Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis

Jefferson, Tom, Jones, Mark, Doshi, Peter and Del Mar, Chris (2009) Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ, 339 7734: 1-8. doi:10.1136/bmj.b5106


Author Jefferson, Tom
Jones, Mark
Doshi, Peter
Del Mar, Chris
Title Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis
Journal name BMJ
ISSN 0959-8138
0959-535X
Publication date 2009-12-01
Sub-type Article (original research)
DOI 10.1136/bmj.b5106
Open Access Status DOI
Volume 339
Issue 7734
Start page 1
End page 8
Total pages 8
Editor Trevor Jackson
Place of publication London, United Kingdom
Publisher B M J
Collection year 2010
Language eng
Formatted abstract
Objectives: To update a 2005 Cochrane review that assessed the effects of neuraminidase inhibitors in preventing or ameliorating the symptoms of influenza, the transmission of influenza, and complications from influenza in healthy adults, and to estimate the frequency of adverse effects.

Search strategy: An updated search of the Cochrane central register of controlled trials (Cochrane Library 2009, issue 2), which contains the Acute Respiratory Infections Group’s specialised register, Medline (1950-Aug 2009), Embase (1980-Aug 2009), and post-marketing pharmacovigilance data and comparative safety cohorts.

Selection criteria: Randomised placebo controlled studies of neuraminidase inhibitors in otherwise healthy adults exposed to naturally occurring influenza.

Main outcome measures: Duration and incidence of symptoms; incidence of lower respiratory tract infections, or their proxies; and adverse events.

Data extraction: Two reviewers applied inclusion criteria, assessed trial quality, and extracted data.

Data analysis: Comparisons were structured into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose.

Results: 20 trials were included: four on prophylaxis, 12 on treatment, and four on postexposure prophylaxis. For prophylaxis, neuraminidase inhibitors had no effect against influenza-like illness or asymptomatic influenza. The efficacy of oral oseltamivir against symptomatic laboratory confirmed influenza was 61% (risk ratio 0.39, 95% confidence interval 0.18 to 0.85) at 75 mg daily and 73% (0.27, 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily was 62% efficacious (0.38, 0.17 to 0.85). Oseltamivir for postexposure prophylaxis had an efficacy of 58% (95% confidence interval 15% to 79%) and 84% (49% to 95%) in two trials of households. Zanamivir performed similarly. The hazard ratios for time to alleviation of influenza-like illness symptoms were in favour of treatment: 1.20 (95% confidence interval 1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Eight unpublished studies on complications were ineligible and therefore excluded. The remaining evidence suggests oseltamivir did not reduce influenza related lower respiratory tract complications (risk ratio 0.55, 95% confidence interval 0.22 to 1.35). From trial evidence, oseltamivir induced nausea (odds ratio 1.79, 95% confidence interval 1.10 to 2.93). Evidence of rarer adverse events from pharmacovigilance was of poor quality or possibly under-reported.

Conclusion: Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza. Independent randomised trials to resolve these uncertainties are needed.
Keyword Randomized controlled trial
B virus-infections
Inhaled zanamivir
Oseltamivir treatment
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Print version: BMJ: Clinical research edition. Article also published in the BMJ: International Edition. Volume 339, Issue 7734, 22 December 2009, Page 1364

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
ERA 2012 Admin Only
School of Public Health Publications
 
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Created: Sun, 27 Dec 2009, 10:04:07 EST