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Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza
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Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza

Review of recent systematic reviews and meta-analyses

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The neuraminidase inhibitors oseltamivir and zanamivir, currently authorised in the European Union/European Economic Area (EU/EEA) for treatment and prophylaxis of influenza disease (including seasonal, pandemic and zoonotic influenza), have been the subject of debate concerning their effectiveness and safety, and as a consequence, also the appropriateness of stockpiling these drugs for use in future influenza pandemics. In 2013, the ECDC Advisory Forum requested an assessment of the evidence for use of antivirals in influenza outbreak settings, specifically during institutional outbreaks and new and emerging influenza virus outbreaks. In August 2014, the EU Health Security Committee requested a review of the evidence, and on 10–11 February 2015, an expert consultation with international public health experts was convened in Stockholm to review data presented in newly conducted systematic reviews/meta-analyses of clinical studies on influenza antivirals, and in order to develop an ECDC expert opinion. Three large systematic reviews and meta-analyses assessing efficacy, effectiveness and safety of two licensed neuraminidase inhibitors, oral oseltamivir and inhaled zanamivir, were reviewed: The 2014 Cochrane Collaboration report (Jefferson et al.), the 2015 MUGAS study (Dobson et al.) and the 2014 PRIDE study (Muthuri et al.). Additional reviews and studies were considered where appropriate. The 2014 Jefferson et al. report describes a systematic review with meta-analyses of clinical study reports from published and unpublished randomised, placebo-controlled trials (RCTs) assessing treatment or prophylaxis with oseltamivir (20 trials) and zanamivir (26 trials) up to July 2013, most of which were conducted among otherwise healthy persons in the community with influenza-like illness during seasonal epidemics. The Dobson et al. review reported a meta-analysis of individual patient data of 12 RCTs assessing treatment of adults with oseltamivir. Eleven of these trials were also included in the Cochrane report. In the observational study by Muthuri et al. investigators assembled data directly from study sites, assessing the association between use of neuraminidase inhibitors and mortality in a meta-analysis of individual participant data from 29 234 patients (all ages). The data were collected in 78 study sites located in 38 countries with laboratoryconfirmed or clinically diagnosed pandemic influenza A(H1N1)pdm09 infection admitted to hospital. The reviews by Jefferson et al. and Dobson et al. conclude that, for adults, oseltamivir decreases the time to first alleviation of symptoms of influenza-like illness (ILI) by 16.8 hours (95% CI 8.4–25.1) and 17.8 hours (95% CI 27.1 to 9.3), respectively. The time to alleviation of all symptoms among the sub-population with laboratory confirmed influenza infection was decreased by 25.2 hours 95% CI 16.0–36.2) in the Dobson et al. analysis. Additional analyses within the Jefferson et al. and Dobson et al. reviews documented a statistically significant reduction in patient-reported pneumonia, a reduction in lower respiratory tract infections and a decrease in hospital admissions following influenza diagnosis among oseltamivir-treated groups. The individual RCTs included in these meta-analyses were not, however, designed or powered to assess these severe clinical outcomes, thus limiting the quality of evidence on such outcomes.
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