Clinical effectiveness of four neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) for children with influenza A and B in the 2014–2015 to 2016–2017 influenza seasons in Japan

Abstract

The clinical effectiveness of four neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir, and peramivir) for children aged 0 months to 18 years with influenza A and B were investigated in the 2014-2015 to 2016-2017 influenza seasons in Japan. A total of 1207 patients (747 with influenza A and 460 with influenza B) were enrolled. The Cox proportional-hazards model using all of the patients showed that the duration of fever after administration of the first dose of the NAI was shorter in older patients (hazard ratio = 1.06 per 1 year of age, p< 0.001) and that the duration of fever after administration of the first dose of the NAI was shorter in patients with influenza A infection than in patients with influenza B infection (hazard ratio = 2.21, p < 0.001). A logistic regression model showed that the number of biphasic fever episodes was 2.99-times greater for influenza B-infected patients than for influenza A-infected patients (p < 0.001). The number of biphasic fever episodes in influenza A- or B-infected patients aged 0-4 years was 2.89-times greater than that in patients aged 10-18 years (p = 0.010), and the number of episodes in influenza A- or B-infected patients aged 5-9 years was 2.13-times greater than that in patients aged 10-18 years (p = 0.012).

Effectiveness of four types of neuraminidase inhibitors approved in Japan for the treatment of influenza

“…The average age for the peramivir treatment group (6.0 ± 4.4 years) was the lowest, because this drug was more used for younger children when oral or inhalation medication was difficult. Although the number of patients in the peramivir group was low and the statistical power was lacking, we retained the peramivir treatment group in our analysis because the clinical effectiveness of peramivir in outpatients has rarely been reported [24, 25]. The patient characteristics for influenza A/H3N2 and B were similar to those for A/H1N1pdm09, for all categories.…”

“…Laninamivir is a single dose, long-acting drug that is administered by inhalation, while oseltamivir and zanamivir are administered twice daily for 5 days. Ishiguro et al reported that fever duration in laninamivir-treated influenza A or B infections was longer compared to oseltamivir or peramivir-treated infections among outpatients aged 0–18 years using Cox-proportional hazard model [24]. Koseki et al reported that the frequency of biphasic fever was significantly higher in laninamivir-treated patients than in zanamivir-treated patients, although the fever duration for zanamivir and laninamivir was not significantly different among patients aged 5 to 18 years [31].…”

“…Sugaya et al reported a significantly shorter fever duration (0.75 to 1.10 day) in patients administerd peramivir than in those administered laninamivir (P<0.05) among influenza A/H3N2 or A/H1N1pdm09 infections [33]. Ishiguro et al suggested the possibility that an inadequate inhalation of the single dose laninamivir influenced the longer fever duration in patients aged 5 to 9 years than those treated with other NAIs [24]. Koseki et al also suggested that incomplete inhalation of the single dose of laninamivir, especially in young children, could explain the increase in frequency of biphasic fever in the laninamivir treated group compared with zanamivir treated group [31].…”

A Meta-Analysis Comparing the Efficacy and Safety of Peramivir with Other Neuraminidase Inhibitors for Influenza Treatment

“…Nine articles were excluded because they were review articles [5,[8][9][10][11][12][13][14][15]] and 3 articles were excluded because they did not compare peramivir with other NAIs [16][17][18]. Furthermore, one study was excluded because of crossover treatment [19] and the other one was excluded because of lack of data [20]. Finally, a total of 12 articles with complete data were selected for this meta-analysis ( Figure 1).…”

A Review of Therapeutics in Clinical Development for Respiratory Syncytial Virus and Influenza in Children

“…49 There is also a concern that in children with poor inspiratory effort, the delivery of laninamivir may require increased dosages. 51,52 Finally, baloxavir marboxil is an endonuclease inhibitor that targets the viral polymerase complex and inhibits mRNA synthesis and viral transcription. 53 It has recently been evaluated in two Phase III clinical trials, one in adults and adolescents with uncomplicated influenza infection (completed in 2017), and one in adults and adolescents at high risk for complications from influenza (ongoing).…”