Literature

From Pages to Practice

By Jehan F. Chowdhury, DO

Published August 5, 2020

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Susan is a 68-year-old woman with a history of hypertension and type 2 diabetes. She lives with her grandchild, Jordan, who is 14 years old. Jordan and several of his friends at school have been diagnosed with influenza A, but Susan has not had an influenza vaccine this year. Her friends told her about a new medication that might prevent the flu after exposure. She asks her primary care physician about this medication. 

Baloxavir marboxil (baloxavir) was approved by the FDA in 2018 for the treatment of seasonal influenza A and B. The drug acts by inhibiting a cap-dependent endonuclease and interfering with viral mRNA synthesis. One dose within 2 days after the onset of illness shortens the duration of illness, but emergence of baloxavir-resistant viruses is a concern.

In a recent multicenter, double-blind, randomized, placebo-controlled trial published in NEJM, researchers evaluated the efficacy of a single dose of baloxavir for postexposure prophylaxis in 752 household contacts of 545 confirmed influenza cases. Baloxavir prophylaxis was given within 2 days of exposure. After close monitoring for influenza symptoms and positive tests, the percentage of patients who developed laboratory confirmed influenza was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%). Baloxavir was effective in high-risk patients, those under the age of 12 years, and unvaccinated subgroups and the overall safety profile was similar to that of placebo. Eleven of the 20 baloxavir recipients who tested positive for influenza had variant viruses with polymerase acidic protein substitutions.

Based on these results, baloxavir prophylaxis appears to be a safe and effective treatment option for high-risk patients like Susan to reduce the risk of contracting the flu after exposure. Susan should be reminded that annual influenza vaccination is the best protection. Ongoing monitoring of the emergence of baloxavir-resistant viruses is necessary.

The following NEJM Journal Watch summary further explains the study and findings:

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Baloxavir Can Prevent Influenza

Stephen G. Baum, MD reviewing Ikematsu H et al. N Engl J Med 2020 Jul 23 Uyeki TM. N Engl J Med 2020 Jul 23

Baloxavir marboxil (baloxavir) was FDA approved in 2018 for the treatment of seasonal influenza A and B. The drug acts through inhibition of a cap-dependent endonuclease, thereby interfering with viral mRNA synthesis. A single dose is as effective in shortening duration of illness as the recommended 5-day courses of twice-daily neuraminidase inhibitors. However, baloxavir-resistant viruses have emerged that are 10 to 420 times less susceptible than wild-type viruses. The variant viruses had amino acid substitutions in the polymerase acidic protein (PA). 

In a multicenter, double-blind, randomized, placebo-controlled study, researchers in Japan evaluated the protective effect of a single dose of baloxavir versus placebo in 752 household contacts of 545 confirmed cases. Prophylaxis was begun within 2 days after exposure (72.5% within 1 day). Participants were followed for new influenza symptoms or positive rapid tests for 10 days. Most index patients (73.6%) but only 19.0% of contacts were younger than 12 years. Of the index cases, 95.6% had influenza A.

Laboratory-confirmed influenza was seen in 1.9% of the baloxavir group versus 13.6% of the placebo group. For baloxavir recipients who did develop influenza, onset was delayed compared with placebo recipients. Efficacy of baloxavir was somewhat lower in those younger than 12 years. Among 20 baloxavir prophylaxis recipients who tested positive for influenza, 11 had variant viruses with PA substitutions These isolates were susceptible to neuraminidase inhibitors when used. 

Comment: Baloxavir administered prophylactically to household contacts of confirmed influenza cases appears effective in preventing influenza. As an editorialist notes, baloxavir also reduces viral load in the respiratory tract, which may dampen transmission from an index case, but for prophylaxis probably must be taken within 2 days after exposure, limiting the usefulness of this approach in the U.S. As the editorialist also states, vaccination against seasonal flu strains is the best protection against infection.

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Jehan is a 2020-2021 NEJM Editorial Fellow and an Infectious Disease physician. She completed her Infectious Disease fellowship at Tufts Medical Center.