IMPORTANCE: The optimal antiviral drug for treatment of nonsevere influenza remains unclear.
OBJECTIVE: To compare effects of antiviral drugs for treating nonsevere influenza.
DATA SOURCES: MEDLINE, Embase, CENTRAL, CINAHL, Global Health, Epistemonikos, and ClinicalTrials.gov were searched from database inception to September 20, 2023.
STUDY SELECTION: Randomized clinical trials comparing direct-acting influenza antiviral drugs to placebo, standard care, or another antiviral drug for treating people with nonsevere influenza.
DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently performed data extraction and risk of bias assessment. A frequentist network meta-analysis was performed to summarize the evidence and the certainty of evidence was evaluated using the GRADE approach.
MAIN OUTCOMES AND MEASURES: Mortality, admission to hospital, admission to the intensive care unit, duration of hospitalization, time to alleviation of symptoms, emergence of resistance, and adverse events.
RESULTS: Overall, 73 trials with 34?332 participants proved eligible. Compared with standard care or placebo, all antiviral drugs had little or no effect on mortality for low-risk patients and high-risk patients (all high certainty). All antiviral drugs (no data for peramivir and amantadine) had little or no effect on hospital admission for low-risk patients (high certainty). For hospital admission in high-risk patients, oseltamivir (risk difference [RD], -0.4%; 95% CI, -1.0 to 0.4; high certainty) had little or no effect and baloxavir may have reduced risk (RD, -1.6%; 95% CI, -2.0 to 0.4; low certainty); all other drugs may have had little or uncertain effect. For time to alleviation of symptoms, 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); oseltamivir probably had no important effect (MD, -0.75 days; 95% CI, -0.93 to -0.57; moderate certainty). For adverse events related to treatment, baloxavir (RD, -3.2%; 95% CI, -5.2 to -0.6; high certainty) had few or no adverse events; oseltamivir (RD, 2.8%; 95% CI, 1.2 to 4.8; moderate certainty) probably increased adverse events.
CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that baloxavir probably reduced risk of hospital admission for high-risk patients and may reduce time to alleviation of symptoms, without increasing adverse events related to treatment in patients with nonsevere influenza. All other antiviral drugs either probably have little or no effect, or uncertain effects on patient-important outcomes.
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Public Health | |
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Infectious Disease | |
This systematic review and meta-analysis in nonsevere influenza found that compared with standard care or placebo, all antiviral drugs had little or no effect on mortality in all patients and admission in low-risk patients. They did find that baloxavir may reduce risk of admission in high-risk patients and may reduce symptom duration. They found baloxavir had few or no adverse events, while oseltamivir likely increased adverse events. Unfortunately, there was significant heterogeneity and, ultimately, this meta-analysis demonstrates the low likelihood of benefit with several antiviral therapies in those with influenza. Clinicians should continue to recommend other therapies.
The two healthcare systems in which I've worked over the past 5 years only have oseltamivir on formulary, despite the controversies around the oseltamivir effectiveness trials and missing data as well as limited benefits in the best-case scenario (https://thesgem.com/2020/12/sgem312-oseltamivir-is-like-bad-medicine-for-influenza/ and https://thesgem.com/2023/07/sgem409-same-as-it-ever-was-tamiflu-for-influenza/). The results of this meta-analysis might compel emergency physicians to explore adding baloxavir to their formulary and move the needle on effective antiviral prescribing for influenza.
As an Internist treating patients with influenza, I found this article very useful for everyday clinical practice.
This review indirectly highlights the importance of vaccination in preventing hospitalization and death in higher-risk individuals. The fact that oseltamivir does not reduce admissions or mortality is an important reminder. Although baloxavir may reduce admissions in those at increased risk, it is much more costly than oseltamivir. Where clinically some may take exception with the findings in the short-term relief offered by antiviral meds, for anyone who has had influenza, the quicker improvement in symptoms is clinically relevant.
It would be interesting to see a cost-benefit analysis of these drugs. Probably not worth the money.
