Neuraminidase inhibitors for preventing and treating influenza in healthy adults

Tom Jefferson, Mark Jones, Peter Doshi, Chris Del Mar, Liz Dooley, Ruth Foxlee

Research output: Contribution to journalReview articleResearchpeer-review

77 Citations (Scopus)

Abstract

BACKGROUND: Neuraminidase inhibitors (NI) are recommended for use against influenza and its complications in inter-pandemic years and during pandemics. OBJECTIVES: To assess the effects of NIs in preventing and treating influenza, its transmission, and its complications in otherwise healthy adults, and to estimate the frequency of adverse effects. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 3) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August 2009) and EMBASE (1980 to August 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised placebo-controlled trials of NIs in healthy adults exposed to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, assessed trial quality, and extracted data. We structured the comparisons into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose. MAIN RESULTS: We identified four prophylaxis, 12 treatment and four post-exposure prophylaxis trials. In prophylaxis compared to placebo, NIs had no effect against influenza-like illnesses (ILI) (risk ratio (RR) ranging from 1.28 for oral oseltamivir 75 mg daily to 0.76 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir against symptomatic influenza was 76% (at 75 mg daily), and 73% (at 150 mg daily). Inhaled zanamivir 10 mg daily performed similarly. Neither NI had a significant effect on asymptomatic influenza. Oseltamivir induced nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for post-exposure prophylaxis had an efficacy of 58% and 84% in two trials for households. Zanamivir performed similarly. The hazard ratios for time to alleviation of symptoms were in favour of the treated group 1.20 (1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Because of the exclusion of a review of mainly unpublished trials of oseltamivir, insufficient evidence remained to reach a conclusion on the prevention of complications requiring antibiotics in influenza cases (RR 0.57, 95% CI 0.23 to 1.37). Analysis of the US FDA and Japan's PMDA regulators' pharmacovigilance dataset, revealed incomplete reporting and description of harms preventing us from reaching firm conclusions on the central nervous system toxicity of neuraminidase inhibitors. AUTHORS' CONCLUSIONS: Numerous inconsistencies detected in the available evidence, followed by an inability to adequately access the data, has undermined confidence in our previous conclusions for oseltamivir. Independent RCTs to resolve these uncertainties are needed.
Original languageEnglish
Article numberCD001265
Pages (from-to)1-3
Number of pages3
JournalCochrane Database of Systematic Reviews
Volume2010
Issue number2
DOIs
Publication statusPublished - 21 Apr 2010

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Oseltamivir
Neuraminidase
Human Influenza
Zanamivir
Post-Exposure Prophylaxis
Randomized Controlled Trials
Odds Ratio
Pandemics
Placebos
Pharmacovigilance
MEDLINE
Respiratory Tract Infections
Nausea
Libraries
Uncertainty
Japan
Central Nervous System
Anti-Bacterial Agents
Therapeutics

Cite this

Jefferson, Tom ; Jones, Mark ; Doshi, Peter ; Del Mar, Chris ; Dooley, Liz ; Foxlee, Ruth. / Neuraminidase inhibitors for preventing and treating influenza in healthy adults. In: Cochrane Database of Systematic Reviews. 2010 ; Vol. 2010, No. 2. pp. 1-3.
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title = "Neuraminidase inhibitors for preventing and treating influenza in healthy adults",
abstract = "BACKGROUND: Neuraminidase inhibitors (NI) are recommended for use against influenza and its complications in inter-pandemic years and during pandemics. OBJECTIVES: To assess the effects of NIs in preventing and treating influenza, its transmission, and its complications in otherwise healthy adults, and to estimate the frequency of adverse effects. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 3) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August 2009) and EMBASE (1980 to August 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised placebo-controlled trials of NIs in healthy adults exposed to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, assessed trial quality, and extracted data. We structured the comparisons into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose. MAIN RESULTS: We identified four prophylaxis, 12 treatment and four post-exposure prophylaxis trials. In prophylaxis compared to placebo, NIs had no effect against influenza-like illnesses (ILI) (risk ratio (RR) ranging from 1.28 for oral oseltamivir 75 mg daily to 0.76 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir against symptomatic influenza was 76{\%} (at 75 mg daily), and 73{\%} (at 150 mg daily). Inhaled zanamivir 10 mg daily performed similarly. Neither NI had a significant effect on asymptomatic influenza. Oseltamivir induced nausea (odds ratio (OR) 1.79, 95{\%} CI 1.10 to 2.93). Oseltamivir for post-exposure prophylaxis had an efficacy of 58{\%} and 84{\%} in two trials for households. Zanamivir performed similarly. The hazard ratios for time to alleviation of symptoms were in favour of the treated group 1.20 (1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Because of the exclusion of a review of mainly unpublished trials of oseltamivir, insufficient evidence remained to reach a conclusion on the prevention of complications requiring antibiotics in influenza cases (RR 0.57, 95{\%} CI 0.23 to 1.37). Analysis of the US FDA and Japan's PMDA regulators' pharmacovigilance dataset, revealed incomplete reporting and description of harms preventing us from reaching firm conclusions on the central nervous system toxicity of neuraminidase inhibitors. AUTHORS' CONCLUSIONS: Numerous inconsistencies detected in the available evidence, followed by an inability to adequately access the data, has undermined confidence in our previous conclusions for oseltamivir. Independent RCTs to resolve these uncertainties are needed.",
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Neuraminidase inhibitors for preventing and treating influenza in healthy adults. / Jefferson, Tom; Jones, Mark; Doshi, Peter; Del Mar, Chris; Dooley, Liz; Foxlee, Ruth.

