Baloxavir reduces symptom duration similarly to oseltamivir, primarily within 24 hours of symptom onset

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Published: 2019-09-09 © 2019 John Wiley & Sons, Inc.

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Clinical question
Is baloxavir a safe and effective for treatment of influenza?

Bottom line
Baloxavir has similar efficacy to oseltamivir (33-hour reduction in duration of symptoms compared with placebo), and like oseltamivir is most effective when given within 24 hours of the onset of symptoms. If given 24 to 48 hours after symptom onset, symptom duration was reduced by only13 hours (which is almost identical to what we found in our meta-analysis of oseltamivir [Fam Pract 2013;30(2):125-133]). It certainly does not seem worth the extra cost in the United States: $157 for baloxavir versus $40 for oseltamivir (, accessed July 28, 2019). There are no data regarding the effect on complications or mortality, nor any data for patients younger than 12 years, older than 64 years, or with serious comorbidities. The major advantages of baloxavir over oseltamivir for those who choose to use it are convenience, as it is only a single dose, and fewer adverse drug reactions (number needed to treat = 25). (LOE = 1b)

Hayden FG, Sugaya N, Hirotsu N, et al, for the Baloxavir Marboxil Investigators Group. Baloxavir marboxil for uncomplicated influenza in adults and children. N Engl J Med 2019;379(10):913-923.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Uncertain

Setting: Outpatient (any)

Baloxavir (Xofluza) inhibits polymerase acidic protein, which is involved in viral replication. This report summarizes the results of a phase 2 (dose-ranging) trial and a phase 3 trial comparing baloxavir with oseltamivir and placebo (baloxavir is now FDA approved). We will focus here on the phase 3 trial, which recruited patients aged 12 years to 64 years with an influenza-like illness (ILI) for less than 48 hours. The authors randomized the patients aged 20 years to 64 years into 1 of 3 groups in a 2:2:1 ratio: (1) baloxavir in a single dose (40 mg for patients weighing less than 80 kg, and 80 mg for patients weighing at least 80 kg), (2) oseltamivir 75 mg twice daily for 5 days, or (3) matching placebos. The patients aged 12 years to 19 years were randomized in a 2:1 ratio to baloxavir or placebo. ILI was defined as the presence of fever >= 38 C, at least one respiratory symptom that was moderately severe, and at least one systemic symptom. The median age of patients was 32 to 38 years among the different treatment groups, 77% of the patients were recruited in Japan (the remainder in the United States), and 53% were recruited within 24 hours of the onset of symptoms. Groups were fairly well balanced at randomization. Patients were followed up for 14 days, and the primary outcome was time to symptom alleviation, which was defined as all symptoms being absent or mild for at least 21.5 hours. Of the 1436 patients who were randomized, 1064 had influenza confimred by polymerase chain reaction (PCR). In the intention-to-treat population (patients with ILI), the median time to symptom alleviation was 88.6 hours for placebo and 65.4 hours for baloxavir (median difference 23.2 hours; 95% CI 14.0 - 34.2 hours). When limiting the analysis to only those who later were determined to have influenza by PCR, the median duration of symptoms was 80.2 hours for placebo, 53.7 hours for baloxavir, and 53.8 hours for oseltamivir. The benefit was much greater among patients recruited within 24 hours of onset of symptoms than in those recruited between 24 and 48 hours (32.8 hours vs 13.2 hours; P = .008). Nausea and vomiting were more common with oseltamivir (4.8%), diarrhea was more common with baloxavir (1.8%), but overall the drugs were well tolerated. The number needed to treat to prevent an adverse drug reaction with baloxavir compared with oseltamivir was 25.

Mark H. Ebell, MD, MS
University of Georgia
Athens, GA

Copyright © 2019 John Wiley & Sons, Inc.