Short Guide to Hepatitis C_5

Thử nghiệm cho thấy 3 PROOF RẰNG telaprevir dựa trên ba điều trị cũng được cải thiện đáng kể tỷ lệ SVR trong kiểu gen HCV 1 relapsers (69-76%) và không đáp ứng (38-39%) so với retreatment với tiêu chuẩn chăm sóc (14%) (McHutchison 2010).
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Short Guide to Hepatitis C_5 5. New Agents for Treating Hepatitis C | 53 The PROVE 3 trial showed that telaprevir-based triple therapyalso greatly improved SVR rates in HCV genotype 1 relapsers(69-76%) and non-responders (38-39%), compared to retreatmentwith standard of care (14%) (McHutchison 2010). As in the PROVE1 and 2 studies, viral breakthrough was observed morefrequently in patients infected with genotype 1a than in patientsinfected with genotype 1b. Nevertheless, the results of PROVE 3indicate that STAT-C compounds have an enormous potency inprior non-responders and relapsers to standard treatment. Telaprevir and different HCV genotypes. Telaprevir alone orin combination with PEG-IFN and ribavirin was less effective intreatment-naïve patients infected with other genotypes. For HCVgenotype 2 a somewhat weaker antiviral activity in comparisonwith genotype 1 with a mean viral decline of 3.9 log10 IU/ml over14 days monotherapy was observed; in genotype 3 and 4 patientsno significant antiviral activity was detectable (0.5-0.9 log10decline) (Benhamou 2010, Foster 2010). Telaprevir phase III studies. The ADVANCE trial enrolled morethan 1000 treatment-naïve HCV genotype 1 patients to evaluate24 and 48 weeks of telaprevir-based therapy (Jacobson 2010). Tel -aprevir was dosed at 750 mg every 8 hours and given for 8 or 12weeks in combination with PEG-IFN α-2a and ribavirin followedby PEG-IFN α-2a and ribavirin alone until treatment week 24 or48. A response-guided approach was applied to define the overalltreatment period. Patients with or without an extended rapidvirologic response (eRVR, undetectable HCV RNA at treatmentweeks 4 and 12) received 24 or 48 weeks of total therapy,respectively. The novel concept of eRVR was introduced in orderto identify patients with viral breakthrough of telaprevirresistant variants, which may occur after achieving RVRaccording to the traditional definition. SVR rates in theADVANCE trial were 69% and 75% for 8 and 12 weeks triple This is trial versiontherapy followed by 24 or 48 weeks of total treatment (response www.adultpdf.com54 | Hepatitis C Guideguided according to eRVR), compared to 44% after standardtreatment, and eRVR rates were 58% (Figure 5.4a). In the ILLUMINATE trial telaprevir was given for 12 weeks incombination with PEG-IFN α-2a and ribavirin followed by PEG-IFN α-2a and ribavirin alone until treatment week 24 or 48, inde -pendent of whether eRVR was achieved or not (Sherman 2010).Importantly, 48 weeks of total treatment were not superior to 24weeks in patients with eRVR (88 and 92%, respectively). The phase III REALIZE study enrolled more than 650 patientswith prior failure to standard treatment (Figure 5.4a) (VertexPharmaceuticals 2010). PEG-IFN α-2a and ribavirin were givenfor 48 weeks including 12 weeks of telaprevir at a dose of 750 mgevery eight hours. In one treatment arm, telaprevir was initiatedafter a 4 week lead-in phase of PEG-IFN α-2a and ribavirin alone.SVR rates were 86%, 57%, and 31% in relapsers, partialnon-responders, and null-responders to prior treatment,respectively, compared to 24%, 15%, and 5% after standardtreatment, respectively. SVR rates were not improved by thelead-in phase, but the lead-in approach may help to identifypatients with a poor chance of cure even with triple therapy.Viral breakthrough of resistant variants occurred in up to 25% ofall treatment-experienced patients, compared to 1-5% oftreatment-naïve patients. Nevertheless, the REALIZE studyconfirmed the high potential of telaprevir-based triple therapyin treatment-experienced patients. Tolerability of telaprevir. In the PROVE trials, seriousadverse effects led to premature treatment termination in up to18% of all subjects treated with telaprevir in contrast to 4% ofpatients with standard therapy (Hezode 2009, McHutchison2009). The most important side effects of telaprevir are rash,gastrointestinal disorders and anaemia. This is trial version www.adultpdf.com 5. New Agents for Treating Hepatitis C | 55Figure 5.4 – SVR rates in phase III clinical trials evaluating telaprevir(A) or boceprevir (B) in combination with PEG-IFN α and ribavirin.ADVANCE, ILLUMINATE and SPRINT-2 enrolled treatment-naive patients,REALIZE and RESPOND-2 enrolled treatment-experienced patients. Telapre -vir was administered for 8 or 12 weeks in combination with PEG-IFN α-2aand ribavirin, followed by 12-40 weeks of PEG-IFN α-2a and ribavirin alone.Boceprevir was administered over the whole treatment period of 28 or 48weeks in combination with PEG-INF α-2b and ribavirin, except for the first 4weeks of lead-in therapy. eRVR, extended early virologic response; SOC,standard of care; LI, lead-in (4 weeks of PEG-INF α plus ribavirin only). This is trial version www.adultpdf.com56 | Hepatitis ...