In: Cochrane Database of Systematic Reviews, Vol. 2010, No. 2, CD001265, 21.04.2010, p. 1-3.

Research output: Contribution to journalReview articleResearchpeer-review

TY - JOUR

T1 - Neuraminidase inhibitors for preventing and treating influenza in healthy adults

AU - Jefferson, Tom

AU - Jones, Mark

AU - Doshi, Peter

AU - Del Mar, Chris

AU - Dooley, Liz

AU - Foxlee, Ruth

PY - 2010/4/21

Y1 - 2010/4/21

N2 - BACKGROUND: Neuraminidase inhibitors (NI) are recommended for use against influenza and its complications in inter-pandemic years and during pandemics. OBJECTIVES: To assess the effects of NIs in preventing and treating influenza, its transmission, and its complications in otherwise healthy adults, and to estimate the frequency of adverse effects. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 3) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August 2009) and EMBASE (1980 to August 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised placebo-controlled trials of NIs in healthy adults exposed to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, assessed trial quality, and extracted data. We structured the comparisons into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose. MAIN RESULTS: We identified four prophylaxis, 12 treatment and four post-exposure prophylaxis trials. In prophylaxis compared to placebo, NIs had no effect against influenza-like illnesses (ILI) (risk ratio (RR) ranging from 1.28 for oral oseltamivir 75 mg daily to 0.76 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir against symptomatic influenza was 76% (at 75 mg daily), and 73% (at 150 mg daily). Inhaled zanamivir 10 mg daily performed similarly. Neither NI had a significant effect on asymptomatic influenza. Oseltamivir induced nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for post-exposure prophylaxis had an efficacy of 58% and 84% in two trials for households. Zanamivir performed similarly. The hazard ratios for time to alleviation of symptoms were in favour of the treated group 1.20 (1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Because of the exclusion of a review of mainly unpublished trials of oseltamivir, insufficient evidence remained to reach a conclusion on the prevention of complications requiring antibiotics in influenza cases (RR 0.57, 95% CI 0.23 to 1.37). Analysis of the US FDA and Japan's PMDA regulators' pharmacovigilance dataset, revealed incomplete reporting and description of harms preventing us from reaching firm conclusions on the central nervous system toxicity of neuraminidase inhibitors. AUTHORS' CONCLUSIONS: Numerous inconsistencies detected in the available evidence, followed by an inability to adequately access the data, has undermined confidence in our previous conclusions for oseltamivir. Independent RCTs to resolve these uncertainties are needed.

AB - BACKGROUND: Neuraminidase inhibitors (NI) are recommended for use against influenza and its complications in inter-pandemic years and during pandemics. OBJECTIVES: To assess the effects of NIs in preventing and treating influenza, its transmission, and its complications in otherwise healthy adults, and to estimate the frequency of adverse effects. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 3) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August 2009) and EMBASE (1980 to August 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised placebo-controlled trials of NIs in healthy adults exposed to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, assessed trial quality, and extracted data. We structured the comparisons into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose. MAIN RESULTS: We identified four prophylaxis, 12 treatment and four post-exposure prophylaxis trials. In prophylaxis compared to placebo, NIs had no effect against influenza-like illnesses (ILI) (risk ratio (RR) ranging from 1.28 for oral oseltamivir 75 mg daily to 0.76 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir against symptomatic influenza was 76% (at 75 mg daily), and 73% (at 150 mg daily). Inhaled zanamivir 10 mg daily performed similarly. Neither NI had a significant effect on asymptomatic influenza. Oseltamivir induced nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for post-exposure prophylaxis had an efficacy of 58% and 84% in two trials for households. Zanamivir performed similarly. The hazard ratios for time to alleviation of symptoms were in favour of the treated group 1.20 (1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Because of the exclusion of a review of mainly unpublished trials of oseltamivir, insufficient evidence remained to reach a conclusion on the prevention of complications requiring antibiotics in influenza cases (RR 0.57, 95% CI 0.23 to 1.37). Analysis of the US FDA and Japan's PMDA regulators' pharmacovigilance dataset, revealed incomplete reporting and description of harms preventing us from reaching firm conclusions on the central nervous system toxicity of neuraminidase inhibitors. AUTHORS' CONCLUSIONS: Numerous inconsistencies detected in the available evidence, followed by an inability to adequately access the data, has undermined confidence in our previous conclusions for oseltamivir. Independent RCTs to resolve these uncertainties are needed.

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U2 - 10.1002/14651858.CD001265.pub3

DO - 10.1002/14651858.CD001265.pub3

M3 - Review article

VL - 2010

SP - 1

EP - 3

JO - Cochrane database of systematic reviews (Online)

JF - Cochrane database of systematic reviews (Online)

SN - 1469-493X

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M1 - CD001265

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