Antivirals for Influenza

The upcoming issue of The Medical Letter leads off with an article on antiviral drugs for influenza, which could be considered an underused resource. Influenza isn’t COVID 19, but it often kills 30,000 people or more in a year, which is automobile accident and gunshot territory. Maybe this year widespread use of masks will limit the number of cases, but we can’t count on that.

How effective are the drugs, and how effective do they need to be for us to prescribe them freely? That has been a contentious issue for years in these pages. Given early, oseltamivir clearly reduces the duration of illness, but is that enough to justify spending millions of dollars to stockpile neuraminidase inhibitors in anticipation of a pandemic that may never come? We are all feeling the sting of a pandemic that did come, and an influenza pandemic once killed 50 million people, albeit in the wake of a devastating world war.

One of the difficulties in assessing the effectiveness of oseltamivir is the involvement of Roche in the clinical trials of Tamiflu, which is where most of the evidence comes from. A good example of that is a 2015 meta-analysis of 9 randomized controlled trials of oseltamivir in 4328 patients with influenza (J Dobson et al. Lancet 2015; 385:1729).  All of the data came from Roche-sponsored trials, but the manufacturer had no role in the design, conduct, or reporting of the meta-analysis. The median time for disappearance of symptoms, the primary outcome, was 97.5 hours with oseltamivir and 122.7 hours with placebo, a significant difference. Moreover, the incidence of lower respiratory tract complications requiring antibiotics was significantly reduced in oseltamivir-treated patients compared to the placebo group (4.9% vs 8.7%). Oseltamivir increased the risk of nausea (9.9% vs 6.2%) and vomiting (8.0% vs 3.3%), both significant differences.

Maybe Roche didn’t influence the outcome of the meta-analysis, but what about the original studies? Admittedly, there is no such thing as being too cynical. Does a smaller risk of lower respiratory infections translate into a smaller risk of dying? I think it probably does. Is this degree of nausea and vomiting too high a price to pay for these modest improvements in outcomes? I don’t think so. But that’s just one person’s opinion. Read our article and see what the experts recommend.

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