The key starting place to consider which medications are efficacious is to recognize the bar for success for these antivirals is extraordinarily difficult to measure.  Absent antivirals, the chance of death from non-severe influenza was estimated at 1 in 5,000 in the low-risk cohort, and at 1 in 500 in the high-risk cohort.  Therefore, it is virtually impossible to measure a clinically meaningful effect on mortality.  Hospitalization rates are ten times greater however, and are the primary surrogate for efficacy relied upon in the included trials.

Getting straight to the main, practice-informing point of their findings: oseltamivir belongs on the junk heap.  Where these authors could generate evidence with high level of certainty, they were unable to find any signal oseltamivir reduced mortality or admission to hospital.  These findings were consistent across both low-risk and high-risk cohorts.  With respect to alleviation of symptoms, oseltamivir may decrease illness duration by a little more than half a day, but this outcome was uncertain due to serious risk of bias.  Likewise, oseltamivir may increase treatment-related non-serious adverse events, commonly nausea and vomiting, but this outcome is also affected by the same risk of bias.

The story is a bit different with baloxavir. Owing to the baseline low rate of mortality, baloxivir could not demonstrate a meaningful improvement in this outcome. Nevertheless, baloxivir did demonstrate a substantial effect on hospitalization and a full day’s worth of alleviation of symptoms.  The big caveat:  these outcomes are held with low and moderate certainty due to “serious imprecision”. This imprecision stems from a relative paucity of data on baloxavir, derived primarily from a mere three clinical trials sponsored by the manufacturer.

There is another important consideration for baloxavir:  resistance. In the studies included in this review, an estimated of ~10% of virus isolates demonstrated induced antiviral resistance following treatment with baloxavir.  While the controlled clinical trial evidence certainly favored baloxavir, widespread use during influenza season would likely attenuate this advantage and reduce its effectiveness during future seasons.³

The other antivirals mentioned are primarily used in overseas markets. In this review, the data regarding each was too sparse to suggest that any could yet be considered promising candidates to improve outpatient management of non-severe influenza.

So, what does “good prescribing” during influenza season look like?  In the vast majority of uncomplicated influenza managed as an outpatient, it ought to simply be recommendations for symptomatic self-care.  Oseltamivir has become ingrained in clinical practice, most likely as result of an initial favorable view arising from non-publication of early negative trials.^4,5 It is always more difficult to “de-adopt” practices than for them to take root.  On the other hand, baloxavir demonstrates obvious appeal.  However, baloxavir remains both costly from an individual standpoint, and damaging to public health from a population standpoint.  Where possible, baloxavir ought be prescribed conservatively in those at highest risk, as widespread use will ultimately become its downfall.