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

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. 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 Eight unpublished studies on complications were ineligible and therefore excluded.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.

Big pharma under the spotlight

“…Jefferson never received the study reports, and the Cochrane review published 2 months later in the BMJ [6] said that because 8 of the 10 randomised controlled trials on which effectiveness claims were based were never published, the evidence could not be relied on. The 2 published studies were funded by Roche and authored by Roche employees and external experts paid by Roche.…”

“…In that year, Roche made a public promise to release full trial reports for Tamiflu, in response to an investigation by the BMJ and Cochrane collaborators Peter Doshi and Tom Jefferson. [3][4][5][6] In September 2009 Jefferson asked Roche for the unpublished data set that Roche used in an analysis published in 2003, for use the following month to update the Cochrane Collaboration's review on neuraminidase inhibitors in healthy adults. After asking Jefferson to sign a confidentiality agreement promising that he would not publish the data in full, Roche declined to supply the data set because they had also been approached by another group doing a similar meta-analysis and didn't want conflict.…”

Influenza pandêmica A (H1N1) 2009: fatores de risco para o internamento

“…However, the severity of the disease can be affected by different geographic contexts and seasonal conditions, and can also vary depending on whether or not the virus will adapt to its new host. (5)(6)(7)(8)(9) The leading causes of mortality are related to respiratory impairment, which increases the clinical severity of the infection. The significant respiratory impairment associated with severe cases of influenza is described as severe acute respiratory syndrome.…”

The characteristics, clinical manifestations and outcomes of pandemic influenza A (H1N1) 2009 in the elderly

“…Evolution of the disease is usually benign and self-limiting, and a reduction in symptoms usually occurs in an average of three days [7][8][9][10][11] . However, in the elderly, very young children, and individuals at high risk, with comorbidities or who are pregnant, the clinical symptoms of seasonal influenza can evolve to be serious 7,9,10,12 .…”