Postexposure prophylaxis with baloxavir marboxil reduced influenza incidence in household contacts of patients diagnosed with influenza, according to a study from Japan.

“[The results] showed that rapid administration of single-dose baloxavir as postexposure prophylaxis was highly effective in preventing influenza in the household setting,” said the researchers. The efficacy of baloxavir applied to prevention of influenza as well as prevention of symptom development in those already infected, they noted.

During the 2018–2019 influenza season, 752 “well”* household contacts of 545 index patients (mean age 11.3 years, 53.2 percent male) with influenza were randomized 1:1 to receive one dose of oral baloxavir or placebo (mean age 33.5 and 33.6 years, respectively) and followed for 10 days. 

Index patients had been treated with baloxavir (52.7 percent), oseltamivir (31.4 percent), or another neuraminidase inhibitor (16.0 percent), 73.6 percent were aged<12 years, and 95.6 percent had influenza A infection. Seven and 9.6 percent of baloxavir and placebo recipients, respectively, had RT-PCR**-confirmed influenza at baseline.

Incidence of RT-PCR-confirmed influenza plus fever (axillary temperature ≥37.5°C) and ≥1 moderate or severe respiratory symptom up to day 10 was significantly reduced in baloxavir compared with placebo recipients (1.9 percent vs 13.6 percent; adjusted risk ratio [adjRR], 0.14, 95 percent confidence interval [CI], 0.06–0.30; p<0.001). [N Engl J Med 2020;383:309-320]

This reduced risk of RT-PCR-confirmed influenza infection was also evident regardless of symptoms (adjRR, 0.43, 95 percent CI, 0.32–0.58).

Baloxavir efficacy appeared consistent regardless of vaccination status, underlying risk factors, age of index patients, and influenza A virus subtypes. There was a suggestion of a greater benefit in patients aged ≥12 years compared with those aged <12 years (adjRR, 0.10 vs 0.27). Among patients with influenza at baseline, fewer baloxavir than placebo recipients developed influenza symptoms (19 percent vs 58 percent; adjRR, 0.34). 

Among baloxavir recipients, 10 patients had PA I38T/M variant viruses and five patients PA E23K variant viruses during or after prophylaxis. Four of these occurred before baloxavir treatment and four were related to index patients who had received a neuraminidase inhibitor. 

“[T]hese infections were likely initiated by wild-type virus with subsequent emergence of PA-substituted virus under the selective pressure of baloxavir.” While transmission of these variants from baloxavir-treated index patients to placebo recipients was undetected, transmission to baloxavir recipients cannot be ruled out, the researchers said. Furthermore, later emergence of these variants was not studied.

Two placebo recipients experienced PA I38T-substituted viruses following rescue treatment with baloxavir for influenza symptoms.

Adverse event (AE) incidence was similar in baloxavir and placebo recipients (22.2 percent vs 20.5 percent). Headache, haematuria, pharyngitis, and elevated alanine aminotransferase levels were the most frequently reported AEs. One haematuria incident was deemed baloxavir-related. One placebo recipient developed a serious AE (atypical psychosis).

What’s next?

There is some concern that “viruses with reduced susceptibility to baloxavir” could occur more often in baloxavir-treated children, said Dr Timothy Uyeki from the Centers for Disease Control and Prevention, Atlanta, Georgia, US, in an editorial. [N Engl J Med 2020;383:389-390]

This could potentially lead to, among other outcomes, prolonged illness and longer viral shedding. “Global surveillance is essential to monitor circulation of influenza viruses with reduced susceptibility to baloxavir,” he said.

Additionally, whether additional doses of baloxavir, be it as treatment or postexposure prophylaxis, could “reduce the emergence and transmission of influenza viruses with reduced susceptibility to baloxavir” remains to be seen, Uyeki concluded.

*no influenza symptoms and axillary temperature <37°C

**RT-PCR: Reverse-transcriptase–polymerase-chain-reaction