Boceprevir in chronic hepatitis C infection: a perspective review.

Boceprevir (Victrelis), from the oral α-ketoamide class of slow-binding reversible hepatitis C virus (HCV)-NS3 protease inhibitors, creates a new class of drugs: direct acting antivirals (DDAs). Boceprevir is highly selective against HCV serine protease. Its use is restricted to genotype 1 HCV infection and it must not be used as monotherapy. Boceprevir is given orally, rapidly absorbed, reaching plasma peak concentration within 1-2 h and is metabolized by aldo-ketoreductase and partly by the cytochrome P450 enzyme CYP3A4/5. Administration with drugs that induce or inhibit CYP3A4/5 could decrease or increase its plasma concentration. The optimal dosage is 800 mg three times daily; capsules should be taken with food. Boceprevir was approved by the US Food and Drug Administration and the European Medicines Agency and is indicated in combination with peginterferon plus ribavirin for the treatment of patients with genotype 1 HCV who have not received previous treatment or whose condition has failed to respond to previous therapy. In the Serine Protease Inhibitor Therapy 2 (SPRINT-2) trial (treatment-naïve patients) and RESPOND-2 trial (patients whose condition relapsed or did not respond to previous treatment), the boceprevir-containing regimen was always more effective than standard of care (SOC). Adverse events were similar in the treatment groups, but in the boceprevir treated group, anemia was more frequent, requiring erythropoietin in nearly 40% of cases. Discontinuation of therapy because of adverse events was identical in all treated groups. As for cost effectiveness, two studies showed that boceprevir plus SOC is cost effective with regard to the lifetime incidence of liver complications, quality of life years, and the incremental cost-effectiveness ratio. The management of this therapy is more complex than before for physicians and patients. The educational role of the physician is crucial for successful therapy and counseling should be carefully given, especially for adherence to the assigned treatment.