Monto A S, Webster A, Keene O
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
J Antimicrob Chemother. 1999 Nov;44 Suppl B:23-9. doi: 10.1093/jac/44.suppl_2.23.
Zanamivir, a potent, highly selective inhibitor of influenza virus A and B neuraminidase, has been evaluated in seven, similarly designed, placebo-controlled studies of the treatment of influenza. Patients with typical influenza symptoms were recruited when influenza was known to be circulating in the community. Six of these studies included a zanamivir 10 mg inhaled bd (for 5 days) treatment arm, the dose regimen submitted to regulatory agencies. Pooled analyses were conducted to evaluate efficacy more precisely in terms of the alleviation of symptoms in population subgroups and for secondary endpoints. Median time to alleviation of symptoms, the primary endpoint, was reduced from 6.0 days in the placebo group (n = 1,102) to 5.0 days in the zanamivir group (n = 1,133), P< 0.001. In febrile, laboratory-confirmed, influenza-positive (IP) patients, time to alleviation was reduced from 6.5 days to 5.0 days, a treatment benefit of 1.5 days (P < 0.001). A larger treatment benefit (3 days) was seen in IP patients who had severe symptoms at entry (n = 474, P < 0.001), compared with 1 day in patients whose symptoms were not severe (n = 1,098, P< 0.001). Similarly, a 3 day treatment benefit (P = 0.003) was observed in IP patients aged >50 years (n = 263), compared with 1 day (P < 0.001) in patients aged <50 years. In 'high-risk' IP patients (recruited into all treatment studies), there was a treatment benefit of 2.5 days (n = 305, P = 0.006). Pooled analyses of secondary endpoints showed statistically significant reductions in antibiotic use, time to return to normal activities and use of relief medication. In addition, reductions in symptom scores were apparent shortly after commencing zanamivir treatment. By the evening of the second day of treatment, the median total symptom score had fallen by 44% in zanamivir recipients compared with 33% in placebo recipients (P < 0.001). These results highlight the groups likely to show greatest benefit from zanamivir treatment, and confirm the clinical relevance of the treatment benefit.
扎那米韦是一种强效、高选择性的甲型和乙型流感病毒神经氨酸酶抑制剂，已在七项设计相似、以安慰剂为对照的流感治疗研究中进行了评估。当已知流感在社区中传播时，招募有典型流感症状的患者。其中六项研究包括一个扎那米韦10毫克吸入剂，每日两次（共5天）的治疗组，这是提交给监管机构的给药方案。进行汇总分析以更精确地评估在人群亚组症状缓解方面以及次要终点的疗效。主要终点症状缓解的中位时间从安慰剂组（n = 1102）的6.0天降至扎那米韦组（n = 1133）的5.0天，P < 0.001。在发热、实验室确诊的流感阳性（IP）患者中，症状缓解时间从6.5天降至5.0天，治疗获益为1.5天（P < 0.001）。与症状不严重的患者（n = 1098，P < 0.001）的1天相比，在入组时症状严重的IP患者（n = 474，P < 0.001）中观察到更大的治疗获益（3天）。同样，在年龄>50岁的IP患者（n = 263）中观察到3天的治疗获益（P = 0.003），而在年龄<50岁的患者中为1天（P < 0.001）。在“高危”IP患者（纳入所有治疗研究）中，治疗获益为2.5天（n = 305，P = 0.006）。次要终点的汇总分析显示，抗生素使用、恢复正常活动时间和缓解药物使用均有统计学显著减少。此外，在开始扎那米韦治疗后不久，症状评分就明显降低。到治疗第二天晚上，扎那米韦治疗组的总症状中位评分下降了44%，而安慰剂组为33%（P < 0.001）。这些结果突出了可能从扎那米韦治疗中获益最大的人群，并证实了治疗获益的临床相关性。
