NYU Langone Health, New York, New York, USA.
Campus Stuivenberg, Antwerp, Belgium.
J Viral Hepat. 2023 May;30(5):448-454. doi: 10.1111/jvh.13814. Epub 2023 Mar 2.
To evaluate the safety and tolerability of the fixed-dose, single-tablet regimen sofosbuvir/velpatasvir (SOF/VEL) for the treatment of hepatitis C virus (HCV) infection in three Phase 3 studies in patients with and without compensated cirrhosis. Data from three registrational trials (ASTRAL-1, NCT02201940; ASTRAL-2, NCT02220998; ASTRAL-3, NCT02201953) were pooled by treatment regimen. Researchers assessed treatment-emergent adverse events (TEAEs) and laboratory abnormalities in patients randomized to SOF/VEL or placebo for 12 weeks in ASTRAL-1 and SOF/VEL for 12 weeks in ASTRAL-2 and ASTRAL-3. Overall, 1035 patients were treated with SOF/VEL, and 116 patients received placebo. Rates of any TEAE were generally similar between patients receiving SOF/VEL (79.4%) and those receiving placebo (76.7%). The majority of TEAEs were mild to moderate, with 23 (2.2%) treatment-emergent serious AEs in patients treated with SOF/VEL. Of these treatment-emergent serious AEs, none led to premature study discontinuation, nor were they considered related to treatment. Presence of compensated cirrhosis, greater age and mild renal impairment did not impact incidence or severity of TEAEs with SOF/VEL treatment. The most common TEAEs (incidence ≥10%) were headache, fatigue, nausea and nasopharyngitis in patients receiving SOF/VEL; similar rates were observed in placebo-treated patients. Three deaths (<1%) were reported in patients treated with SOF/VEL, all posttreatment and none assessed as related to study treatment. Similar to that of placebo, SOF/VEL treatment of HCV infection had a safety/tolerability profile that was not affected by baseline factors, such as the presence of compensated cirrhosis, mild renal impairment or advanced age.
评估固定剂量、单片制剂索磷布韦/维帕他韦（SOF/VEL）治疗伴有或不伴有代偿性肝硬化的丙型肝炎病毒（HCV）感染的安全性和耐受性。对三项注册试验（ASTRAL-1，NCT02201940；ASTRAL-2，NCT02220998；ASTRAL-3，NCT02201953）的数据，按治疗方案进行了汇总。研究者评估了 1035 例接受 SOF/VEL 治疗 12 周的患者和 116 例接受安慰剂治疗的患者的治疗期间出现的不良事件（TEAEs）和实验室异常。SOF/VEL 治疗 12 周的 ASTRAL-2 和 ASTRAL-3。总体而言，1035 例患者接受 SOF/VEL 治疗，116 例患者接受安慰剂治疗。接受 SOF/VEL 治疗的患者（79.4%）和接受安慰剂治疗的患者（76.7%）的任何 TEAEs 发生率基本相似。大多数 TEAEs 为轻至中度，SOF/VEL 治疗的患者中共有 23 例（2.2%）治疗期间出现严重不良事件。这些治疗期间出现的严重不良事件中，没有一起导致研究提前终止，也没有被认为与治疗有关。代偿性肝硬化、年龄较大和轻度肾功能损害不影响 SOF/VEL 治疗的 TEAEs 发生率或严重程度。SOF/VEL 治疗的患者最常见的 TEAEs（发生率≥10%）为头痛、疲劳、恶心和鼻咽炎；接受安慰剂治疗的患者也观察到类似的发生率。SOF/VEL 治疗的患者中报告了 3 例（<1%）死亡，均在治疗后发生，均未评估与研究治疗相关。SOF/VEL 治疗 HCV 感染的安全性/耐受性与安慰剂相似，不受基线因素（如代偿性肝硬化、轻度肾功能损害或年龄较大）的影响。
