CRC "A. M. and A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Liver Section, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), HepaC cohort, UAB (Universitat Autonoma de Barcelona), Barcelona, Spain.
J Hepatol. 2020 Jun;72(6):1112-1121. doi: 10.1016/j.jhep.2020.01.025. Epub 2020 Feb 13.
BACKGROUND & AIMS: Glecaprevir/pibrentasvir is approved for treating adults infected with HCV genotypes 1-6. In clinical trials, glecaprevir/pibrentasvir was associated with high rates of sustained virologic response at post-treatment week 12 (SVR12) and was well tolerated. A systematic review and meta-analysis of the real-world effectiveness and safety of glecaprevir/pibrentasvir were undertaken.
Real-world studies reporting SVR12 in adults with HCV infection (n ≥20) treated with glecaprevir/pibrentasvir were identified in journal publications from January 1, 2017, to February 25, 2019, and congress presentations through April 14, 2019. Random-effects meta-analysis was used to determine SVR12 rates using data from ≥2 cohorts; intention-to-treat (ITT) analyses included patients treated with glecaprevir/pibrentasvir who had SVR12 data available, discontinued early, or were lost to follow-up; modified ITT (mITT) analyses excluded those with non-virologic failure. Naïve pooling was used to calculate adverse event (AE) rates.
Overall, 12,531 adults were treated with glecaprevir/pibrentasvir (18 cohorts). Of patients with post-treatment week 12 data, SVR12 rates were 96.7% (95% CI 95.4-98.1) in the ITT population (n = 8,583, 15 cohorts) and 98.1% (95% CI 97.1-99.2) in the mITT population (n = 7,001, 14 cohorts). SVR12 rates were ≥95% across subgroups (HCV genotype, cirrhosis status, treatment history, treatment duration, on-label treatment, and subgroups of interest). AEs were reported in 17.7% (1,271/7,199) of patients (8 cohorts). Serious AEs were reported in 1.0% (55/5,522) of patients (6 cohorts). The most frequent AEs were pruritus, fatigue, and headache. AE-related treatment discontinuations were reported in 0.6% (33/5,595) of patients (6 cohorts).
Consistent with clinical trials, real-world evidence indicates that glecaprevir/pibrentasvir is a well-tolerated and highly effective pangenotypic treatment for a broad range of HCV-infected patients.
It is important to assess treatments for hepatitis C virus (HCV) in the real world, as patient populations tend to be more diverse and potentially less adherent to treatment compared to those in clinical trials. Results from 18 studies performed in real-world clinics were pooled and analyzed to investigate the effectiveness and safety of a direct-acting antiviral combination (glecaprevir/pibrentasvir) in routine clinical practice. This analysis showed that glecaprevir/pibrentasvir is highly effective and well tolerated across all HCV genotypes and patient groups studied. It also showed that results seen in the real world are similar to the results seen in clinical trials, even in patients historically considered more challenging to treat.
格卡瑞韦哌仑他韦适用于治疗感染 HCV 基因型 1-6 的成人患者。在临床试验中，格卡瑞韦哌仑他韦治疗后第 12 周持续病毒学应答（SVR12）的比例很高，且具有良好的耐受性。本文对格卡瑞韦哌仑他韦在真实世界中的有效性和安全性进行了系统评价和荟萃分析。
检索 2017 年 1 月 1 日至 2019 年 2 月 25 日、2019 年 4 月 14 日前在期刊发表的文章和会议报告中关于使用格卡瑞韦哌仑他韦治疗 HCV 感染成人患者（≥20 例）的真实世界研究，收集 SVR12 相关数据。使用≥2 个队列的数据进行随机效应荟萃分析，确定 SVR12 比例；意向治疗（ITT）分析包括接受格卡瑞韦哌仑他韦治疗、有 SVR12 数据、早期停药或失访的患者；改良 ITT（mITT）分析排除非病毒学失败患者。采用-naive 法计算不良反应（AE）发生率。
共纳入 12531 例接受格卡瑞韦哌仑他韦治疗的成年患者（18 个队列）。接受治疗后第 12 周数据评估的患者中，ITT 人群（n=8583，15 个队列）和 mITT 人群（n=7001，14 个队列）的 SVR12 比例分别为 96.7%（95%CI 95.4-98.1）和 98.1%（95%CI 97.1-99.2）。在所有亚组（HCV 基因型、肝硬化状态、治疗史、治疗持续时间、适应证内治疗和关注亚组）中，SVR12 比例均≥95%。17.7%（7199/40434）的患者（8 个队列）报告了 AE。1.0%（55/5522）的患者（6 个队列）报告了严重 AE。最常见的 AE 为瘙痒、疲劳和头痛。报告了 0.6%（33/5595）的 AE 相关治疗中断（6 个队列）。
与临床试验结果一致，真实世界证据表明，格卡瑞韦哌仑他韦是一种对广泛 HCV 感染患者耐受性良好且高度有效的泛基因型治疗药物。
