Fewer than half of patients given the standard hepatitis C treatment for genotype 1 hepatitis C infection (peginterferon plus ribavirin) for 48 weeks achieve sustained virological response (SVR). But addition of new antiviral treatment boceprevir to the regimen can result in a near-doubling of the response rate, concludes an Article published Online First in The Lancet. The Article is by Dr Paul Y Kwo, Indiana University School of Medicine, Indianapolis, IN, USA, and colleagues.
Chronic hepatitis C virus affects about 170 million people worldwide, and genotype 1 is the most common form of the virus seen in North America and Europe. Cirrhosis induced by hepatitis C virus is the most common indication for liver transplantation and is a major contributor to the worldwide increase in the incidence of liver cancer. Genotype 1 hepatitis C virus infection remains the most difficult to treat with this standard regimen of pegylated interferon and ribavirin. In this two-part study, the authors aim was in part one to establish the safety and efficacy of the NS3 protease (viral enzyme) inhibitor boceprevir when added to peginterferon and ribavirin; and in part two to assess the possibility of using a lower dose of ribavarin.
In part one of this phase 2 trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus were randomly assigned to receive peginterferon alfa-2b 1•5 μg/kg plus ribavirin 800� mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400� mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). The primary endpoint was SVR 24 weeks after treatment.
The researchers found that patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54%] for PRB28; 58/103 [56%] for PR4/PRB24; 69/103 [67%] for PRB48; and 77/103 [75%] for PR4/PRB44; vs 39/104 [38%] for PR48 control. Low-dose ribavirin markedly reduced the effectiveness of the three-drug combination. Boceprevir-based groups had higher rates of anaemia (55% vs 34%) and distortion of their sense of taste (27% vs 9%) than did the control group.
The authors say: "The results of this phase 2 trial have shown that an optimum dose of boceprevir (800 mg three times a day), when added to the standard of care for treatment of chronic genotype 1 hepatitis C virus, significantly increased SVR in both 28-week and 48-week regimens compared with the control of peginterferon alfa-2b and ribavirin."
They conclude: "Boceprevir, in combination with pegylated interferon and ribavirin, achieved high SVR rates with 28 weeks of therapy in most patients and is safe and effective for use up to 48 weeks in the few patients who benefit from longer duration of therapy. We also recorded increased response rates in difficult-to-treat groups, including black participants and those with cirrhosis."
In a linked Comment, Dr Laura Milazzo and Dr Spinello Antinori, University of Milan, Italy, say: "The emergence of drug-resistant virus needs to be addressed...The lesson learned from anti-HIV therapy indicates that complete viral suppression is required to prevent drug resistance. Hence new strategies must be established to explore the combinations of new drugs, improve adherence to treatment, improve pharmacokinetics (for example by boosting the new protease inhibitors with ritonavir to achieve higher plasma concentrations of active drug and to limit the pill burden), and develop resistance testing."
Dr Paul Y Kwo, Indiana University School of Medicine, Indianapolis, IN, USA. T) +1 317 274 3090 E) pkwo@iupui.edu
Dr Laura Milazzo, University of Milan, Italy. T) +39 3398583311 E) laura.milazzo@unimi.it
For full Article and Comment, see: http://press.thelancet.com/hepc.pdf
Journal
The Lancet