title: Boceprevir.
abstract: Standard treatment for patients with genotype 1 chronic hepatitis C consists of a combination of peginterferon alfa and ribavirin, taken for 24 to 48 weeks. Boceprevir, a drug that inhibits the hepatitis C virus NS3/4A serine protease, is now authorised in the European Union as an adjunct to this standard treatment. In clinical trials, addition of boceprevir did not increase efficacy when the peginterferon alfa-2b + ribavirin combination reduced viral load during the first 4 weeks of treatment. A double-blind, randomised trial including 1097 previously untreated patients showed that adding boceprevir after 4 weeks of peginterferon alfa-2b + ribavirin combination therapy increased the rate of sustained virological response compared with adding placebo after 44 weeks of triple-agent therapy (66.1% versus 37.7%). In early responders, the rates of sustained virological response were similar after 24 weeks and 44 weeks of triple-agent therapy. After failure of standard therapy, a double-blind randomised trial in 403 patients showed that a new 44-week course of treatment induced a significantly higher rate of sustained virological response when boceprevir was added rather than placebo (66% versus 21%). In early responders, the rates of sustained virological response were not reduced by shortening treatment duration to 32 weeks. The main adverse effect of adding boceprevir was an increased incidence of haematological disorders, including anaemia (48% versus 28% with placebo add-on), neutropenia (23% versus 18%), and thrombocytopenia (32% versus 14%). Boceprevir is a potent inhibitor of cytochrome P450 isoenzyme CYP3A4; clinically relevant pharmacokinetic interactions can be thus anticipated when boceprevir is combined with drugs that have a narrow therapeutic margin. Boceprevirtherapy involves taking 4 capsules 3 times daily for 24 to 32 weeks. In practice, adding boceprevir to the peginterferon alfa + ribavirin combination is justified both for first-line treatment and after failure of standard treatment. The impact of the added virological efficacy on morbidity and mortality remains to be determined.
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011392:Proline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011392:Proline; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide