Whitley Richard, Laughlin Alan, Carson Simon, Mitha Essack, Tellier Guy, Stich Mark, Elder Jenna, Alexander W James, Dobo Sylvia, Collis Phil, Sheridan William P
Pediatric Infectious Diseases, University of Alabama, Birmingham, AL, USA.
Antivir Ther. 2015;20(7):709-19. doi: 10.3851/IMP2874. Epub 2014 Oct 15.
Current influenza treatment options include oral or inhaled antiviral agents. There is an unmet need for parenteral antiviral treatments.
Peramivir, a parenteral influenza neuraminidase inhibitor (NAI), was administered by single-dose intramuscular (IM) injection in two placebo-controlled studies in adult outpatients with acute, uncomplicated influenza during two consecutive influenza seasons.
In a Phase II study, peramivir treatment significantly shortened duration of fever and reduced viral load in nasopharyngeal secretions. A subsequent Phase III study was not fully enrolled; however, in both studies, the magnitude of the treatment effect favouring peramivir was consistent with that reported for other NAIs. A post-hoc analysis was conducted by integrating efficacy and safety results of 427 subjects from both studies. The median time to alleviation of symptoms (TTAS) in subjects receiving peramivir 300 mg (113.2 h) was shorter than for placebo (134.8 h; P=0.161 adjusted for smoking behaviour, influenza season and virus type; unadjusted P=0.047). The median time to resolution of fever was reduced by 24 h after treatment with peramivir 300 mg compared with placebo (P=0.004). The proportion of subjects shedding influenza virus was significantly decreased over 48 h following peramivir treatment (P=0.009). Detection of post-treatment viruses with decreased susceptibility to NAIs was uncommon. Peramivir was generally safe and well-tolerated with types and rates of adverse event similar to placebo.
The results of these studies are consistent with previous reports of peramivir administered by intravenous infusion, and demonstrate a positive risk-benefit profile for peramivir in patients with acute uncomplicated influenza.
目前的流感治疗选择包括口服或吸入抗病毒药物。胃肠外抗病毒治疗仍有未满足的需求。
在两个连续的流感季节中，对成年急性、无并发症流感门诊患者进行了两项安慰剂对照研究，通过单剂量肌内注射给予胃肠外流感神经氨酸酶抑制剂（NAI）帕拉米韦。
在一项II期研究中，帕拉米韦治疗显著缩短了发热持续时间并降低了鼻咽分泌物中的病毒载量。随后的一项III期研究未完全入组；然而，在两项研究中，支持帕拉米韦的治疗效果幅度与其他NAI报道的一致。通过整合两项研究中427名受试者的疗效和安全性结果进行了事后分析。接受300mg帕拉米韦治疗的受试者症状缓解的中位时间（TTAS）（113.2小时）比安慰剂组（134.8小时；根据吸烟行为、流感季节和病毒类型调整后P = 0.161；未调整P = 0.047）短。与安慰剂相比，300mg帕拉米韦治疗后发热消退的中位时间缩短了24小时（P = 0.004）。帕拉米韦治疗后48小时内流感病毒脱落的受试者比例显著降低（P = 0.009）。检测到对NAI敏感性降低的治疗后病毒并不常见。帕拉米韦总体安全且耐受性良好，不良事件的类型和发生率与安慰剂相似。
这些研究结果与先前关于静脉输注帕拉米韦的报道一致，并证明了帕拉米韦在急性无并发症流感患者中具有良好的风险效益比。
