Effects of Baloxavir Marboxil Plus Neuraminidase Inhibitor vs Neuraminidase Inhibitor in High-risk Patients Hospitalized With Severe Influenza: A Post Hoc Analysis of the Flagstone Trial - Report - MDSpire
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Effects of Baloxavir Marboxil Plus Neuraminidase Inhibitor vs Neuraminidase Inhibitor in High-risk Patients Hospitalized With Severe Influenza: A Post Hoc Analysis of the Flagstone Trial
Baloxavir Plus Neuraminidase Inhibitors Reduce Mortality in High-risk Severe Influenza
Overview
In a post hoc analysis of the Flagstone trial, combining baloxavir with neuraminidase inhibitors (NAIs) in hospitalized high-risk patients with severe influenza significantly reduced 28-day mortality and accelerated viral clearance compared to NAI monotherapy. The combination was particularly effective in patients infected with influenza A H3N2, shortening time to clinical improvement without increasing adverse events.
Background
Severe influenza in high-risk populations such as immunocompromised individuals, diabetics, and those with chronic lung disease is associated with high morbidity and mortality. While antiviral monotherapies have shown benefits in nonsevere influenza, their efficacy in severe cases remains uncertain. Baloxavir, an influenza RNA polymerase inhibitor, has demonstrated superior viral clearance in uncomplicated influenza, suggesting potential benefits when combined with NAIs in severe cases. The Flagstone trial is the only randomized controlled study evaluating this combination in hospitalized patients with severe influenza.
Data Highlights
Outcome
Dual Antiviral Group (Baloxavir + NAI)
Mono Antiviral Group (NAI alone)
P value
Number of patients
92
51
Median Time to Clinical Improvement (hours) - Influenza A H3N2
97.53 (IQR 43.02–149.27)
172.42 (IQR 95.93–243.52)
0.013
28-day Mortality
2 (2.17%)
6 (11.76%)
0.02
Time to Cessation of Viral Shedding
Shorter
Longer
<0.001
Adjusted Mean Change in Virus Titer (Baseline to Day 2)
Greater Reduction
Less Reduction
<0.001
Serious Adverse Events
Comparable
Comparable
0.42
Key Findings
Combination therapy with baloxavir plus NAIs significantly reduced 28-day mortality compared to NAI monotherapy (2.17% vs 11.76%, P = .02).
In patients infected with influenza A H3N2, time to clinical improvement was significantly shorter with combination therapy (median 97.53 vs 172.42 hours, P = .013).
The dual antiviral group showed a significantly faster cessation of viral shedding (P < .001) and greater reduction in viral titers by day 2 (P < .001).
Serious adverse events were similar between combination and monotherapy groups, indicating no increased safety risk.
The study focused on high-risk hospitalized patients with immunosuppression, diabetes, or chronic lung disease, populations with impaired viral clearance and higher influenza mortality.
Clinical Implications
For hospitalized patients with severe influenza and high-risk conditions, combining baloxavir with neuraminidase inhibitors may offer a mortality benefit and faster viral clearance without added safety concerns. Clinicians should consider this combination therapy especially in patients infected with influenza A H3N2 subtype. This approach may optimize outcomes in populations with impaired viral clearance who are at elevated risk of severe disease.
Conclusion
Baloxavir combined with neuraminidase inhibitors provides superior mortality reduction and enhanced virological outcomes compared to neuraminidase inhibitor monotherapy in high-risk patients hospitalized with severe influenza. This combination represents a promising therapeutic strategy without compromising safety.
References
Flagstone Trial Post Hoc Analysis 2024 -- Impact of Combining Baloxavir Marboxil with Neuraminidase Inhibitors in Severe Influenza
