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Meta-Analysis
. 2012 Apr 18;2012(4):CD002744.
doi: 10.1002/14651858.CD002744.pub4.

Neuraminidase inhibitors for preventing and treating influenza in children (published trials only)

Kay Wang  1 , Matthew Shun-Shin, Peter Gill, Rafael Perera, Anthony Harnden
Affiliations
Meta-Analysis

Neuraminidase inhibitors for preventing and treating influenza in children (published trials only)

Kay Wang et al. Cochrane Database Syst Rev. .

Abstract

Background: During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed.

Objectives: To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children.

Search methods: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011).

Selection criteria: Double-blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies.

Data collection and analysis: Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir.

Main results: Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near-patient influenza testing were included. Of these 2356 children, 1255 had laboratory-confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory-confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir-resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory-confirmed influenza (risk difference (RD) -0.14, 95% confidence interval (CI) -0.24 to -0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD -0.08, 95% CI -0.12 to -0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar.

Authors' conclusions: Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.

PubMed Disclaimer

Conflict of interest statement

No funding source nor sponsor had any role in any aspect of this study. None of the authors declare a conflict of interest.

Figures

1
1
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Zanamivir and oseltamivir, Outcome 1 Time to resolution of cough.
1.2
1.2. Analysis
Comparison 1 Zanamivir and oseltamivir, Outcome 2 Incidence of asthma exacerbations in those with confirmed influenza.
1.3
1.3. Analysis
Comparison 1 Zanamivir and oseltamivir, Outcome 3 Incidence of otitis media in those with clinical influenza.
1.4
1.4. Analysis
Comparison 1 Zanamivir and oseltamivir, Outcome 4 Incidence of otitis media in those with confirmed influenza.
1.5
1.5. Analysis
Comparison 1 Zanamivir and oseltamivir, Outcome 5 Use of antibiotics in those with confirmed influenza.
1.6
1.6. Analysis
Comparison 1 Zanamivir and oseltamivir, Outcome 6 Incidence of confirmed influenza in contacts of those with clinical influenza.
1.7
1.7. Analysis
Comparison 1 Zanamivir and oseltamivir, Outcome 7 Adverse events in those with clinical influenza.
2.1
2.1. Analysis
Comparison 2 Laninamivir and oseltamivir, Outcome 1 Adverse events.
See this image and copyright information in PMC

Update of

References

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Chik 2004 {published data only}
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NV16871 {unpublished data only}
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NV20236 {published data only}
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Okamoto 2005 {published data only}
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References to studies awaiting assessment

ISRCTN43083885 {published data only}
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References to other published versions of this review

Matheson 2003
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