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

BMJ 2009; 339 doi: http://dx.doi.org/10.1136/bmj.b5106 (Published 08 December 2009) Cite this as: BMJ 2009;339:b5106
  1. Tom Jefferson, researcher1,
  2. Mark Jones, statistician2,
  3. Peter Doshi, doctoral student3,
  4. Chris Del Mar, dean; coordinating editor of Cochrane Acute Respiratory Infections Group4
  1. 1Acute Respiratory Infections Group, Cochrane Collaboration, Rome, Italy
  2. 2University of Queensland, School of Population Health, Brisbane, Australia
  3. 3Program in History, Anthropology, Science, Technology and Society, Massachusetts Institute of Technology, Cambridge, MA, USA
  4. 4Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia
  1. Correspondence to: C Del Mar cdelmar{at}bond.edu.au
  • Accepted 26 November 2009

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.

Footnotes

  • We thank Liz Dooley, Dr Aoki, Jon Deeks, Carlo Di Pietrantonj, and Vittorio Demicheli for input and advice on earlier versions of this review; Liz Dooley, Janet Wale, John Bartlett, Sree Nair, Tom Fahey, Ruth Foxlee, and Alex Rivetti for help with the searches; and the Australian National Health and Medical Research Council and the UK NHS Research and Development fund for grants to enable this international rapid update.

  • Contributors: TOJ reapplied inclusion criteria for the 2009 update. All authors reappraised and investigated extracted data, while CDM supervised the process and arbitrated when necessary. MJ and PD checked and transformed data and supervised the revised meta-analysis. TOJ, CDM, MJ, and PD edited the text. All authors contributed to the final draft. CDM and TOJ are the guarantors.

  • Funding: This study was supported by grants from the Australian National Health and Medical Research Council and the UK NHS Research and Development fund.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that (1) CDM and TOJ have support from the UK National Institute for Health Research and the Australian National Health and Medical Research Council for the submitted work; (2) CDM has provided expert advice to GlaxoSmithKline about vaccination against acute otitis media; (3) their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (4) no authors have non-financial interests that may be relevant to the submitted work.

  • Ethical approval: Not required.

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