Neuraminidase inhibitors for preventing and treating influenza in children
(published trials only).
Author(s): Wang K, Shun-Shin M, Gill P, Perera R, Harnden A.
Affiliation(s): Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Publication date & source: 2012, Cochrane Database Syst Rev. , 4:CD002744
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.
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