Bruno S, Bollani S, Zignego A L, Pascasio J M, Magni C, Ciancio A, Caremani M, Mangia A, Marenco S, Piovesan S, Chemello L, Babudieri S, Moretti A, Gea F, Colletta C, Perez-Alvarez R, Forns X, Larrubia J R, Arenas J, Crespo J, Calvaruso V, Ceccherini Silberstein F, Maisonneuve P, Craxì A, Calleja J L
AO Fatebenefratelli e Oftalmico, Milano, Italy.
J Viral Hepat. 2015 May;22(5):469-80. doi: 10.1111/jvh.12342. Epub 2014 Oct 14.
In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/μL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile.
在许多国家，第一代蛋白酶抑制剂（PIs）/聚乙二醇干扰素/利巴韦林（P/R）仍是丙型肝炎病毒（HCV）感染患者的唯一治疗选择。患有晚期疾病且先前对P/R治疗失败的患者迫切需要治疗，但他们在临床试验中的代表性不足。在意大利-西班牙命名患者项目中接受博赛匹韦（BOC）+P/R治疗的所有有治疗经验的F3/4 Metavir患者均纳入本研究。采用多因素逻辑回归分析（MLR）来确定持续病毒学应答（SVR）和不良事件（AE）的基线及治疗期预测因素。分析了416例患者，平均年龄57.7岁（范围25 - 78岁），70%为男性，69.5%（289/416）为F4，14%（41/289）为Child-Pugh A6级，24%（70/289）有静脉曲张，42%（173/416）先前对P/R治疗无应答。总体而言，SVR率（所有381例接受一剂BOC的患者）为49%（F3患者中为58%，F4患者中为45%，复发患者中为61%，部分应答者中为51%，无应答者中为38%，治疗第8周（TW8）时HCV-RNA检测不到的患者中为72%）。在TW8时HCV-RNA≥1000 IU/L的患者中，SVR率为8%（阴性预测值 = 92%）。3例（0.8%）患者死亡，失代偿和感染分别见于2.9%和11%的患者。在MLR分析中，SVR的预测因素为TW4时HCV-RNA≥1log10、相对于基线下降、TW8时HCV-RNA检测不到、先前复发、白蛋白水平≥3.5 g/dL以及血小板计数≥100 000/μL。Metavir F4、Child-Pugh A6、白蛋白、血小板、年龄和女性性别与严重和血液学AE相关。在有治疗经验且符合基于干扰素治疗的晚期肝病患者中，TW8时的HCV-RNA可区分SVR可能性高或低的亚组。将TW8时的HCV-RNA作为无效标准，BOC/P/R似乎具有良好的效益风险比。
