Laurie Barclay, MD
March 31, 2011 — Boceprevir is effective in the treatment of previously treated and untreated patients with hepatitis C virus (HCV) infection, according to the results of 2 randomized trials reported in the March 30 issue of the New England Journal of Medicine.
RESPOND-2 Trial
"In patients with chronic infection with [HCV] genotype 1 who do not have a sustained response to therapy with peginterferon–ribavirin, outcomes after retreatment are suboptimal," write Bruce R. Bacon, MD, from Saint Louis University School of Medicine in Missouri, and colleagues from the HCV Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) investigators. "Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3...active site, has been suggested as an additional treatment."
The study goal was to examine the effect of boceprevir added to peginterferon–ribavirin for retreatment of patients with chronic HCV genotype 1 infection. During the lead-in period, the 403 participants all received peginterferon alfa-2b and ribavirin for 4 weeks. Using a 1:2:2 ratio, participants were randomly assigned to group 1 (control group) receiving placebo plus peginterferon–ribavirin for 44 weeks, group 2, or group 3. Participants in group 2 received boceprevir plus peginterferon–ribavirin for 32 weeks, and patients in whom the HCV RNA level was detectable at week 8 received placebo plus peginterferon–ribavirin for 12 more weeks. In group 3, participants received boceprevir plus peginterferon–ribavirin for 44 weeks.
Compared with the control group, the 2 boceprevir groups had a significantly higher rate of sustained virologic response (group 2, 59%; group 3, 66%; control group, 21%; P < .001). Among participants with an undetectable HCV RNA level at week 8, sustained virologic response rate was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients in whom HCV RNA level decreased by less than 1 log10 IU/mL at treatment week 4, rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively.
The boceprevir groups had higher frequencies of anemia than the control group, resulting in administration of erythropoietin in 41% to 46% of boceprevir-treated patients compared with 21% of the control patients.
"The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon–ribavirin alone," the study authors write.
SPRINT-2 Trial
The second study, a double-blind trial by Fred Poordad, MD, from Cedars-Sinai Medical Center in Los Angeles, California, and colleagues from the Serine Protease Inhibitor Therapy 2 (SPRINT-2) investigators, had a study design similar to that of the RESPOND-2 study except that participants were previously untreated adults with HCV genotype 1 infection. Nonblack patients (n = 938) and black patients (n = 159) were enrolled and analyzed separately.
Sustained virologic response in the nonblack cohort occurred in 40% (125/311) of the patients in group 1, 67% (211/316) of the patients in group 2 (P < .001), and 68% (213/311) of the patients in group 3 (P < .001). For the black cohort, the corresponding rates were 23% (12/52 patients), 42% (22/52 patients; P = .04), and 53% (29/55 patients; P = .004), respectively.
Forty-four percent of patients in group 2 received peginterferon–ribavirin for 28 weeks. Dose reductions caused by anemia occurred in 13% of control patients and 21% of patients receiving boceprevir, and discontinuations caused by anemia in occurred in 1% and 2% of control patients and patients receiving boceprevir, respectively.
"The addition of boceprevir to standard therapy with peginterferon–ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection," the study authors write. "The rates were similar with 24 weeks and 44 weeks of boceprevir."
Limitations of this study include relatively small numbers of patients with cirrhosis and relatively small numbers of black patients in whom the HCV RNA level was detectable between weeks 8 and 24, warranting further study to define optimal therapy in these populations.
New Era of HCV Therapy
In an accompanying editorial, Donald M. Jensen, MD, from the Center for Liver Diseases, University of Chicago Medical Center in Illinois, discusses the beginning of a new era of HCV therapy. He noted that adverse effects associated with boceprevir treatment included anemia, rash, dry skin, and dysgeusia. However, only 8% to 12% of patients discontinued boceprevir because of these adverse events.
"HCV protease inhibitors represent a major advance in our ability to treat chronic HCV infection," Dr. Jensen writes. "Future therapy will be more complex, not easier, but the improvement in the rate of sustained virologic response with boceprevir, to nearly 70% in the SPRINT-2 trial and to more than twice the rate in previously treated patients in HCV RESPOND-2, have been eagerly awaited. We will soon embark on a new era of successful HCV therapy."
Schering-Plough (now Merck) supported both studies. Disclosure forms provided by the study authors and editorialists are available with the full text of these articles at NEJM.org.
N Engl J Med. 2011;364:1207-1217, 1195-1206, 1272-1274.
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
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