在接受阿片类药物替代治疗的慢性丙型肝炎基因型 1-6 患者中，glecaprevir/pibrentasvir 的安全性和疗效。
Safety and efficacy of glecaprevir/pibrentasvir in patients with chronic hepatitis C genotypes 1-6 receiving opioid substitution therapy.
机构信息
The Kirby Institute, UNSW Sydney, Sydney, Australia.
The Kirby Institute, UNSW Sydney, Sydney, Australia.
出版信息
Int J Drug Policy. 2019 Apr;66:73-79. doi: 10.1016/j.drugpo.2019.01.011. Epub 2019 Feb 6.
BACKGROUND
International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST.
METHODS
Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST.
RESULTS
Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12.
CONCLUSION
Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST.
背景
国际指南建议对包括正在接受阿片类药物替代治疗（OST）的药物滥用者（PWID）在内的丙型肝炎病毒（HCV）感染者进行治疗。在临床试验中，泛基因型组合 glecaprevir 和 pibrentasvir 在治疗后第 12 周（SVR12）时表现出高持续病毒学应答。在此，我们评估 glecaprevir/pibrentasvir 在接受 OST 的患者中的安全性和疗效。
方法
在八项 2 期和 3 期试验中，对接受 glecaprevir/pibrentasvir 治疗 8、12 或 16 周的 1-6 型 HCV 基因型患者进行汇总分析，并根据是否接受 OST 进行分组。对接受和未接受 OST 的患者进行治疗完成情况、治疗依从性、SVR12、不良事件（AE）和实验室异常评估。
结果
在 2256 名患者中，有 157 名（7%）正在接受 OST。与未接受 OST 的患者相比，接受 OST 的患者年龄较小（平均年龄 46.8 岁 vs 52.8 岁）、男性（69% vs 54%）、白人（93% vs 80%）、HCV 初治（86% vs 72%）、丙型肝炎基因型 3 型（60% vs 26%）和有抑郁或双相障碍病史（43% vs 19%）。大多数患者完成（OST：98%[n/N=154/157]；非 OST：99%[n/N=2070/2099]）并对 glecaprevir/pibrentasvir 治疗有很好的依从性（接受≥90%的研究药物剂量）（OST：98%[n/N=121/123]；非 OST：99%[n/N=1884/1905]，数据可用患者）。在意向治疗人群中，OST 和非 OST 患者的 SVR12 率分别为 96.2%（n/N=151/157；95%CI 93.2-99.2）和 97.9%（n/N=2055/2099；95%CI 97.3-98.5）。对于 OST 患者，无应答的原因包括病毒学复发（<1%；n=1）、过早停药（<1%；n=1）和失访（3%；n=4）。在接受 OST 的患者中发生率≥10%的 AE 包括头痛、疲劳和恶心。在两组中，药物相关严重 AE、导致停药的 AE 和 3 级或更高的实验室异常均不常见（<1%）。未发生 HCV 再感染。
结论
在接受 OST 的 HCV 感染患者中，glecaprevir/pibrentasvir 疗效显著且耐受性良好。
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