Neuraminidase inhibitors reduced mortality risk during H1N1 pandemic

Adults who received treatment with neuraminidase inhibitors for influenza A(H1N1)pdm09 during the 2009-2010 pandemic were 25% less likely to die of the disease, according to study results published in The Lancet Respiratory Medicine.

The researchers also found that receiving treatment within 2 days of the onset of influenza symptoms reduced the risk for death by half vs. later treatment or no treatment.

“Many governments have stockpiles of Tamiflu that are close to expiry,” Jonathan Nguyen-Van-Tam, DM, of the University of Nottingham in the United Kingdom, said in a press release. “But until now, they had no adequate data to assist them in deciding if lives were saved in 2009-2010 or not, and whether they should replenish or not. … The situation is made more complex by the fact that when an influenza pandemic occurs, even with the best will in the world, vaccine arrives 6 months too late and its public health benefit is therefore moderate at best.”

Nguyen-Van-Tam and colleagues from the Post-pandemic Review of anti-Influenza Drug Effectiveness (PRIDE) conducted a meta-analysis to evaluate whether neuraminidase inhibitors, primarily oseltamivir (Tamiflu, Genentech), had any effect on death among adult patients hospitalized with pH1N1 from Jan. 2, 2009, to March 14, 2011. They identified 78 studies in a systematic review, which included data for 29,324 patients who were hospitalized during this period.

They found that treatment with neuraminidase inhibitors reduced the mortality risk by 19%, regardless of the time during the illness they were treated (OR=0.81; 95% CI, 0.7-0.93). Treatment within 2 days of illness onset reduced mortality by 52% compared with later treatment (OR=0.48; 95% CI, 0.41-0.56.) Similarly, early treatment reduced mortality by 50% compared with no treatment at all (95% CI, 0.37-0.67).

The survival benefit extended to pregnant women and to adults with more severe symptoms in intensive care, the researchers found. No significant mortality reduction was found among children aged 0 to 15 years.

“Since placebo-controlled trials of [neuraminidase inhibitors] are not ethically feasible during a pandemic, the evidence we have assembled is likely to be the best that is available,” Nguyen-Van-Tam said. “Our data suggest that in line with [CDC] recommendations, treatment guidance policies should emphasize that [neuraminidase inhibitor] treatment should be started as soon as possible for any hospitalized adult who presents with influenza that is suspected or confirmed.”

In an accompanying editorial, Alicia Fry, MD, of the CDC, said the results emphasized that early treatment is optimal and treatment should not be delayed by even 1 day to wait for diagnostic test results. Treatment may still be effective more than 2 days after illness onset, but the benefit is unknown.

“Although additional evidence for the benefits of [neuraminidase inhibitor] treatment in children admitted to hospital, and how to optimize treatment, are needed, in the absence of any other influenza-specific treatment, the potential benefit from [neuraminidase inhibitor] treatment for severely ill children is substantial and outweighs any potential risk associated with treatment,” she wrote. “Continuing efforts to identify other anti-influenza treatment options, especially those with different virus targets or mechanisms of action, might improve our ability to care for severely ill patients with influenza and reduce the risk of mortality further.”

For more information:

Fry A. Lancet Respir Med. 2014;doi:10.1016/S2213-2600(14)70068-2.

Muthuri S. Lancet Respir Med. 2014;doi:10.1016/S2213-2600(14)70041-4.

Disclosure: The study was funded by F. Hoffmann-La Roche. Nguyen-Van-Tam reports various financial ties to several influenza vaccine and neuraminidase inhibitor manufacturers. See the study for a complete list.