Favipiravir and oseltamivir combo better than monotherapy in severe influenza
China: Favipiravir and oseltamivir combination therapy is better than oseltamivir alone for the treatment of severe influenza, a recent study published in the Journal of Infectious Diseases has found.
Seasonal influenza results in the death of approximately 300,000 to 650,000 people each year. Oseltamivir, the neuraminidase inhibitor (NAI), the only drug in widespread use, is of limited use, and its efficacy for several cases have not been studied adequately. Adding an antiviral that works by a different mechanism might boost effectiveness, especially for the most compromised patients.
Favipiravir works differently from oseltamivir, targeting a viral RNA polymerase rather than the neuraminidase. Preclinical studies suggest synergy between favipiravir (Avigan, Toyama Chemical) and oseltamivir (Tamiflu, Genentech) as combination therapy to treat severe influenza, but the effectiveness of the drug combination has not been evaluated in controlled clinical trials.
Yeming Wang, from the Chinese Academy of Medical Sciences in Beijing, and colleagues compared findings from two prospective studies involving patients hospitalized for influenza: the "combination study" used both drugs, and the "monotherapy study" used only oseltamivir for patients who had community-acquired pneumonia and influenza.
Outcomes include the rate of clinical improvement, defined as a decrease of 2 categories on a 7-category ordinal scale, and viral RNA detectability over time. Sub-hazard ratio (sHR) was estimated by the Fine and Gray model for competing risks. In total, 40 patients were treated with combination therapy and 128 with oseltamivir alone.
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Key findings of the study include:
- Clinical improvement on Day 14 occurred in the combination group was higher than in the monotherapy group (62.5% vs 42.2%, p=0.0247).
- The adjusted sHR for combination therapy was 2.06.
- The proportion of undetectable viral RNA at day 10 was higher in the combination group than the oseltamivir group (67.5% vs 21.9%).
- No significant differences were observed in mortality or other outcomes.
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"Our findings suggest that favipiravir and oseltamivir combination therapy may be associated with greater antiviral effects and faster clinical improvement in severe influenza" than monotherapy, the researchers conclude. They suggest that a double-blinded, randomized controlled clinical trial be conducted to confirm the finding.
The dual-drug approach could address "the relatively high frequency of emergence of oseltamivir-resistant [viral] variants in critically ill patients and their association with poor outcomes," the researchers write. In addition, the results of the use of antibody-based therapies given with NAIs have been disappointing. Studies of other polymerase inhibitors (pimodivir and baloaxavir) given with NAIs to treat severe influenza in hospitalized patients are underway.
The study, "Comparative effectiveness of combined favipiravir and oseltamivir therapy versus oseltamivir monotherapy in critically ill patients with influenza virus infection," is published in The Journal of Infectious Diseases.
DOI: https://doi.org/10.1093/infdis/jiz656
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