Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials

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• 作者：Gregory J. Dore¹ ; ^&dagger ; ; ^{gdore@kirby.unsw.edu.au" class="auth_mail" title="E-mail the corresponding author} ; Brian Conway² ; ^&dagger ; ; Yan Luo³ ; Ewa Janczewska⁴ ; Brygida Knysz⁵ ; Yan Liu³ ; Adrian Streinu-Cercel⁶ ; Florin Alexandru Caruntu⁷ ; Manuela Curescu⁸ ; Richard Skoien⁹ ; Wayne Ghesquiere¹⁰ ; Włodzimierz Mazur¹¹ ; Alejandro Soza¹² ; Francisco Fuster¹³ ; Susan Greenbloom¹⁴ ; Adriana Motoc¹⁵ ; Victoria Arama⁶ ; David Shaw¹⁶ ; Istvan Tornai¹⁷ ; Joseph Sasadeusz¹⁸ ; Olav Dalgard¹⁹ ; Danielle Sullivan³ ; Xuan Liu³ ; Mudra Kapoor³ ; Andrew Campbell³ ; Thomas Podsadecki³
• 关键词：HCV ; hepatitis C virus ; GT ; genotype ; TPV ; telaprevir ; PegIFN ; pegylated interferon ; RBV ; ribavirin ; SVR ; sustained virologic response ; DAA ; direct-acting antiviral agents ; OBV ; ombitasvir ; PTV ; paritaprevir ; r ; ritonavir ; DSV ; dasabuvir ; IL28B ; interleukin 28B ; RNA ; ribonucleic acid ; MEMS ; Medication Event Monitoring System ; PCR ; polymerase chain reaction ; LLOQ ; lower limit of quantitation ; SF-36v2 ; Short Form&ndash ; 36 version 2 Health Survey ; PRO ; patient-reported outcome ; MCS ; mental componen
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：64
• 期：1
• 页码：19-28
• 全文大小：944 K

文摘

Telaprevir plus pegylated interferon/ribavirin (TPV + PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) and TPV + PegIFN/RBV.

Methods

Treatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r + DSV + weight-based RBV, OBV/PTV/r + DSV (treatment-naïve, GT1b-infected patients only), or 12 weeks of TPV + PegIFN + weight-based RBV and 12–36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR₁₂). Patient-reported outcome questionnaires evaluated mental and physical health during the studies.

Results

Three hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve patients, SVR₁₂ rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r + DSV + RBV and TPV + PegIFN/RBV-treated GT1a-infected patients; SVR₁₂ rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r + DSV + RBV, OBV/PTV/r + DSV, and TPV + PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR₁₂ rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r + DSV + RBV and TPV + PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r + DSV ± RBV than TPV + PegIFN/RBV. Rates of discontinuation due to adverse events (0–1% and 8–11%, respectively, p <0.05) and rates of hemoglobin decline to <10 g/dl (0–4% and 34–47%, respectively, p <0.05) were lower for OBV/PTV/r + DSV ± RBV than TPV + PegIFN/RBV.

Conclusions

Among non-cirrhotic, HCV GT1-infected patients, SVR₁₂ rates were 97–99% with 12 week, multi-targeted OBV/PTV/r + DSV ± RBV regimens and 66–82% with 24–48 total weeks of TPV + PegIFN/RBV. OBV/PTV/r + DSV ± RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events.