Editor's Note
January 13, 2025
The Limited Role for Antiviral Therapy in Influenza
Jonathan D. Baghdadi, Deborah Grady, Daniel J. Morgan
JAMA Intern Med. Published online January 13, 2025. doi:10.1001/jamainternmed.2024.7258
Influenza is associated with substantial morbidity and mortality. Given this, antiviral therapy is commonly prescribed in an effort to prevent these outcomes. We therefore found it surprising that antivirals seem to make little difference for individuals with influenza in outpatient settings, even in the optimized setting of randomized clinical trials.1
Guidance from the US Centers for Disease Control and Prevention and others generally encourage treatment of influenza with antivirals.2 For outpatients with risk factors, as well as their household contacts, antiviral therapy is recommended on the basis that it might help. For outpatients without risk factors, antiviral therapy may nonetheless be prescribed based on clinical judgment. In either case, pressure to start treatment as early as possible means that antivirals are often prescribed without diagnostic testing for influenza or thoughtful consideration of their benefits and risks.
Gao et al1 provide evidence that questions the current approach. In a large systematic review and meta-analysis of multiple clinical trials of outpatients with influenza, they found that oseltamivir causes more adverse effects (primarily nausea and vomiting) but has little to no effect on relevant clinical outcomes compared with placebo. Baloxavir marboxil, which is used less frequently, has minimal adverse effects and may reduce the duration of symptoms by 1 day, but increases the risk of antiviral resistance. Thus, baloxavir marboxil may be preferable when treatment is needed, but use may diminish effectiveness over time.
Both oseltamivir and baloxavir marboxil may have significant out-of-pocket costs for patients. Oseltamivir is covered by most insurance plans but may require a substantial co-pay. Baloxavir marboxil is less frequently covered by insurance and is typically more expensive than oseltamivir. No generic form of baloxavir marboxil is available.
When considering the evidence, we are left to wonder why reflexive treatment of influenza with oseltamivir has become so ingrained in clinical practice. One explanation is initial publication bias arising from nonpublication of early negative trials.3 We also think that action bias, or the tendency to do something even when the potential benefits are unclear, could be driving unnecessary use. Regardless, the accumulating evidence indicates that the time has come for clinicians and health care systems to reconsider their basic approach to outpatients with influenza.
