Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data.

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu(®), Roche) treatment on mortality in patients with 2009A/H1N1 influenza. METHODS: We searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators' comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies. RESULTS: Effect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to 2.54%) and in households (oseltamivir RD 13.6%, 95% CI 9.52% to 15.47%; zanamivir RD 14.84%, 95% CI 12.18% to 16.55%). Oseltamivir increased psychiatric adverse events in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07% to 2.76%) and the risk of headaches while on treatment (RD 3.15%, 95% CI 0.88% to 5.78%). Effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza: Analysis of summary data of 30 studies as well as IPD of four studies showed evidence of time-dependent bias. After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65). CONCLUSIONS: Oseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children. Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza. Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households. The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002245. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Viral lung infections: epidemiology, virology, clinical features, and management of avian influenza A(H7N9).

PURPOSE OF REVIEW: The avian influenza A(H7N9) virus has jumped species barrier and caused severe human infections. Here, we present the virological features relevant to clinical practice, and summarize the epidemiology, clinical findings, diagnosis, treatment, and preventive strategies of A(H7N9) infection. RECENT FINDINGS: As of 18 February 2014, A(H7N9) virus has caused 354 infections in mainland China, Taiwan, and Hong Kong with a case-fatality rate of 32%. Elderly men were most affected. Most patients acquired the infection from direct contact with poultry or from a contaminated environment, although person-to-person transmission has likely occurred. A(H7N9) infection has usually presented with severe pneumonia, often complicated by acute respiratory distress syndrome and multiorgan failure. Mild infections have been reported in children and young adults. Nasopharyngeal aspirate and sputum samples should be collected for diagnosis, preferably using reverse transcriptase-PCR. Early treatment with neuraminidase inhibitors improved survival, but the efficacy of antivirals was hampered by resistant mutants. The closure of live poultry markets in affected areas has significantly contributed to the decline in the incidence of human cases. SUMMARY: The emergence of A(H7N9) virus represents a significant health threat. High vigilance is necessary so that appropriate treatment can be instituted for the patient and preventive measures can be implemented.

U.S. utilization patterns of influenza antiviral medications during the 2009 H1N1 influenza pandemic.

BACKGROUND: The 2009 H1N1 influenza pandemic in the United States occurred from April 2009 to April 2010. The 2009 H1N1 influenza virus was susceptible to neuraminidase inhibitors (oseltamivir and zanamivir). OBJECTIVES: To characterize the 2009 H1N1 influenza pandemic in the United States from April 2009 to April 2010 using weekly influenza antiviral prescription utilization data and the CDC's weekly reports of the number of visits for influenza-like-illnesses by the Influenza Sentinel Provider Surveillance Network. METHODS: A proprietary outpatient data source used by the FDA, which captures adjudicated U.S. prescription claims for select influenza antiviral drugs, was used to conduct this analysis. Data were extracted weekly and analyzed for surveillance during the pandemic. Results were compiled at the end of the pandemic. RESULTS: Oseltamivir has dominated the U.S. influenza antiviral market share of dispensed prescriptions since approval in October 1999 and was the primary influenza antiviral drug used during the 2009 H1N1 influenza pandemic. However, commercial availability of the suspension formulation of oseltamivir was reduced by high demand during the pandemic. Dispensed prescription trends of other influenza antiviral medications studied followed that those of oseltamivir, even antivirals for which the 2009 H1N1 strains showed resistance. CONCLUSION: Weekly prescription utilization of all influenza antivirals used to treat influenza during the seasonal influenza outbreak followed the same trend of weekly reports of the number of visits for influenza-like-illnesses (ILI) by the Influenza Sentinel Provider Surveillance Network. The ILI epidemic curve resembled dispensed antiviral prescription trends (both overall and stratified by age), providing some corroboration for the surveillance data.