Severe influenza: is there a role for antiviral combinations?

Neuraminidase inhibitors have been approved for over 20 years and are currently the standard of care for the treatment of influenza. However, meta-analyses have shown only modest benefit of neuraminidase inhibitors for influenza. 1 Dobson J Whitley RJ Pocock S Monto AS Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015; 385: 1729-1737 Summary Full Text Full Text PDF PubMed Scopus (361) Google Scholar , 2 Muthuri SG Venkatesan S Myles PR et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med. 2014; 2: 395-404 Summary Full Text Full Text PDF PubMed Scopus (457) Google Scholar New treatment strategies for severe influenza are urgently required. A novel antiviral, baloxavir marboxil (baloxavir hereafter), was first approved in Japan in 2018, and subsequently in other countries. Baloxavir belongs to a new class of antivirals that inhibit the endonuclease function of the polymerase acidic protein. 3 O'Hanlon R Shaw ML Baloxavir marboxil: the new influenza drug on the market. Curr Opin Virol. 2019; 35: 14-18 Crossref PubMed Scopus (69) Google Scholar In a 2018 clinical trial, 4 Hayden FG Sugaya N Hirotsu N et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018; 379: 913-923 Crossref PubMed Scopus (407) Google Scholar a single dose of baloxavir produced greater reductions in influenza viral load than did oseltamivir, with equivalent time to symptom alleviation. Combining baloxavir marboxil with standard-of-care neuraminidase inhibitor in patients hospitalised with severe influenza (FLAGSTONE): a randomised, parallel-group, double-blind, placebo-controlled, superiority trialCombining baloxavir with NAIs did not result in superior clinical outcomes compared with NAIs alone. The combination of baloxavir plus NAI was well tolerated. The findings suggest that combination antivirals would not be routinely indicated in clinical practice for hospitalised patients with severe influenza. Full-Text PDF