Page 68 - The Flying Publisher Guide to Hepatitis C Treatment

68 | Hepatitis C Treatment

vs PegIFN/RBV, the most severe being rash, that resolved with
discontinuation of therapy. Serious skin reactions, including
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)
and Stevens-Johnson Syndrome were reported in less than 1% of
subjects who received telaprevir combination treatment
compared to none who received PegIFN/RBV alone. A sequential
discontinuation of drugs was proposed for the management of
moderate or severe rash.
Boceprevir (Victrelis™, Merck) is another potent HCV NS3 PI
with antiviral activity against genotype 1 HCV. Boceprevir is FDA
approved for the treatment of CHC genotype 1 infection, in
combination with PegIFN/RBV, in patients aged 18 years of age
and older with compensated liver disease, including cirrhosis,
who are previously untreated or who have failed previous
interferon and ribavirin therapy. Boceprevir is administered
orally, at a dose of 800 mg three times daily.
The safety and efficacy of triple therapy with oral boceprevir
plus PegIFN/RBV vs PegIFN/RBV alone were demonstrated in a
phase III registration trial for treatment-naive patients, SPRINT-
2 (Poordad 2011) and in previously partial responders and
relapsers to SoC (RESPOND-2) (Bacon 2011). Boceprevir, in
combination with PegIFN/RBV has not been studied in patients
documented to be historical null responders (less than 2 log 10
HCV RNA decline by treatment week 12) during prior therapy
with PegIFN/RBV.
The treatment strategy is different from telaprevir, Boceprevir
being administered in triple combination therapy for 24-44
weeks only after a 4 weeks lead-in phase with PegIFN/RBV alone.
Therefore, RVR was defined as undetectable HCV RNA at week 4
of boceprevir-containing therapy (meaning week 8 of all
therapy, including the lead-in period). In theory, a lead-in phase
may provide the additional advantage of reducing viral
replication and, consequently, the rate of resistance emergence.
However in phase III clinical trials, patients with poor response
to PegIFN/RBV, defined as <1 log 10 decline after 4 weeks lead-in,
had a higher incidence of resistance mutations. Nevertheless, the