. Data from the 2 trials were pooled since poor early responders in both were similar.

Results

• Baseline factors significantly associated with sustained response included:
  • HCV subtype 1b vs 1a;
  • Absent or mild liver fibrosis (stage F0-F2) vs advanced fibrosis or cirrhosis (F3-F4);
  • Baseline HCV RNA < 2 million IU/mL vs higher;
• HCV RNA decline after 4 weeks of triple therapy following addition of boceprevir (8 total weeks of treatment) was highly predictive of SVR.
• No patients in either trial who did not experience at least a 3 log decrease in HCV RNA during early treatment went on to achieve SVR.
• Patient sex, age, and race/ethnicity were not independent predictors of SVR, suggesting that the usual differences are less important after accounting for early response.
• Decline in hemoglobin level (an indicator of anemia), steatosis (fatty liver), and baseline ALT were also not significant response predictors.

"HCV subtype and fibrosis level may differentiate between responders and non-responders in poorly interferon-responsive patients," the researchers concluded. "Viral load decline at treatment week 8 is also predictive of response in this population."

Asked whether patients should try treatment now with boceprevir or wait for better DAA drugs, given the suboptimal response rates among poor interferon responders, Bacon answered that this should be an individual decision between patients and practitioners.

"For some, a 30% chance [of a cure] is best thing they’ve heard in years," he said, "but for others it's just not good enough."

Investigator affiliations: St. Louis University School of Medicine, St. Louis, MO; A.O. Fatebenefratelli e Oftalmico, Milan, Italy; University of Miami, Miami, FL; Indiana University School of Medicine, Indianapolis, IN; Vall d'Hebron University Hospital, Barcelona, Spain; Merck Sharp & Dohme Corp., Whitehouse Station, NJ; Northwestern Feinberg School of Medicine, Chicago, IL.

11/29/11

Reference

BR Bacon, S Bruno, ER Schiff, et al. Predictors of Sustained Virologic Response (SVR) among Poor Interferon (IFN) Responders When Boceprevir (BOC) is Added to Peginterferon Alfa-2b/Ribavirin (PR).  62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 33.