Antivirals for nonsevere influenza

Background

The optimal antiviral drug treatment for patients with nonsevere influenza, defined as those who do not require hospitalization, is unclear. This study compared the effects of antiviral drugs for treating nonsevere influenza, including amantadine, baloxavir, favipiravir, laninamivir, oseltamivir, peramivir, umifenovir, and zanamivir.

Methods

Key databases were searched from inception to September 20, 2023, to identify randomized controlled trials comparing influenza antiviral drugs with placebo, standard care, or another antiviral drug in patients with nonsevere influenza who did not require hospitalization. The main outcomes were mortality, admission to hospital, admission to the intensive care unit, duration of hospitalization, time to alleviation of symptoms, emergence of resistance, and adverse events. The most common antiviral drug assessed was oseltamivir.

Results

The study included 73 trials, totaling 34,332 patients. When compared with a placebo or usual care, all antiviral drugs had little or no effect on mortality for low-risk patients and high-risk patients (high-certainty evidence).

For the outcome of hospitalization, all antiviral drugs had little or no effect in low-risk patients (high certainty; no data were available for amantadine and peramivir). In the high-risk group oseltamivir had little or no effect (risk difference [RD], −0.4%; 95% confidence interval [CI], −1.0 to 0.4; high certainty) and baloxavir may have reduced the risk (RD, −1.6%; 95% CI, −2.0 to 0.4; low certainty), with all the other drugs having little or uncertain effect.

For the outcome of time to symptom alleviation, baloxavir probably reduced symptom duration (mean difference [MD], −1.02 days; 95% CI, −1.41 to −0.63; moderate certainty), umifenovir may have reduced symptom duration (MD, −1.10 days; 95% CI, −1.57 to −0.63; low certainty), and oseltamivir probably had no important effect (almost certainly a reduction <1 day at best; MD, −0.75 days; 95% CI: −0.93 to −0.57; moderate certainty).

For treatment-associated adverse effects, baloxavir had few or no adverse events (RD, −3.2%; 95% CI: −5.2 to −0.6; high certainty), and oseltamivir probably increased adverse events (RD, 2.8%; 95% CI, 1.2-4.8; moderate certainty).

Conclusions

The authors concluded that in patients with nonsevere influenza baloxavir probably reduces the risk of hospitalization for the high-risk group and may reduce the time to symptom alleviation without increasing associated adverse effects. All the other antiviral drugs probably had little to no effect, or uncertain effects, on patient-important outcomes.

McMaster editors’ commentary

This is an important and revealing review that outlines the limitations of antiviral therapy in the majority of patients who present with flulike symptoms and are not sick enough to require hospitalization. The widespread use of oseltamivir (marketed as Tamiflu) and other antiviral drugs may reflect clinicians’ inclination to “do something” for their patients, while possibly downplaying the associated drug costs and their potential adverse effects. The old adages of lots of rest, fluids, and chicken soup may be very reasonable to follow.