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[e-med] Méta-analyse publiée par le BMJ : oseltamivir et zanamivir de la grippe

Published 8 December 2009, doi:10.1136/bmj.b5106
Cite this as: BMJ 2009;339:b5106

Neuraminidase inhibitors for preventing and treating influenza in healthy
adults: systematic review and meta-analysis
Tom Jefferson, researcher1, Mark Jones, statistician2, Peter Doshi, doctoral
student3, Chris Del Mar, dean; coordinating editor of Cochrane Acute
Respiratory Infections Group4

1 Acute Respiratory Infections Group, Cochrane Collaboration, Rome, Italy, 2
University of Queensland, School of Population Health, Brisbane, Australia,
3 Program in History, Anthropology, Science, Technology and Society,
Massachusetts Institute of Technology, Cambridge, MA, USA, 4 Faculty of
Health Sciences and Medicine, Bond University, Gold Coast, Australia


Correspondence to: C Del Mar cdelmar@bond.edu.au


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

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.

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