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Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts.
N Engl J Med. 2020 07 23; 383(4):309-320.NEJM

Abstract

BACKGROUND

Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear.

METHODS

We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018-2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed.

RESULTS

A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P<0.001). Baloxavir was effective in high-risk, pediatric, and unvaccinated subgroups of participants. The risk of influenza infection, regardless of symptoms, was lower with baloxavir than with placebo (adjusted risk ratio, 0.43; 95% CI, 0.32 to 0.58). The incidence of adverse events was similar in the two groups (22.2% in the baloxavir group and 20.5% in the placebo group). In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively. No transmission of these variants from baloxavir-treated index patients to participants in the placebo group was detected; however, several instances of transmission to participants in the baloxavir group could not be ruled out.

CONCLUSIONS

Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza. (Funded by Shionogi; Japan Primary Registries Network number, JapicCTI-184180.).

Authors+Show Affiliations

From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).From Ricerca Clinica, Fukuoka (H.I.), and Shionogi, Osaka (K.K., M.K., S.T., T.N., K.T., T.U.) - both in Japan; the Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville (F.G.H.); the Department of Medical Microbiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (M.D.J.); and the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Canada (N.L.).

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32640124

Citation

Ikematsu, Hideyuki, et al. "Baloxavir Marboxil for Prophylaxis Against Influenza in Household Contacts." The New England Journal of Medicine, vol. 383, no. 4, 2020, pp. 309-320.
Ikematsu H, Hayden FG, Kawaguchi K, et al. Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts. N Engl J Med. 2020;383(4):309-320.
Ikematsu, H., Hayden, F. G., Kawaguchi, K., Kinoshita, M., de Jong, M. D., Lee, N., Takashima, S., Noshi, T., Tsuchiya, K., & Uehara, T. (2020). Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts. The New England Journal of Medicine, 383(4), 309-320. https://doi.org/10.1056/NEJMoa1915341
Ikematsu H, et al. Baloxavir Marboxil for Prophylaxis Against Influenza in Household Contacts. N Engl J Med. 2020 07 23;383(4):309-320. PubMed PMID: 32640124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts. AU - Ikematsu,Hideyuki, AU - Hayden,Frederick G, AU - Kawaguchi,Keiko, AU - Kinoshita,Masahiro, AU - de Jong,Menno D, AU - Lee,Nelson, AU - Takashima,Satoru, AU - Noshi,Takeshi, AU - Tsuchiya,Kenji, AU - Uehara,Takeki, Y1 - 2020/07/08/ PY - 2020/7/9/pubmed PY - 2020/8/7/medline PY - 2020/7/9/entrez SP - 309 EP - 320 JF - The New England journal of medicine JO - N Engl J Med VL - 383 IS - 4 N2 - BACKGROUND: Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018-2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed. RESULTS: A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P<0.001). Baloxavir was effective in high-risk, pediatric, and unvaccinated subgroups of participants. The risk of influenza infection, regardless of symptoms, was lower with baloxavir than with placebo (adjusted risk ratio, 0.43; 95% CI, 0.32 to 0.58). The incidence of adverse events was similar in the two groups (22.2% in the baloxavir group and 20.5% in the placebo group). In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively. No transmission of these variants from baloxavir-treated index patients to participants in the placebo group was detected; however, several instances of transmission to participants in the baloxavir group could not be ruled out. CONCLUSIONS: Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza. (Funded by Shionogi; Japan Primary Registries Network number, JapicCTI-184180.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/32640124/Baloxavir_Marboxil_for_Prophylaxis_against_Influenza_in_Household_Contacts_ DB - PRIME DP - Unbound Medicine ER -